Both parents are carriers of a mutation (because they are not sick and have already had a homozygous child), and the next offspring has a 50% chance of receiving the mutation from each parent, so the probability of receiving it from both is 50%x50%=25%.

A couple with a first male child (index case) with cystic fibrosis (mucoviscidosis) come for genetic counseling. Molecular diagnosis indicates that the index case is homozygous for the F5O8del mutation and his parents are heterozygous carriers. The clinical geneticist will inform them about the mode of transmission of the disease. Which statement is correct?

The probability that the next offspring will be affected is 25%.

The probability that the next offspring will be affected is 50%.

Having had an affected child, the next offspring will also be affected.

Having had a homozygous F5O8del child, the next offspring will be heterozygous carriers (67%) or homozygous genotype without the mutation (33%).

Bayes' theorem

Using genetic test results Parental genetic testing can detect around 90% of known disease alleles in parents that can lead to carrier or affected status in their child. Cystic fibrosis is a heritable disease caused by an autosomal recessive mutation on the CFTR gene, located on the q arm of chromosome 7. Bayesian analysis of a female patient with a family history of cystic fibrosis (CF), who has tested negative for CF, demonstrating how this method was used to determine her risk of having a child born with CF: Because the patient is unaffected, she is either homozygous for the wild-type allele, or heterozygous. To establish prior probabilities, a Punnett square is used, based on the knowledge that neither parent was affected by the disease but both could have been carriers: Given that the patient is unaffected, there are only three possibilities. Within these three, there are two scenarios in which the patient carries the mutant allele. Thus the prior probabilities are ⅔ and ⅓.

InternalMed_Harrison

In most instances, an affected individual is the offspring of heterozygous parents. In this situation, there is a 25% chance that the offspring will have a normal genotype, a 50% probability of a heterozygous state, and a 25% risk of homozygosity for the recessive alleles (Figs. 82-10, 82-13B). In the case of one unaffected heterozygous and one affected homozygous parent, the probability of disease increases to 50% for each child. In this instance, the pedigree analysis mimics an autosomal dominant mode of inheritance (pseudodominance). In contrast to autosomal dominant disorders, new mutations in recessive alleles are rarely manifest because they usually result in an asymptomatic carrier state.

Bayes' theorem

Next, the patient undergoes genetic testing and tests negative for cystic fibrosis. This test has a 90% detection rate, so the conditional probabilities of a negative test are 1/10 and 1. Finally, the joint and posterior probabilities are calculated as before. After carrying out the same analysis on the patient’s male partner (with a negative test result), the chances of their child being affected is equal to the product of the parents' respective posterior probabilities for being carriers times the chances that two carriers will produce an affected offspring (¼).

Obligate carrier

Autosomal Recessive In an autosomal recessive disease, if an individual is heterozygous for the mutant allele, they are a carrier because the disease is recessive. If homozygous, they have the disease. All offspring of an affected individual are either heterozygous or homozygous for the mutated allele. Consequently, all unaffected (heterozygous) offspring of an affected individual are obligate carriers of the disease because they will necessarily carry the mutated allele. Detection

Lethal allele

Types of lethal allele Recessive lethals A pair of identical alleles that are both present in an organism that ultimately results in death of that organism are referred to as recessive lethal alleles. Though recessive lethals may code for dominant or recessive traits, they are only fatal in the homozygous condition. Heterozygotes will sometimes display a form of diseased phenotype, as in the case of achondroplasia. One mutant lethal allele can be tolerated, but having two results in death. In the case of homozygous achondroplasia, death almost invariably occurs before birth or in the perinatal period. Not all heterozygotes for recessive lethal alleles will show a mutant phenotype, as is the case for cystic fibrosis carriers. If two cystic fibrosis carriers have children, they have a 25 percent chance of producing offspring having two copies of the lethal allele, eventually resulting in the death of the child.

Transmission disequilibrium test

We first describe the TDT in the case where families consist of trios (two parents and one affected child). Our description follows the notations used in Spielman, McGinnis & Ewens (1993). The TDT measures the over-transmission of an allele from heterozygous parents to affected offsprings. The n affected offsprings have 2n parents. These can be represented by the transmitted and the non-transmitted alleles and at some genetic locus. Summarizing the data in a 2 by 2 table gives: The derivation of the TDT shows that one should only use the heterozygous parents (total number b+c). The TDT tests whether the proportions b/(b+c) and c/(b+c) are compatible with probabilities (0.5, 0.5). This hypothesis can be tested using a binomial (asymptotically chi-square) test with one degree of freedom: Outline of the test derivation

Impact of genetic testing and family health history of cystic fibrosis in the early prenatal diagnosis and prevention of a new case of genetic disorder.

Cystic fibrosis (CF) is a multi-system autosomal recessive disorder, results of mutations in the CF transmembrane conductance regulator (CFTR) gene, located on the long arm of chromosome 7. We present a special family couple with particular medical history of CF, who comes to our Clinic for genetic tests and a prenatal genetic counseling, to prevent the birth of a new affected CF child. Genetic analysis showed that the first affected child, a daughter, is compound heterozygous for two clinically significant recessive mutations: c.1521_1523delCTT; p.Phe508del, inherited from her mother, who carries the same CFTR mutation, and c.1853_1863delTTTTGCATGAA; p.IIe618Argfs 2, inherited from her father, who is heterozygous, healthy carrier, for the same CFTR mutation. In our case report, early prenatal genetic testing, pre- and post-test genetic counseling was crucial in the management of the present pregnancy, to prevent the birth of a new affected CF child.

[Genetic counseling in cystic fibrosis].

Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

Genetics, Autosomal Recessive -- Mechanism

The most common situation of an autosomal recessive disease occurs when the parents are each carrier or heterozygous (Dd). Children of carrier parents have a 25% chance of inheriting the disorder. This value is obtained by using the Punnet square model used in genetics. Each parent has a 50% chance of passing on the disease allele. Using the multiplication rule of probability, there is a 50% chance that the father passes on his disease allele and a 50% chance that the mother passes on her disease allele; 50% x 50% = 25%. So with the mating of carrier parents, there is a 25% chance that the child will be affected, a 50% chance that the child would be a carrier, and 25% chance that they would be homozygous dominant and unaffected.

Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols.

Congenital bilateral absence of vas deferens (CBAVD) is a manifestation of the mildest form of cystic fibrosis (CF) and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator (CFTR) gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach: (i) first, a reverse dot-blot analysis was performed to detect mutations with regional impact; (ii) next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and (iii) finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%.

Carrier risk calculations for recessive diseases when not all the mutant alleles are detectable.

The number of recessive diseases, such as cystic fibrosis, in which some but not all of the mutations causing the disease can be detected using genetic probes, is certain to increase. For counselling purposes, the probability that a consultand known not to have a detectable mutation is nevertheless a carrier, needs to be calculated with as much accuracy as possible. This paper describes a program, available from the author, written specifically to make these calculations. As an example, results are presented for cystic fibrosis, assuming an incidence of 1 in 2,400 and that 80% of the mutations, being delta F508 mutations, are detectable. Numerical results are given when information may be available on the parents, one or two sibs and one or two children of the consultand. When test results are available on the children, the test status of the spouse of the consultand is relevant and may also be available. Risk calculations are also presented when an aunt (uncle) of the consultand has cystic fibrosis. Finally, disease and carrier risks are given for the child of first cousins, neither of whom has a detectable mutation.

Fibrodysplasia ossificans progressiva

A mutation in the gene ACVR1 (also known as activin-like kinase 2 (ALK2)) is responsible for the disease. ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes substitution of codon 206 from arginine to histidine in the ACVR1 protein. This substitution causes abnormal activation of ACVR1, leading to the transformation of connective tissue and muscle tissue into a secondary skeleton. This causes endothelial cells to transform to mesenchymal stem cells and then to bone. Genetics FOP is an autosomal dominant disorder. Thus, a child of an affected heterozygous parent and an unaffected parent has a 50% probability of being affected. Two affected individuals can produce unaffected children. Two unaffected individuals can produce an affected offspring as a result of the mutation of the gene. The homozygous dominant form is more severe than the heterozygous form.

Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues.

