Spinal muscular atrophy is a genetic disorder characterized by progressive muscular weakness.
The different types of spinal muscular atrophy may present differently but clinical symptomatology may be similar to some extent.
The following system-wise presentation is commonly in seen in SMAs:
General Appearance: Infant patients may initially present to be weak, floppy and flaccid.
Integumentary system: SMA type 1 babies may appear cyanotic upon birth.
Head and Neck: Sucking and swallowing ability is impaired.
Chest and heart: Respiratory difficulty may be presented with a hypotonic diaphragm muscle.
Abdomen: Hypotonic abdominal muscles may be observed in supple babies.
Extremities: Occasional tremors of fingers and muscular fasciculation may be observed in chronic infantile forms of SMA. Pseudohyperthrophy of gastrocnemius muscle (calf muscle) may be seen in SMA II.
Neurologic: Developmental and motor function delay are evident in SMA type 2. Late stage SMA may present with poor deep tendon reflexes.
Children can walk independently but may have difficulty walking or running, rising from a chair, or climbing stairs. Other complications may include curvature of the spine, contractures, and respiratory infections. [ninds.nih.gov]
While children with type III usually are able to walk, most have some difficulty walking. Some may eventually need to use a wheelchair. Symptoms usually appear around 18 months of age or in early childhood. [childrenshospital.org]
These children show signs of clumsiness, difficulty walking, mild muscle weakness, and may be developmentally delayed. These children live long into their adult years. [chw.org]
Developmental Delay
Developmental delays can be early signs of a serious medical condition. Always trust your instincts. If something about your child's development doesn't feel quite right, don't delay. Early diagnosis is key… it's a SMArt Move. [curesma.org]
These symptoms include: Developmental delays Inability to support the head Inability to sit up without assistance Breathing and swallowing difficulties which may lead to choking Spinal muscular atrophy Type 2 is less severe than type I and begins to develop [cedars-sinai.edu]
Children affected by spinal muscular atrophy (SMA) often have developmental delays. [babysfirsttest.org]
Unable to Stand
Children can sit without support but are unable to stand or walk unaided. Children also may have respiratory difficulties. [ninds.nih.gov]
Bone strength decreases as patients become unable to stand, and they are at risk for bone fractures (breaks). Also, scoliosis (spinal curvature) nearly always develops as these children grow. Life span may extend beyond the school years. [nationwidechildrens.org]
Recurrent Respiratory Infections
However, children with muscle weakness remain at risk for recurrent respiratory infection and atelectasis. [ncbi.nlm.nih.gov]
Children with this form of SMA face a difficult battle and many die from recurrent respiratory infections within the first year of life. However, with new therapies, some children live into their teens or early adulthood. [ucsfbenioffchildrens.org]
Recurrent respiratory infections: Tongue fasciculation and ineffective swallowing may predispose patients to frequently aspirate their food. [symptoma.com]
Pediatric Disease
The FDA also awarded the manufacturer a rare pediatric disease priority review voucher, under a program intended to encourage the development of new drugs and biological products for the prevention and treatment of certain rare pediatric diseases. [fda.gov]
Food and Drug Administration (FDA) granted the application for onasemnogene abeparvovec-xioi for fast track, breakthrough therapy, priority review, and orphan drug designations.[3] The FDA also awarded the manufacturer a rare pediatric disease priority [en.wikipedia.org]
KEYWORDS: Distal neuropathy; IGHMBP2; Respiratory distress; SMARD1; Spinal muscular atrophy with respiratory distress [ncbi.nlm.nih.gov]
"The Natural Course of Infantile Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1)". Pediatrics. 129 (1): e148–e156. doi:10.1542/peds.2011-0544. PMID 22157136. [en.wikipedia.org]
Constipation and gastroesophageal reflux are frequent. Etiology Around 95% of cases of SMA are caused by homozygous deletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein. [orpha.net]
Therefore, constipation, poor nutrition, and drooling are common. Respiratory muscle weakness frequently leads to pneumonia, which can be life threatening. [nationwidechildrens.org]
The most common side effects found in participants in the clinical trials on Spinraza were upper respiratory infection, lower respiratory infection and constipation. [fda.gov]
The most common side effects found in patients in the clinical trials were upper respiratory infection, lower respiratory infection, and constipation, the FDA said. [bostonglobe.com]
Constipation should be treated aggressively as it may lead to discomfort, more problems with gastric emptying, decreased appetite, and reflux. The Portal's Constipation has management information. [medicalhomeportal.org]
Dysphagia. 2010 Sep;25(3):261-4. doi: 10.1007/s00455-009-9269-1. Epub 2010 Jan 20. Author information 1 Department of Occupational Therapy, Gangnam Severance Hospital, Yonsei University, Gangnam-gu, Seoul, 135-720, Republic of Korea. [ncbi.nlm.nih.gov]