Screening for mutations in the entire Cystic Fibrosis gene (CFTR) of Brazilian infertile men with congenital absence of vas deferens, in order to prevent transmission of CFTR mutations to offspring with the use of assisted reproductive technologies. Specific polymerase chain reaction (PCR) primers were designed to each of the 27 exons and splicing sites of interest followed by single strand conformational polymorphism and Heteroduplex Analysis (SSCP-HA) in precast 12.5% polyacrylamide gels at 7 masculineC and 20 masculineC. Fragments with abnormal SSCP migration pattern were sequenced. Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in hetrozygosis. The available screenings for CF mutations do not include the atypical mutations associated to absence of vas deferens and thus, when these tests fail to find mutations, there is still a genetic risk of affected children with the help of assisted reproduction. We recommend the screening of the whole CFTR gene for these infertile couples, as part of the work-up before assisted reproduction.

Mutations at more than one locus may be involved in cystic fibrosis--evidence based on first-cousin data and direct counting of cases.

Cystic fibrosis was present in 35 of 5,265 first cousins of index cases with the disease. The gene frequency was estimated to be .0281 +/- .00544, using an improved method that allows for the influence of cousin sibship size upon the estimate. This figure is higher than that obtained by direct counting of cases in Victoria, Australia, from 1955-1979 (.0198 +/- .000127), raising the possibility that multiple gene loci may be involved in this disease. Further analysis showed that the number of affected first cousins fitted very well with an expected number based on a model involving two gene loci, each responsible for half the cases of cystic fibrosis. Agreement with expectations based on a single locus was not good. An alternate explanation of gross underascertainment of cases is dismissed because the index sibships were shown to fit very closely a truncate binomial distribution. The gene frequencies at the putative two loci would then each be .0140 and heterozygote frequencies one in 36. One in 18 people would be heterozygous at either one or the other of the loci.

Genetic, andrological and clinical characteristics of patients with congenital bilateral absence of the vas deferens.

The possibility of retrieving spermatozoa from the epididymis allows patients with congenital bilateral absence of the vas deferens (CBAVD) to father a child by means of assisted reproduction techniques. This has, however, increased the chance of transmitting a mutated allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene which increases the risk of generating offspring with cystic fibrosis (CF). Because of the increased heterogeneity of the CFTR locus, the study of a discrete number of mutations, as usually carried out in a diagnostic work-up, is unable to ascertain the presence of a mutation in a relatively high proportion of the patients screened. In an attempt to increase the chance of detecting the presence of CFTR gene abnormalities, 37 patients with CBAVD and one patient with congenital unilateral agenesis of the vas deferens (CUAVD) underwent an enlarged diagnostic protocol, which included screening for the most expected mutations of the CFTR gene in our population, evaluation of the five thymidine (5T) allelic variant, sweat test, respiratory function tests, evaluation of steatocrit, and an accurate evaluation of the history of the patient to search for symptoms commonly found in patients with CF. A single CFTR gene mutation was found in 18 patients (48.6%) with CBAVD and in the patient with CUAVD. The most frequent mutation observed was the Delta F508. Eleven patients (45.8%) had the 5T variant and in five of them it was not associated with any detectable mutation of the CFTR gene. Two female partners were found to be carriers of a mutation, whereas 5 (18.5%) had the 5T variant. As many as 71% of CBVAD patients had the simultaneous presence of at least two signs and/or symptoms suggestive of CF, albeit they were of mild intensity and the patients felt fit and healthy. In conclusion, these results suggested that some patients with CBAVD without CFTR gene mutation or 5T variant, even when their sweat test is negative, may show clinical suspicion of carrying a CFTR gene mutation and therefore are at risk of generating children affected by CF if the partner carries a mutation as well. The screening for mutations and a careful clinical examination may contribute to better identification of patients with CFTR-related CBAVD.

Albinism -- Treatment / Management -- Management of the Inheritable Nature of the Condition

Genetics consultation before childbearing years is beneficial to parents of albino children considering future offspring, the patient with albinism and their siblings. Albinism is an obligate homozygote condition with a 100% chance of passing on their defective gene. Coordinated genetic testing of the nonaffected partner is possible if the pathogenic variant is known. This will confirm the offspring have the potential to inherit the condition, if the partner is a carrier of the same pathogenic variant, or just be obligate carriers if the partner has only wild-type genes. A couple who has already had an albino child has a 25% chance of having another child with albinism, a 50% chance of producing carrier offspring, and 25% of producing non-carrier offspring. This is assuming that one of the parents is not albino, in which case the chance of producing a second albino offspring is 50% after a confirmed albino offspring. The fact than non-albino siblings have a 67% chance of being carriers is important to convey before they consider childbearing. Of note, if two parents carry genes for different types of albinism (for example, a patient with OCA2 and a carrier for OCA1), no children will be born with albinism, but the children are at risk for being heterozygous for both mutant alleles.

Multiple endocrine neoplasia

MEN1 mutations in multiple endocrine neoplasia patients and clinical genetics MEN1 gene mutations can be identified in 70-95% of MEN1 patients and in about 20% of familial isolated hyperparathyroidism cases. Almost all patients are heterozygous for mutations. One affected family has been identified with individuals both homozygous and heterozygous for MEN1 mutations. In this family, there was no difference in disease history between the homozygous and heterozygous mutation carriers. 50% of patients develop signs and symptoms by 20 years of age and more than 95% have symptoms by 40 years of age. There is significant intra- and inter-familial variability in the age of onset, the severity of disease, and tumor types. Despite numerous studies, no genotype-phenotype correlations have been established, suggesting that unknown genetic and environmental modifiers are involved in the expression of the MEN1 phenotype.

Cystic fibrosis screening: lessons learned from the first 320,000 patients.

To examine the data from > 335,000 Cystic fibrosis (CF) tests to detect unsuspected findings and obtain clinical data when indicated to optimize genetic counseling. A proprietary database containing 335,204 consecutive CF DNA tests and 445 CF prenatal diagnostic tests was queried. Clinical information was obtained for prenatal and selected nonprenatal cases by telephone contact with physician offices. The mutation 1078delT was found in much lower frequency than expected with rates of only 1:55,867 tests and 0.06% of CF mutations. This level is below the threshold set by the American College of Medical Genetics. Homozygosity was observed for 2789+5G>A in a 29-year-old women and compound heterozygosity with delta F408 in a 40-year-old woman with isolated chronic sinusitis. Many patients elected prenatal diagnosis when not at a 1:4 risk due to echogenic bowel or IVS-8 5T issues. With the exception of 1078delT, all CF mutations in the ACMG panel were detected with a frequency of > 0.1% of CF chromosomes. When ACMG guidelines are strictly adhered to, population-based CF carrier screening will accurately identify couples at risk for having children with CF.

Chondrodystrophy

Percentage risk of inheritance Both average parents''' A couple already has a child with chondrodystrophy; the risk of inheritance for the next child to have the disorder is 0.1% (less than 1 in 1,000) The risk that the normal-statured child will have at least one offspring with this disorder is 0.01% (less than 1 in 10,000) One parent with chondrodystrophy and one parent without One child with normal height; the probability of that child having offspring with chondrodystrophy is 0.01% (less than 1 in 10,000) One child with normal stature; the probability of the next having chondrodystrophy is 50% (1 in 2) One child with normal stature; the probability of the next not having chondrodystrophy is 50% (1 in 2) Both parents with chondrodystrophy The probability of offspring affected by chondrodystrophy is 100% (4 in 4) The probability of offspring to be of normal size is 0% (0 in 4)

Cystic fibrosis phenotype evaluation and paternity outcome in 50 males with congenital bilateral absence of vas deferens.

Most infertile males with congenital bilateral absence of vas deferens (CBAVD) carry mutations on the cystic fibrosis transmembrane conductance regulator gene and may express mild cystic fibrosis (CF) symptoms. Barriers to paternity for these men can now be overcome by assisted reproduction. Our aims were to investigate the CF-related phenotype and clinical outcome for 50 patients with CBAVD seen at a CF adult centre between 1992 and 1999. The investigation of the patients included screening for 22 CF mutations and identification of the poly-T variant of intron 8, sweat testing, clinical investigation for CF-related extra-genital manifestations, and genetic counselling. CFTR mutations were detected on 56 alleles of the 50 patients. A total of 15 (30%) was compound heterozygote and 26 (52%) heterozygote. In all, 38% of the patients had a positive sweat test. Four patients were diagnosed with typical CF not detected previously. Twenty-one patients became fathers following ICSI (eight cases), artificial insemination by donor or IVF with sperm donor (seven cases) or through adoption (six cases). A mail survey allowed the identification of CF-related clinical symptoms. Information on the occurrence of CF-related symptoms was obtained for 58.5% of patients: in the absence of initial symptoms, no new clinical signs were reported. Patients diagnosed with CBAVD need genetic counselling before assisted reproduction. Even when no wish for paternity is expressed, CF gene screening should be associated with at least a sweat test and clinical evaluation because of possible mild forms of CF disease. Medical follow-up did not reveal any new symptoms.

Gitelman syndrome

Epidemiology Gitelman syndrome is estimated to have a prevalence of 1 in 40,000 homozygous people . The ratio of men to women affected is 1:1. This disease is encountered typically past the 1st decade of life, during adolescence or adulthood but can occur in the neonatal period. Heterozygous carriers of the SLC12A3 gene mutations are 1% of the population. Parents with Gitelman syndrome have a low probability of passing the disorder to their offspring roughly 1 in 400 unless they are both carriers of the disease. History The condition is named for Hillel Jonathan Gitelman (1932– January 12, 2015), an American nephrologist working at University of North Carolina School of Medicine. He first described the condition in 1966, after observing a pair of sisters with the disorder. Gitelman and his colleagues later identified and isolated the gene responsible (SLC12A3) by molecular cloning. References External links "Gitelman syndrome". MedlinePlus. U.S. National Library of Medicine.

Reproductive decision making of aunts and uncles of a child with cystic fibrosis: genetic risk perception and attitudes toward carrier identification and prenatal diagnosis.

This paper evaluates the perceived genetic risk, the perceived burden, the impact on reproductive decision making, and the attitudes of aunts and uncles of a child with cystic fibrosis toward carrier identification, prenatal diagnosis, and pregnancy termination. A mailed questionnaire was sent to the aunts and uncles of 32 CF children (1) who attended the Paediatric Department of the University Hospital and (2) whose parents agreed to give the names and addresses of their sibs. The results for the 109 respondents aged less than 40 years are discussed. About one-fourth of them was aware of the "approximate" level of the risk to be a carrier of the CF gene and/or of the risk of having a CF child themselves. Nevertheless the subjective evaluation of the genetic risk has played a part in the reproductive decision-making process of at least 39% of the respondents. About three-fourths would (probably) make use of heterozygote detection and would (probably) ask for prenatal diagnosis should they become pregnant. It is striking that less than half of the group would interrupt the pregnancy should the fetus be affected. The intention to use prenatal diagnosis was significantly correlated with age and educational level while the acceptance of pregnancy interruption was significantly correlated with perceived burden, respondents' age, and health situation of the proband.

Germline mutation

Cystic fibrosis is an autosomal recessive disorder that causes a variety of symptoms and complications, the most common of which is a thick mucus lining in lung epithelial tissue due to improper salt exchange, but can also affect the pancreas, intestines, liver, and kidneys. Many bodily processes can be affected due to the hereditary nature of this disease; if the disease is present in the DNA of both the sperm and the egg, then it will be present in essentially every cell and organ in the body; these mutations can occur initially in the germline cells, or be present in all parental cells. The most common mutation seen in this disease is ΔF508, which means a deletion of the amino acid at the 508 position. If both parents have a mutated CFTR (cystic fibrosis transmembrane conductance regulator) protein, then their children have a 25% of inheriting the disease. If a child has 1 mutated copy of CFTR, they will not develop the disease, but will become a carrier of the disease. The

Dopamine transporter deficiency syndrome

DTDS is inherited in an autosomal recessive pattern, which means, for affected individuals, both copies of the gene in each cell have SLC6A3 mutations. As such, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and 25% chance of being unaffected and not a carrier. Once a SLC6A3 pathogenic variant is identified within an affected family member, carrier testing for at-risk relatives and prenatal testing or preimplantation genetic diagnosis for pregnancies can be options considered for genetic counseling. Diagnosis Diagnosis of SLC6A3-negative DTDS is established in a proband via molecular genetic testing, looking for biallelic (i.e. homozygous or compound heterozygous) pathogenic SLC6A3 variants. DTDS-positive patients are further identified by matching their genetic testing results with known characteristic clinical, laboratory, and imaging findings.

Relevance of genetic counselling in couples prior to intracytoplasmic sperm injection.

Since the first reports of successful pregnancies after treatment with intracytoplasmic sperm injection (ICSI) in humans numerous attempts have been made to assess the genetic risks of this highly invasive technique. During the study period (February 1995-November 96), 142 couples were referred to our genetic counselling unit prior to ICSI. In three couples, genetic counselling revealed a high recurrence risk for a monogenic disease (myotonic dystrophy, hereditary ataxia and polycystic kidney disease). In nine out of 128 men (7%) an abnormal karyotype was identified, including three Robertsonian translocations, two reciprocal translocations, three sex chromosome aberrations and one case with centric fission of chromosome no. 7. A total of 14 men refused chromosomal analysis. Only one of the 122 women examined had an abnormal karyotype (47, XXX). Five out of six men with congenital bilateral absence of the vas deferens (CBAVD) had at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Three had mutations in both CFTR alleles, including one case in which the second mutation was the 5T allele. One patient with CBAVD and a single Delta F508 CFTR mutation also had left renal agenesis. In conclusion, we strongly recommend that genetic counselling, chromosomal analysis and, in the case of CBAVD, screening for CFTR mutations should be offered to all couples with a diagnosis of male or idiopathic infertility.

PGM3 deficiency

Typically, both parents of an affected child carry one abnormal gene and are unaffected by the disease. When both parents have one abnormal copy of the PGM3 gene, each child has a 25 percent chance of being affected by the disease. Sometimes the two copies of the PGM3 gene that a child inherits have identical, or homozygous, mutations. This is common if the child’s parents are related to each other, explaining why many reported cases of PGM3 deficiency have involved consanguinity families. Many patients have different mutations on the two copies of PGM3, and their mutations are called compound heterozygous mutations. In either case, the patient is not able to produce functional PGM3 protein Diagnosis

Proband and parent assistance in identifying relatives for cystic fibrosis carrier testing.

To identify, contact, and offer free cystic fibrosis (CF) carrier education, testing, and genetic counseling to the first, second, and third degree relatives of individuals with CF, study personnel contacted probands or the parents of minor probands requesting assistance in identifying relatives. We requested family pedigrees, including names, addresses, and phone numbers and if necessary a saliva sample for determination of the specific CF mutations in the family. Two hundred three families of 220 probands being followed at a large CF clinic in the Southeastern United States were eligible for inclusion in the study. Of the 203 families 109 (53.7%) assisted by providing contact information on relatives and, when necessary, a saliva sample for mutation analysis. An additional 33 (16.4%) agreed to assist but did not provide either or both contact information or saliva samples. Sixty-one (30.1%) declined to provide assistance. Thirteen percent of the probands/parents wanted to talk with relatives before providing contact information. A logistic regression model predicting proband/parent assistance is provided. This study suggests that the active outreach method used here to identify at risk relatives to offer them CF carrier testing resulted in somewhat lower proband or parent assistance than reported by other similar approaches. The strengths and weaknesses of this approach, including comments by probands and parents on the method, are discussed.

Obligate carrier

In X-linked recessive disorders, only females can be the carriers of the recessive mutation, making them obligate carriers of this type of disease. Females acquire one X-chromosome from their father and one from their mother, and this means they can either be heterozygous for the mutated allele or homozygous. If heterozygous, she is a carrier of the mutated allele because the disease is recessive. If homozygous, she has the disease. An affected father with an X-linked recessive trait will always pass the trait on to the daughter. Therefore, all daughters of an affected male are obligate carriers. On the other hand, a carrier mother has a 50% chance of passing her mutated X-chromosome to the daughter. This makes all daughters of carrier mothers possible carriers but not necessarily obligate carriers. Males cannot be obligate or possible carriers of X-linked recessive traits because they only have one X-chromosome, and so are always phenotypically affected when receiving the mutated

Survey of CF mutations in the clinical laboratory.