Dysphagia may be present. Most children are confined to a wheelchair by age 2 to 3 yr. The disorder is often fatal in early life, frequently resulting from respiratory complications. [merckmanuals.com]
Dysphagia may be present. Most children are confined to a wheelchair by age 2 to 3 years. The disorder is often fatal in early life, frequently resulting from respiratory complications. [msdmanuals.com]
Delayed Gastric Emptying
Specialty Collaborations & Other Services Gastro-Intestinal & Bowel Function Gastrointestinal problems such as reflux, delayed gastric emptying, and constipation are common. [medicalhomeportal.org]
Abdominal Mass
Herein, we report a 4-month-old male infant who presented to our hospital with an abdominal mass that was diagnosed as neuroblastoma and spinal muscular atrophy type I. [ncbi.nlm.nih.gov]
Jaw & Teeth
Fasciculation of the Tongue
The child presented at two months of life with intense muscle weakness affecting predominantly proximal portions of the limbs, especially the legs, muscle hypotonia, fasciculation of the tongue, and severe respiratory muscle involvement. [ncbi.nlm.nih.gov]
Subcutaneous Nodule
Mutations of N-acylsphingosine amidohydrolase 1 are known to separately cause Farber disease (arthritis, subcutaneous nodules, and dysphonia) or SMA with progressive myoclonic epilepsy. [ncbi.nlm.nih.gov]
Reduced Fetal Movement
We present a male patient with SMAX2 who presented with typical symptoms at birth, preceded by reduced fetal movements in the second and third trimesters of pregnancy. [ncbi.nlm.nih.gov]
There may be a history of reduced fetal movements in utero. Mortality/morbidity : median survival is 7 months - 95% die before 18 months. SMA type II Age of onset : 6-18 months. Features : developmental motor delay (delay in sitting, standing). [patient.info]
Muscular Atrophy
[…] known as English spinal muscular atrophy rare congenital neuromuscular disorder spinal muscle atrophy survival motor neuron spinal muscular atrophy spinal muscular atrophies of childhood Spinal muscular atrophy Statements spinal-muscular-atrophy-pro [wikidata.org]
Sumner, Molecular Mechanisms of Spinal Muscular Atrophy, Journal of Child Neurology, 10.1177/0883073807305787, 22, 8, (979-989), (2016). Charlotte J. Sumner, Therapeutics development for spinal muscular atrophy, NeuroRX, 3, 2, (235), (2006). [doi.org]
Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. [ncbi.nlm.nih.gov]
Related Medscape Reference topics: Focal Muscular Atrophies Spinal Muscle Atrophy Spinal Muscular Atrophy Related Medscape resource: Resource Center Spinal Disorders Pathophysiology Spinal muscular atrophy (SMA) is caused by successive motor unit degeneration [emedicine.medscape.com]
Some years later, his two older teenage brothers presented with proximal muscle weakness. Neurophysiology, muscle biopsy and DNA studies confirmed spinal muscular atrophy. [ncbi.nlm.nih.gov]
• Individuals with SMA Type IV develop symptoms after age 21 years, with mild to moderate leg muscle weakness and other symptoms. [ninds.nih.gov]
The types differ in age of onset and severity of muscle weakness; however, there is overlap between the types. [malacards.org]
In the first days of the patient's life, fractures of the right femur and right humerus were found; however, calcium-phosphate metabolism and densitometric examination were normal. [ncbi.nlm.nih.gov]
Devices Market Size, Share & Industry Analysis, By Product Type (Cervical Devices, Thoracolumbar Devices, Interbody Devices, and Biologics), By Disease Indication (Degenerative Disc Disease, Complex Deformity, Traumas & Fractures, and Others), By End [globenewswire.com]
Owing to the similar clinical features of SMA and congenital myopathy, an electrodiagnostic study and muscle biopsy could create confusion in the correct diagnosis in some cases. [ncbi.nlm.nih.gov]
Differential diagnosis Differential diagnoses include SMA2, congenital muscular dystrophies, congenital myopathies, some early-onset mitochondrial disorders, and carbohydrate metabolism disorders (see these terms). [orpha.net]
Nasal ventilation in congenital myopathies and spinal muscular atrophies. Eur Respir Rev. 1993 ;3: 275 - 278. Google Scholar Simonds AK, Ward S., Heather S., et al. [doi.org]
Differential diagnosis Motor neurone disease Primary lateral sclerosis Muscular dystrophy Congenital myopathies Disorders of carbohydrate metabolism ( glycogen storage diseases ) Myasthenia gravis Poliomyelitis Investigations Blood tests Creatine kinase [patient.info]
Joint Deformity
Farber disease is associated with joint deformities, lipomatous skin nodules, and often is fatal by 2-3 years of age; while SMA-PME is characterized by childhood-onset motor neuron disease and progressive myoclonic epilepsy. [ncbi.nlm.nih.gov]
People with this condition may experience the following symptoms: Joint deformities that impede mobility Infants may be born with broken bones Kennedy's disease is one type of X-linked spinal muscular atrophy. [cedars-sinai.edu]
Affected infants move less in the womb, and as a result they are often born with joint deformities (contractures). They have extremely weak muscle tone (hypotonia) at birth. [ghr.nlm.nih.gov]