BACKGROUND: Since it is impossible to sequence the complete CFTR gene routinely, clinical laboratories must rely on test systems that screen for a panel of the most frequent mutations causing disease in a high percentage of patients. Thus, in a cohort of 257 persons that were referred to our laboratory for analysis of CF gene mutations, reverse line probe assays for the most common CF mutations were performed. These techniques were evaluated as routine first-line analyses of the CFTR gene status. METHODS: DNA from whole blood specimens was extracted and subjected to PCR amplification of 9 exons and 6 introns of the CFTR gene. The resulting amplicons were hybridised to probes for CF mutations and polymorphisms, immobilised on membranes supplied by Roche Molecular Systems, Inc. and Innogenetics, Inc. Denaturing gradient gel electrophoresis and sequencing of suspicious fragments indicating mutations were done with CF exon and intron specific primers. RESULTS: Of the 257 persons tested over the last three years (referrals based on 1) clinical symptoms typical for/indicative of CF, 2) indication for in vitro fertilisation, and 3) gene status determination because of anticipated parenthood and partners or relatives affected by CF), the reverse line blots detected heterozygote or homozygote mutations in the CFTR gene in 68 persons (26%). Eighty-three percent of those affected were heterozygous (47 persons) or homozygous (10 persons) for the DeltaF508 allele. The only other CF-alleles that we found with these tests were the G542X allele (3 persons), the G551D allele (3 persons), the 3849+10kb C-T allele (2 persons) the R117H allele (2 persons) and the 621+1G-T allele (1 person).Of the fifteen IVS8-5T-polymorphisms detected in intron 8, seven (47%) were found in males referred to us from IVF clinics. These seven 5T-alleles were all coupled with a heterozygous DeltaF508 allele, they make up 35% of the males with fertility problems (20 men) referred to us. CONCLUSIONS: In summary, the frequency of CF chromosomes in the cohort examined with these tests was 26%, with the DeltaF508 allele affecting 83% of the CF chromosomes. It is a substantial improvement for routine CF diagnostics to have available a test system for 30 mutations plus the polypyrimidine length variants in intron 8. Our results show that this test system allows a routine first-line analyses of the CFTR gene status.

A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens.

To report a novel cystic fibrosis transmembrane conductance regulator (CFTR) gene missense mutation in a compound heterozygote with congenital bilateral absence of the vas deferens (CBAVD). Descriptive, controlled study. Tertiary academic hospital genetics laboratory and private in vitro fertilization (IVF) clinic. One 46-year-old man with CBAVD and no clinical cystic fibrosis (CF) phenotype as indicated by the advanced age at diagnosis, absence of chronic airways and gastrointestinal disease, and normal pancreatic function and sweat chloride concentration. Genomic blood DNA from the patient's parents was analyzed to perform family studies, and 109 fertile men, 32 patients with CBAVD, 15 children carriers of one CFTR mutation, and 5 patients with CF were used to rule out polymorphism. Clinical evaluation and treatment, genetical screenings. Clinical data, biochemical assays, spermiogram analysis, testicle biopsy, intracytoplasmic sperm injection (ICSI) outcome, and CFTR whole gene mutation screening and IVS8T polymorphism. The DNA analysis revealed a 7T/7T homozygote at IVS8-T, with a 4000C-->T change (P1290S) in exon 20 of the CFTR gene, which was inherited from the patient's father. It was associated with a 3272-26A-->G mutation in the other allele that was inherited from his mother. The novel P1290S missense CFTR mutation causes an amino acid change in a highly conserved region of the CFTR protein that controls channel opening. Pathogenicity is suggested by development of CBAVD in association with a mild CFTR mutation.

Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene.

Methylmalonic acidemia (MMA), which is an autosomal recessive metabolic disorder, is caused by mutations in methylmalonyl-CoA mutase (MUT) gene. As a result, the conversion of methylmalonyl-CoA to succinyl-CoA is impaired in this disorder, leading to a wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. Since identification of novel mutations in MUT gene can help discover the exact pathogenesis of MMA and also use these disease-causing mutations in prenatal diagnosis, this study was conducted to uncover the possible mutations in an Iranian couple with a deceased offspring clinically diagnosed as having organic acidemia. Moreover, to prevent the occurrence of the mutation in the next pregnancy, we took the advantage of pre-implantation genetic diagnosis (PGD), which resulted in a successful pregnancy. The affected individual was a 15-month-old boy who passed away due to aspiration pneumonia. The child presented at the age of 3 months with lethargy, protracted vomiting, hypotonia, and decreased level of consciousness. To find the mutated gene, Next Generation Sequencing (NGS) was performed as carrier testing for the parents and the results revealed a novel (private) heterozygous missense mutation in MUT gene (c.1055A > G, p.Q352R). After performing PGD on three blastomeres, one was identified as being homozygous wild-type that was followed by successful pregnancy. Our study identified a novel, deleterious, heterozygous missense mutation in MUT gene in a couple and helps to consider the genetic counselling and prenatal diagnosis more seriously for this family with clinical phenotypes of organic acidemia.

Mutations in CFTR gene and clinical correlation in Argentine patients with congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) is a form of male infertility in which mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been identified. Here we identify different mutations of CFTR and the poly-T variant of intron 8 (IVS8) in Argentine patients and analyze sweat test values and clinical characteristic related to Cystic Fibrosis (CF). For counseling purposes the two most frequent mutations in Argentine CF population: deltaF508 and G542X were screened in wives. In all cases, it was possible to reduce the risk of CF/CBAVD descendants in these couples because none of the mutation were found in the 36 samples. Eight patients (23%) showed abnormal chloride values (> 60 mmol/l). A second group of 6 patients (18%) had borderline values of sweat chloride (40-59 mmol/l). We defined another group with 6 patients (18%), with normal sweat chloride levels (30-39 mmo/l) and a fourth group of 14 (41%) patients with sweat chloride below 30 mmol/l. deltaF508, the most frequent CF mutation in the Argentine population, was found on 15 of the 72 chromosomes (21%), R117H mutation was detected on 2 of 62 chromosomes (3%). Only one R347P allele was found on 28 chromosomes analyzed (2%). On a sample of 27 patients, IVS8 analysis showed a frequency of 6/56 chromosomes (11%) of 5T allele. Even though these findings present an improvement in the detection of mutations related to clinical correlations in Argentine CBAVD population, the search for other common and uncommon mutations should be continued.


We are presented with a 68-year-old female patient. At that age the crystalline lens, although it does not normally have a cataract that needs surgery, it usually has increased in thickness. This implies that it projects the iris forward and reduces the depth of the anterior chamber. In an eye with a normal anterior chamber depth this is usually not a problem. But farsighted people already have a narrow anterior chamber. This is the usual combination we find in primary angular closure: farsightedness and age over 50-60 years. Younger hyperopes usually do not have this problem yet. And neither do older people who are emmetropic, myopic or have had cataract surgery. With this narrow angle, what triggers angular closure is mydriasis. That is, when you are in the penumbra, the pupil dilates and the iris thickens in the peripheral part, where it is already very close to the corneal endothelium in the case of a narrow chamber. Mydriasis then triggers angular closure, which is accompanied by ocular pain that may radiate backwards (headache). And increased intraocular pressure produces corneal edema that causes blurred vision. Therefore, option 1 is correct. Migraine does not have to be related to penumbra, and ocular pain and blurred vision is not particularly typical. Actinic keratitis is caused by exposure to ultraviolet radiation (such as solar radiation), and is not related to hyperopia or to being in penumbra. In addition, the history of exposure is usually clear. And finally, dry eye does not produce these symptoms either: it is more a question of burning, foreign body sensation, heaviness, etc. And it is also unrelated to the other elements: penumbra, hyperopia, etc. As a minor detail, I would have worded the question a little better. It is understood that we are asked which pathology is the most probable in relation to the symptoms and the anamnesis. But as it is worded, we are asked about which of the pathologies she is most likely to present, just like that. Actually, a 68-year-old woman is very likely to have dry eye, even if it does not cause the symptoms for which she is presenting.

We are presented with a 68-year-old female patient. At that age the crystalline lens, although it does not normally have a cataract that needs surgery, it usually has increased in thickness. This implies that it projects the iris forward and reduces the depth of the anterior chamber. In an eye with a normal anterior chamber depth this is usually not a problem. But farsighted people already have a narrow anterior chamber. This is the usual combination we find in primary angular closure: farsightedness and age over 50-60 years. Younger hyperopes usually do not have this problem yet. And neither do older people who are emmetropic, myopic or have had cataract surgery. With this narrow angle, what triggers angular closure is mydriasis. That is, when you are in the penumbra, the pupil dilates and the iris thickens in the peripheral part, where it is already very close to the corneal endothelium in the case of a narrow chamber. Mydriasis then triggers angular closure, which is accompanied by ocular pain that may radiate backwards (headache). And increased intraocular pressure produces corneal edema that causes blurred vision. Therefore, [HIDDEN]. Migraine does not have to be related to penumbra, and ocular pain and blurred vision is not particularly typical. Actinic keratitis is caused by exposure to ultraviolet radiation (such as solar radiation), and is not related to hyperopia or to being in penumbra. In addition, the history of exposure is usually clear. And finally, dry eye does not produce these symptoms either: it is more a question of burning, foreign body sensation, heaviness, etc. And it is also unrelated to the other elements: penumbra, hyperopia, etc. As a minor detail, I would have worded the question a little better. It is understood that we are asked which pathology is the most probable in relation to the symptoms and the anamnesis. But as it is worded, we are asked about which of the pathologies she is most likely to present, just like that. Actually, a 68-year-old woman is very likely to have dry eye, even if it does not cause the symptoms for which she is presenting.

A 68-year-old woman who uses +4.00 diopter glasses for distance vision in both eyes. She consults because she has been having eye pain with headache and blurred vision at night when she is watching television in dim light for a few weeks. Which of the following pathologies is she most likely to have?

First_Aid_Step2

Dx: Diagnosis is based on clinical history and examination. Those that resolve may mimic a migraine headache with blurred vision; the distinction is that the headaches and blurred vision are more likely to be triggered by darkness (due to pupillary dilation) rather than by bright lights (migraine). Tx: This is a medical emergency that can cause blindness. Treatment to ↓ IOP may include eyedrops (timolol, pilocarpine, apraclonidine) or systemic medications (oral or IV acetazolamide, IV mannitol). Laser peripheral iridotomy, which creates a hole in the peripheral iris, is curative and may be performed prophylactically. generally occurs bilaterally, ■Flow of aqueous humor through the trabecular meshwork is limited, in- creasing IOP. A diseased trabecular meshwork obstructs proper drainage of the eye, leading to a gradual ↑ in pressure and progressive vision loss. occurs unilaterally.

Migraine

Differential diagnosis Other conditions that can cause similar symptoms to a migraine headache include temporal arteritis, cluster headaches, acute glaucoma, meningitis and subarachnoid hemorrhage. Temporal arteritis typically occurs in people over 50 years old and presents with tenderness over the temple, cluster headache presents with one-sided nose stuffiness, tears and severe pain around the orbits, acute glaucoma is associated with vision problems, meningitis with fevers, and subarachnoid hemorrhage with a very fast onset. Tension headaches typically occur on both sides, are not pounding, and are less disabling. Those with stable headaches that meet criteria for migraines should not receive neuroimaging to look for other intracranial disease. This requires that other concerning findings such as papilledema (swelling of the optic disc) are not present. People with migraines are not at an increased risk of having another cause for severe headaches. Prevention

Spontaneous filtering bleb with subsequent secondary glaucoma June consultation #1.

A 32-year-old previously healthy woman was referred for evaluation and management of newly diagnosed hypotony in the right eye. Her ocular history was significant only for moderate myopia and an idiopathic Horner syndrome in the left eye diagnosed at age 13. The patient endorsed a history of fluctuating and decreasing vision in the right eye over the past 6 months. She denied any ocular pain, previous ocular surgery, or recent trauma. The patient was otherwise healthy and denied any previous autoimmune disease or systemic infection. She wore soft, daily disposable contact lenses and reported no abnormalities on previous routine eye examinations. At presentation, the patient's uncorrected distance visual acuity was 20/25 in the right eye and 20/200 in the left. Lensometry revealed a previous refraction of -3.00 + 0.50× 150 in the right eye and -4.00 + 1.75× 174 in the left. Intraocular pressures (IOPs) were 4 mm Hg and 15 mm Hg by applanation, and central corneal thicknesses were 573 μm and 564 μm in the right and left eyes, respectively. Slitlamp examination revealed an area of scleral thinning near the limbus in the right eye from 5 to 7 o'clock with mild overlying chemosis (Figure 1JOURNAL/jcrs/04.03/02158034-202107000-00023/figure1/v/2021-06-26T110826Z/r/image-tiff). Gonioscopy showed an open angle with mild trabecular meshwork pigmentation in both eyes without any cyclodialysis clefts, peripheral anterior synechiae (PAS), or other abnormalities. Dilated fundus examination was significant for mild optic nerve edema and chorioretinal folds in the right eye. Optical coherence tomography (OCT) of the optic nerve confirmed mild disc edema (Figure 2JOURNAL/jcrs/04.03/02158034-202107000-00023/figure2/v/2021-06-26T110826Z/r/image-tiff) and OCT of the macula confirmed mild chorioretinal folds. Anterior segment OCT (AS-OCT) and ultrasound biomicroscopy failed to show any other abnormalities. The patient was initially observed without treatment and presented urgently approximately 1 month later with decreased vision and ocular discomfort. Repeat examination revealed an IOP of 31 mm Hg and a focal area of PAS to the previous area of scleral thinning (Figure 3JOURNAL/jcrs/04.03/02158034-202107000-00023/figure3/v/2021-06-26T110826Z/r/image-tiff). In one respect, the newly elevated IOP was considered transiently therapeutic to help reverse the hyperopic shift, disc edema, and hypotony-related maculopathy. However, the situation quickly became more worrisome when shortly thereafter the IOP elevated to 55 mm Hg at subsequent follow-up, and multiple IOP-lowering medications were initiated. Over numerous additional visits, the patient's IOPs ranged from 30 to 39 mm Hg in the right eye despite rapidly advancing to maximally tolerated medical therapy including acetazolamide. She was noted to have a new relative afferent pupillary defect of the right eye, and Humphrey visual fields showed early arcuate defects (Figure 4JOURNAL/jcrs/04.03/02158034-202107000-00023/figure4/v/2021-06-26T110826Z/r/image-tiff). What would be your approach to managing this healthy, young, myopic woman who presented with hypotony due to a spontaneous, perilimbal filtration bleb that later occluded with PAS, resulting in intractably elevated IOP and field loss? What is the differential diagnosis? Would you perform a systemic workup for her initial scleral thinning, and if so, what would you check? Would you intervene for her elevated IOP in the right eye? If so, what would be your surgical approach?

Macular folds: an unusual association in topiramate toxicity.

We report two uncommon cases of acute onset myopia with macular folds following use of topiramate. A 25-year-old woman, with no prior history of glasses, taking topiramate for recurrent headaches, presented with decreased vision. On examination, she was found to have a refractive error of -5.00 DS in both eyes and intraocular pressure of 10 mmHg and 6 mmHg in the right and left eyes, respectively. She had closed angles on gonioscopy, ciliary effusion on ultrasonic biomicroscopy with inner limiting membrane folds in the macula in both eyes. She was on anti-glaucoma medication when she presented to us. A 20-year-old woman presented with acute headache and decreased vision following use of topiramate for treatment of migraine. On examination, her intraocular pressure was 25 mmHg in both eyes with closed angles on gonioscopy, a refractive error of -4.50 DS and prominent macular folds with no fluid in both eyes. There was complete resolution of macular folds and angle-closure attack after discontinuation of topiramate and conservative treatment with topical steroids and cycloplegics in both eyes. Topiramate toxicity may present with macular folds associated with angle-closure glaucoma. Folds in the inner limiting membrane might give a clue to choroidal effusion as the cause for this presentation. The symptoms resolved on the discontinuation of topiramate.

Dry Your Eyes (TV series)

Stage show In the spring of 2007 Dry Your Eyes it's Give My Head Peace played sell-out shows at two venues in Northern Ireland; the Millennium Forum in Derry from 19 to 24 March and at Belfast's Grand Opera House from 26 March – 7 April. The show featured new material from Dry Your Eyes and Give My Head Peace and Tim McGarry also performed stand-up comedy. It was very well received. The next show in 2008, Give My Head Peace: Back from the Grave, also featured stand-up comedy and appearances by Dry Your Eyes characters Derek and the McDowell Brothers alongside the regular Give My Head Peace cast.

Aripiprazole-Induced Acute Transient Bilateral Myopia: A Case Report.

Aripiprazole is an atypical, antipsychotic drug used for the treatment of schizophrenia, depression, bipolar disorder, and obsessive-compulsive disorder in adults. There are a few reports in the literature of ocular side effects of aripiprazole, such as transient myopia, diplopia, and acute angle closure. This report describes the case of a 34-year-old female patient who was referred to the clinic with painless blurred vision in both eyes. She had been diagnosed with major depression and had been using aripiprazole for a month. She experienced blurred vision after the first week of drug therapy. The uncorrected visual acuity (UCVA) was 4/10 in both eyes using a standard Snellen chart. She had a refractive error of -2.00 diopters and the best corrected visual acuity was 10/10 in both eyes. The ocular examination results were normal other than the refractive error. The patient was diagnosed with aripiprazole-induced, acute transient myopia. The UCVA was 10/10 in both eyes at the 2-week follow-up following termination of the aripiprazole therapy. It is important to be prepared to recognize aripiprazole-induced, acute transient myopia in patients complaining about blurred vision.

Importance of eye disease in headache.

Patients who consult primary health care providers with headache accompanied by ocular symptoms should be referred to an ophthalmic casualty department.

Bilateral acute angle-closure glaucoma following treatment with topiramate for headache.

This case report adds supportive evidence to the development of acute angle-closure glaucoma (AACG), a rare but serious adverse effect following the use of topiramate (TPM) for a severe headache. A 25-year-old female reported with severe headache, suspected to be migraine, and was started on TPM 25 mg/day on the first day. However, she presented at the emergency clinic of a hospital with sudden blurring of vision and colored halos 5 days after stopping the drug, i.e., day 8. She was subjected to ophthalmic examination and was diagnosed with AACG. The intraocular pressure (IOP) was found to be elevated and she was hence started on acetazolamide 500 mg instantly, maintained on tablet acetazolamide 250 mg four times a day (QID), pilocarpine 2% eye drops QID, travoprost 0.004% once a day (OD), and dorzolamide 2% eye drops three times a day (TID). After a week's treatment, there was rapid improvement with return of IOP to normal. TPM-induced AACG is a rare serious adverse event leading to blindness but is preventable, when diagnosed early and by instituting appropriate treatment.

Ophthalmodynia periodica

Ophthalmodynia periodica is also known as "ice-pick headache", is a primary headache disorder, so it is not caused by any other conditions. Signs and symptoms Stabbing sensations, usually in one area of the head Pain may move to different areas of the head Pain lasts for a few seconds ("usually 5–30") Pain appears out of nowhere Pain is completely gone after each occurrence Each occurrence happens at varied frequencies Cause Ophthalmodynia periodica does not have a confirmed cause, being a primary headache, but can be identified with other primary conditions. "As many as 40% of all individuals with ice pick headaches have also been diagnosed as suffering with some form of migraine headache." Diagnosis The following diagnostic criteria are given for ophthalmodynia periodica:

Topiramate-associated acute, bilateral, angle-closure glaucoma: case report.

This paper describes a topiramate induced acute bilateral angle-closure glaucoma. This rare adverse effect is an idiosyncratic reaction characterized by uveal effusion and lens forward displacement, leading to increased intraocular pressure and vision loss. We describe a 55 year-old white woman with migraine, spasmodic torticollis and essential tremor, who developed bilateral acute angle-closure glaucoma, one week after starting topiramate 25 mg/day. She was seen at the Ophthalmology Emergency Department of the Fundação João Penido Burnier (Campinas, SP, Brazil) with a 4 hours history of blurry vision, ocular pain and bright flashes vision. Slit lamp examination revealed moderate conjunctival injection and corneal edema, and shallow anterior chambers. Intraocular pressure was 48 mmHg in both eyes. Fundoscopic examination findings were normal. She was treated with timolol, brimonidine, dorzolamide, pilocarpine, prednisone acetate eye drops and acetazolamide. One hour after those measures, as the intraocular pressure was 30 mmHg, she received a manitol intravenous injection and the intraocular pressure normalized. After 24 hours an iridotomy with Yag laser was performed. Topiramate was discontinued and she was totally recovered after one week.

[Ocular findings in patients older than 99 years].

To determine vision conditions and ocular findings in patients older than 99 years. Patients were recruited by media advertisement and examined at the Vision Institute of UNIFESP. The following examinations were performed: visual acuity, ectoscopy, refraction, biomicroscopy, tear film break-up time, Schirmer basal test, tonometry, direct and indirect ophthalmoscopy. Complementary examinations such as optical coherence tomography were performed when indicated. Thirty patients older than 99 years were identified. Mean age of 101.5+/-1.8, 25 females and 5 males. Most common systemic disease, according to history, was arterial hypertension. In 11 patients (55%), the best corrected far visual acuity was 20/100 or better. The best corrected near visual acuity was J4 or better also in 55% (11 patients) and 63.0% (7 patients) of these were the ones that had not been submitted to cataract surgery. The most frequent visual complaint was low vision for reading (55%) and other 8 patients (40%) reported no disturbance (satisfied with their vision). Lens opacity was present in 9 patients (60%) and 8 patients (40%) had previous cataract surgery (5 aphakic eyes, 9 pseudophakic eyes). Cataract was identified as important for impairment of vision in 5 patients but only 2 of them wanted to be submitted to surgery. The main cause of visual impairment was age-related macular degeneration, present in all patients, 95% with no exudative form. Vision improved with new refractive prescription in 4 patients. Once we understand the needs we can plan specific diagnostic and treatment strategies. This sample showed that most were female (83.3%), with good general health (35%), most with systemic arterial hypertension (40%), complaining of low vision for reading (55%) because of age-related macular degeneration (100%, 95% dry form). Only 40% had been previously submitted to cataract surgery. Most of the patients with cataract said to be satisfied with their vision; of the 5 patients that could be operated only 2 decided to do it. Low vision for reading, AMD and cataract were the main findings.

[Angle-closure glaucoma: important points in the diagnosis and follow-up].

A 74-year-old woman visited her local physician complaining of fever, cough, headache, hyperemic left conjunctiva, and blurred vision. She was diagnosed as having common cold and medicated for it, and later, she visited our department. She had a shallow left anterior chamber with moderately dilated pupil. Gonioscopic examination of the left eye revealed a narrow angle corresponding to grade 1 by Shaffer grading system. Left intraocular pressure was 16 mmHg. She was diagnosed to have had a spontaneous recovery from a subacute attack of angle-closure glaucoma. Laser iridectomy was performed and she was put on a regular ophthalmological follow-up. Three years later, she experienced an attack of left angle-closure glaucoma secondary to lens intumescence. She was treated by phacoemulsification and aspitaion which resulted in the eventual cure.

Dry Your Eyes (TV series)

Nameless characters While each of these characters had names in the script, none of them are mentioned in the show itself.

Bilateral posterior crystalline lens dislocations in an otherwise healthy child.

<bIntroduction:</b Ectopia lentis is defined as a crystalline lens displacement, either partially or completely, due to zonular abnormalities. It can be a result of trauma, hereditary ocular disease, or part of systemic diseases, like Marfan syndrome and homocystinuria. <bCase description:</b We report a case of a medically free 16-year-old girl, who was referred to our hospital complaining of poor vision and a squint in both eyes since childhood. Her history included a traffic accident when she was one-year-old. She was previously diagnosed with alternating esotropia, which was treated with glasses, alternating patching, and bilateral Botox injections. On examination, she had a visual acuity of 6/7.5 with correction in the right eye and 6/6 with correction in the left eye. She had an esotropia of 60 prism diopters, which was partially corrected to 40 prism diopters for near and distance vision. Fundus examination showed myopic changes in each eye and dislocated lenses in the posterior pole at 6 o'clock. Our case was stable, so we used conservative management with contact lenses. <bConclusion:</b Bilateral posterior lens dislocation is very rare. A proper examination is important and early diagnosis can prevent serious complications, such as retinal detachment or pupillary block glaucoma.

Daylight in Your Eyes

in the United Kingdom and the United States, respectively, "Daylight in Your Eyes" also saw minor commercial success in both countries with peak positions of number 88 on the UK Singles Chart and a single entry at number 36 on the Billboard Hot Singles Sales chart.

Neurotrophic keratitis in autoimmune polyglandular syndrome type 1: a case report.

Autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive disease. In patients with APS-1, the most frequently reported ocular manifestations are keratoconjunctivitis with dry eye and retinal degeneration. However, to our knowledge, no research studies have reported the relationship between APS-1 and neurotrophic keratitis (NK). Possible explanations such as limbus cell deficiency being the primary cause of APS-1 keratopathy are not applicable to our unusual case of the patient with APS-1 presenting as ocular surface disease with NK. Our case findings suggest a new explanation for the observed corneal pathology and a potential treatment for these patients. A 27-year-old woman was referred to our hospital because of intermittent blurred vision and recalcitrant ocular surface problems in both eyes for many years. She has a history of autoimmune polyglandular syndrome type 1 (APS-1), which includes hypothyroidism, hypoparathyroidism, hypoadrenalism, and hypogonadotropic hypogonadism. In vivo confocal microscopy clearly demonstrated significant degeneration of the sub-basal nerve plexus and stromal nerve bundles in her corneas bilaterally. She was diagnosed with severe NK and ocular surface disease caused by dry eye. Treatment included the application of therapeutic soft contact lenses and punctual occlusion; however, both treatments had a limited effect. Patients with APS-1 may have ocular surface disease and severe damage to corneal nerves. Regular follow-up and treatment focusing on the regeneration of corneal nerves is particularly important in these patients.

Ocular ischemic syndrome; A case report.

Ocular ischemic syndrome is not a common condition so most of these cases are often misdiagnosed or treated as a different entity. Therefore, it is very important for the ophthalmologists to have this condition in mind as a differential so that the patients can be diagnosed and treated as early as possible. A 42 years female presented with painless, progressive diminution of vision in right eye over the period of 1 month. She doesn't give any history of redness of eyes, fever or trauma. There is no history of diabetes mellitus or hypertension as well. On examination, vision in right and left eyes was 1.78 and 0.30 Log Mar Units respectively. On anterior segment examination, revascularization of iris (1o 4 'o'clock hrs) in right eye was noted. On dilated fund us copy, revascularization of disc (1/3rd) was present in right eye. Cotton wool spots blot hemorrhages and micro aneurysms were also noted in right eye. Likewise, attenuation of arteries were noted on both sides. Fund us fluorescent angiography revealed delayed artery covetous and venous phase. Carotid Doppler was done which showed complete occlusion of right common carotid and bilateral internal carotid artery. These findings lead to the diagnosis as ocular ischemic syndrome so she was then referred to the cardiologist who further confirmed that no active intervention was required at present. The patient was planned for right eye pan retinal photocoagulation (PRP) and was completed in 2 sittings and was asked to follow up regularly. Early diagnosis and management is very important for uncommon conditions such as ocular ischemic syndrome to prevent further complications.

The Use of Topiramate for Weight Loss Causing Acute Glaucoma: A Case Report and Literature Review.

Topiramate is a sulfa-containing drug which is able to disrupt the ocular blood barrier. Recently it has gained more popularity, being used in many clinical conditions. Nowadays, the cases of glaucoma induced by topiramate have increased due to the use of this drug to induce weight loss. We here described a 29-year-old female presented with a one-day history of blurred vision in both eyes and headache. She was using a weight loss formula containing topiramate 100 milligrams. Ophthalmologic exam revealed an important myopic shift of -7.00 spherical diopters at presentation with intraocular pressure (IOP) of 32 mmHg and a shallow anterior chamber in both eyes. After discontinuous of topiramate and use of cycloplegic eyedrops, myopic shift improved and IOP controlled after two days. The anterior chamber was significantly deeper in both eyes after two weeks. It is theorized that topiramate can provoke a ciliochoroidal effusion and, therefore, can cause an anterior displacement of lens-iris diaphragm with a secondary angular closure. The treatment must include cycloplegic and discontinuation of the drug. Sulfa-containing drugs lead to an indirect mechanism of angle closure, frequently bilateral and, as mentioned above, with a different treatment approach. If unrecognized and untreated, it can provoke high morbidity with possibility of bilateral permanent visual loss.

Acanthamoeba keratitis due to genotype T11 in a rigid gas permeable contact lens wearer in Spain.

A case of a 59-year-old Spanish patient who presented with severe ocular pain, blurred vision, eyelid swelling and foreign body sensation in the right eye is reported. She was a regular gas permeable contact lens [corrected] wearer who initially claimed to maintain standard lens care. After exploration, conjunctival injection, dendritiform corneal ulcers and stromal edema were observed. She was initially treated for a possible viral keratitis due to herpes simplex virus using 3% topical acyclovir and 0.1% dexamethasone eye drops 5 times a day. The patient did not respond to this treatment and six weeks later, corneal scrapings were positive for Acanthamoeba genotype T11. She was then treated with chlorhexidine 0.02%, propamidine 0.1% and 1% cycloplegic eye drops hourly which resulted in a significant improvement. After a month, ocular pain decreased and the clinical signs of keratitis ameliorated observed as a diminution of the size of the ulcer and also in the extension and opacity of the corneal infiltrates. The patient has been following this treatment for 3 months and it is possible that she will have to carry on with it for a whole year. To the best of our knowledge, this is the first case of severe keratitis due to Acanthamoeba genotype T11 in Spain .

The Gentlemen (2019 film)

Unknown to Pearson, Dry Eye is in league with Berger, who had wanted Pearson's business disrupted to reduce the price. Dry Eye has taken Lord George's place and still hopes to take Pearson's empire for himself. Dry Eye tries to kidnap Rosalind, who kills Dry Eye's men before she runs out of bullets in her two-shot derringer. Raymond kills an assassin sent to kill Pearson; the two rush to Rosalind and Pearson fatally shoots Dry Eye as he is about to rape her. Fletcher ends his story and Raymond orders him to leave his house.

Fish allergy causing angioedema and secondary angle-closure glaucoma.

A 56-year-old woman with a history of primary angle-closure glaucoma presented with acute generalised swelling, and facial angioedema following a fish meal. She complained of nausea, vomiting, headache, pain in both eyes and acute loss of vision. Her visual acuity was reduced and intraocular pressures (IOP) were elevated. Gonioscopy revealed complete angle closure in the left eye and complete to partial closure in the right eye. Through existing peripheral iridotomies the anterior capsules were seen pressed up against the iris of both eyes. A diagnosis of angle-closure glaucoma was made, medications were started to reduce the elevated intraocular pressure and systemic antihistamine to counter the allergic reaction. She was hospitalised for further management. A follow-up at 2 years revealed her visual acuities and IOP had remained normal.

InternalMed_Harrison

Vitreous Degeneration This occurs in all individuals with advancing age, leading to visual symptoms. Opacities develop in the vitreous, casting annoying shadows on the retina. As the eye moves, these distracting “floaters” move synchronously, with a slight lag caused by inertia of the vitreous gel. Vitreous traction on the retina causes mechanical stimulation, resulting in perception of flashing lights. This photopsia is brief and is confined to one eye, in contrast to the bilateral, prolonged scintillations of cortical migraine. Contraction of the vitreous can result in sudden separation from the retina, heralded by an alarming shower of floaters and photopsia. This process, known as vitreous detachment, is a common involutional event in the elderly. It is not harmful unless it damages the retina. A careful examination of the dilated fundus is important in any patient complaining of floaters or photopsia to search for peripheral tears or holes. If such a lesion is found, laser

Adie's tonic pupil-induced angle-closure glaucoma.

A 52-year-old woman was diagnosed as having Adie's tonic pupil in her right eye. She reported few episodes of blurring of vision in her right eye in the recent few months. On one of the routine follow-up visits, right intraocular pressure (IOP) was 70 mm Hg and on gonioscopy the angle was closed 360 degrees. Medical treatment resulted in IOP reduction and laser iridotomy was then performed. This is, to our knowledge, the first description of intermittent angle-closure glaucoma attacks induced by a tonic pupil. The possibility of angle-closure glaucoma should be considered in patients with a tonic pupil, especially with symptoms of blurred vision or ocular pain.

Dry eyes. Eye series. 3.

During her regular check-up a 68 year old woman patient mentions, as an aside, that the recent hot weather has left her eyes with a 'dry, gritty feeling'. The feeling is more noticeable toward the end of the day and on further questioning has gradually become more prominent over the past few years.

Unusual case of angle closure glaucoma in a patient with neurofibromatosis type 1.

We report the case of a 29-year-old female patient who presented with an acute onset of anisocoria, blurred vision, nausea and severe left-sided headache. There was no history of trauma, drug abuse, or instillation of topical mydriatic compounds. The ocular history was negative for similar events. On presentation, her visual acuity was 0.2 in the left and 1.0 in the right eye with a +2.5 dpt sph. correction. Slit-lamp examination demonstrated a shallow anterior chamber as well as the presence of iris nodules in both eyes. These nodules were identified as Lisch nodules as the patient referred to the previous diagnosis as being neurofibromatosis type 1. A third nerve palsy was considered, but a brain MRI showed normal results. Her ocular motility was normal, but the left pupil was mydriatic and poorly reacting to light, with an associated raised intraocular pressure (IOP) of 38 mm Hg. An examination of the fellow eye was normal, with the IOP measuring 18 mm Hg. Gonioscopy of the right eye showed a narrow angle. On further anamnestic investigation, the patient revealed that the pain and the blurred vision begun in the morning while she was helping her mother in the garden. Finally, after showing the patient a picture of Datura flowers, which she recognized immediately, we made the unusual diagnosis of angle closure glaucoma by Datura, a well-known toxic plant with mydriatic properties. The patient was successfully treated with systemic acetazolamide and topical pilocarpine.

Third Eye Blind discography

After signing with Elektra Records, Third Eye Blind released their self-titled debut album in 1997. Helped by the singles "Semi-Charmed Life", "Graduate", "How's It Going to Be", "Losing a Whole Year", and "Jumper", the album peaked at number 25 on the Billboard 200 chart, sold six million copies, and went six times platinum in the United States. "Semi-Charmed Life" peaked at number four on the Billboard Hot 100. Their second album, 1999's Blue, included "Anything", "Never Let You Go", "10 Days Late", and "Deep Inside of You". Blue peaked at number 40 and went platinum in the US.

Anterior segment reconstruction due to cosmetic iris implants placed in the anterior chamber.

A 27-year-old woman had BrightOcular iris implants placed for cosmetic purposes that changed eye color from brown to blue bilaterally. Of note, BrightOcular implants are not approved by the U.S. Food and Drug Administration (FDA) for use in the United States and have been associated with severe ocular complications. In keeping with their design, they were placed in the anterior chamber (AC) in both eyes of this patient; surgery was performed outside the United States. As has been described previously and tragically in other cases, she developed chronic inflammation, intolerable glare, angle-closure glaucoma, corneal edema, and cataracts in both eyes. For medically unmanageable elevated intraocular pressure (IOP), she underwent diode laser cyclophotocoagulation (CPC) in both eyes, and eventually, an Ahmed tube shunt (New World Medical, Inc.) was placed in the right eye. Although she was advised and urged to have the iris implants removed, despite her ocular issues, she refused removal until intolerable glare and reduced vision ensued. Ultimately, both iris implants were extracted 5 years after implantation by a U.S. surgeon; the procedures resulted in corneal decompensation and progressive cataract development. Subsequent penetrating keratoplasty (PKP) was performed for the right eye, but it failed because of contact with the glaucoma tube shunt. She sought additional consultation and presented with the following findings: corrected distance visual acuity was 20/400 in the right eye and 20/40 in the left eye, IOP of 18 mm Hg in the right eye and 16 mm Hg in the left eye, pupils were nonreactive and fixed, and extraocular muscles and central visual field were normal. Pachymetry was 868 μm in the right eye and 653 μm in the left eye. Anterior segment examination in the right eye revealed a failed corneal graft with 3+ edema, peripheral anterior synechiae (PAS) for 360 degrees, shallow AC, Ahmed tube shunt at the 11 o'clock position and remnant iris adherent to the graft-host junction for 270 degrees, 3+ posterior subcapsular cataract, and 2+ cortical cataract (Figure 1JOURNAL/jcrs/04.03/02158034-202208000-00024/figure1/v/2022-08-01T210317Z/r/image-tiff). The sclera revealed multiple circular and circumferential atrophic blue spots consistent with high-energy transscleral CPC (Figure 2JOURNAL/jcrs/04.03/02158034-202208000-00024/figure2/v/2022-08-01T210317Z/r/image-tiff). In the left eye, she had remnant fixed dilated iris for 270 degrees, missing iris superiorly for 3 clock hours, an adequate AC, and 2+ cortical cataract (Figure 3JOURNAL/jcrs/04.03/02158034-202208000-00024/figure3/v/2022-08-01T210317Z/r/image-tiff). Posterior segment examination revealed a 0.5 cup-to-disc ratio in both eyes with normal vessels, macula, vitreous, and retinal periphery, bilaterally. Given this constellation of findings, how would you proceed?

List of Through the Dragon's Eye episodes

light shoots out of his hand and melts the object he is pointing at. He threatens to melt Morris as well, but Jenny decides it would be safer to help him after all. Doris tries to contact Boris as discreetly as possible, but Charn sees her at the last minute, and melts her.Clues in the Snow was aired on 24 October 1989

[A 56-year-old woman with adult-onset ophthalmoplegic migraine presenting with recurrent bilateral abducens nerve palsy].

A 56-year-old woman had been experiencing episodic left eye pain followed within 3 days by double vision and adduction of the left eye since the age of 30. The episodes occurred once per month, and her symptoms spontaneously resolved within 3 days. The patient was diagnosed with ophthalmoplegic migraine (OM) with left abducens nerve palsy at the age of 53 years. In May 2011, she developed bilateral retro-orbital pain followed by double vision and limitation of abduction of the right eye. She recalled having a cold and high fever 10 days before the onset of the headache. MRI showed no thickening or enhancement of the right abducens nerve. Constructive interference in steady-state (CISS) MRI showed neurovascular contact between the right abducens nerve and anterior inferior cerebellar artery. Right abducens nerve palsy accompanied by OM was diagnosed after other diseases that can cause ophthalmoplegia were excluded. The patient's eye symptoms gradually improved following steroid treatment. There have been a few similar case reports of adult patients with OM showing left and right abducens nerve palsy at different time points. In this case report, we discuss the possible mechanisms related to OM.

One-Eye, Two-Eyes, and Three-Eyes

Little table, away and the table would vanish. The wise woman then left and Little Two Eyes spoke the words the woman had told her would summon the table, and to her surprise there it stood. Little Two Eyes ate until she was full and said the words the woman told her would make the table disappear, and immediately it was all gone. Little Two Eyes returned home in the evening and found the plate of leftovers her sisters had left for her, but she did not touch it.

Anterior segment optical coherence tomography documentation of a case of topiramate induced acute angle closure.

We present a case report of a 31-year-old female patient who presented to us with a 1 day history of acute bilateral eye pain, blurred vision and headache. She was found to have a myopic shift, raised intraocular pressure (IOP) and shallow anterior chambers in both eyes. She had been commenced on oral topiramate 1 week previously. A number of investigations, including anterior segment optical coherence tomography (AS-OCT) were done and a diagnosis of topiramate induced bilateral acute angle closure (TiAAC) was made. Topiramate was discontinued and she was managed with topical and oral antiglaucoma medications, topical steroids and cyclopegics. Her symptoms subsided dramatically at the next follow-up. The AS-OCT documentation revealed lucidly the improvement in her anterior chamber depth and anterior chamber angle parameters. Her IOP decreased, her myopic shift showed reversal and her AS-OCT findings revealed gross improvement in all the parameters angle opening distance, trabecular iris space area and scleral spur angle. This case report clearly shows with AS OCT documentation the changes which occur in the anterior segment in a case of TiAAC.

"My eyes are turned outside".

A 78-year-old white woman noted progressively worsening headache, fluctuating decreased vision, dizziness, and binocular horizontal and vertical diplopia of two months duration. She had a 40 prism diopter exotropia and bilateral ophthalmoplegia. An initial temporal artery biopsy (TAB) was negative for findings of giant cell arteritis (GCA). Empiric prednisone was continued, and a second TAB was positive for GCA. In time there was complete resolution of the ophthalmoplegia.