If a child requires surgery for scoliosis or other joint deformities, intensive preoperative and postoperative physical therapy can help prevent respiratory complications and loss of strength or function. Assistive Devices. [moveforwardpt.com]
Distractibility
We observed a beneficial distraction through the possibility to watch a movie or listen to music during the procedure. In some cases, an additional sedation was necessary. [ncbi.nlm.nih.gov]
She presented with progressive muscle weakness, tremor, seizure, and cognitive impairment. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epilepsy. [ncbi.nlm.nih.gov]
Extremities: Occasional tremors of fingers and muscular fasciculation may be observed in chronic infantile forms of SMA. Pseudohyperthrophy of gastrocnemius muscle (calf muscle) may be seen in SMA II. [symptoma.com]
Fine tremors of the face are present in over 90% of patients. Type 2 diabetes mellitus, hand tremor, and infertility can also occur. [encyclopedia.com]
Unable to Walk
While the father first walked at the age of 19 months, the son was unable to walk at age 3 years. In both, knee and ankle reflexes were absent and sensation was intact. Serum creatine kinase levels were normal. [ncbi.nlm.nih.gov]
Affected children can typically maintain a seated position without support but are unable to walk. SMA type III is often diagnosed between 18 months and three years of age. [babysfirsttest.org]
Some people may even be paralyzed or unable to walk or move parts of their body. Even so, with the right care, most people affected by spina bifida lead full, productive lives. Learn about living with spina bifida at different ages » [cdc.gov]
[…] to walk at the time of diagnosis. [jamanetwork.com]
Type II SMA is characterized by onset of muscle weakness and hypotony usually after six months of age; the children are able to sit but unable to walk unaided. [doi.org]
Areflexia
Infantile X-linked spinal muscular atrophy (SMAX2) is a rare form of spinal muscular atrophy manifesting as severe hypotonia, areflexia, arthrogryposis, facial weakness and cryptorchidism, and frequently accompanied by bone fractures. [ncbi.nlm.nih.gov]
Some of the symptoms include: muscle weakness poor muscle tone weak cry limpness or a tendency to flop difficulty sucking or swallowing accumulation of secretions in the lungs or throat legs that tend to be weaker than the arms hypotonia, areflexia, and [wikidoc.org]
Therefore, damage to lower motor neurons will subsequently result in hyporeflexia and/or areflexia.[1] Note that, in spinal shock, which is commonly seen in the transection of the spinal cord (Spinal cord injury), areflexia can transiently occur below [en.wikipedia.org]
Other symptoms include: Muscle atrophy Muscle weakness Areflexia Trouble Breathing Thin muscle mass Trouble eating or swallowing Lack of head and neck control Involuntary facial twitching Atrophic muscle changes Muscle twitching Sensory neuropathies Difficulty [stemcellthailand.org]
Limb Weakness
As the disease progresses patients may notice limb weakness starting in the pelvis or shoulders, or weakness of the facial and tongue muscles. Symptoms of SMA-LED often develop in infancy or early childhood. [cedars-sinai.edu]
There is a clinical variant of SMA, known as autosomal-dominant spinal muscular atrophy characterized by a predominantly lower limb weakness and muscle wasting. [symptoma.com]
In addition to muscle weakness, clinical features include head lag, poor sucking and swallowing, weak cry, proximal limb weakness, and lack of reflexes. Affected children never raise their head, roll over, or walk. [encyclopedia.com]
Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is characterized by degeneration of the anterior horn cells of the spinal cord, which leads to the axial and limb weakness associated with muscle atrophy. [dict.cnki.net]
Absent Deep Tendon Reflex
Other symptoms may include: Decreased or absent deep tendon reflexes, such as the relfex that occurs when you tap on your knee. [ucsfbenioffchildrens.org]
Signs of motor neuron disease such as muscle weakness, muscle atrophy, fasciculations, and reduced or absent deep tendon reflexes can be seen. [medlink.com]
The following workup and testing methods are implored in cases of spinal muscular atrophy:
A genetic panel for SMN 1 sequencing and coding is amply suggested in cases of infantile SMA suspects [8]. Amniocentesis of the fetal chorionic villi has a sensitivity rating of 88% to 99% in the prenatal diagnosis of SMA. Recent studies reveal that carrier detection rating for SMA may rise to 90% [9].
The laboratory determination of creatine kinase (CK) level may be a helpful tool in a comprehensive SMA work up. Type 1 SMA will arbitrarily present with a normal CK level while the other forms may show CK elevations.
The use of an electromyography (EMG) and nerve conduction studies may be helpful in the diagnosis of SMA. Muscles which are not clinically affected will show signs of denervation with EMG while nerve conduction remains normal.
There is no available cure for SMA to date. However, there are supportive treatment options to allay the discomforts that inherently affect the SMA patients:
Physical therapy exercises may help delay progression of SMA leading to muscular atrophy.
Appliance or Equipment: This are mechanical aids like splints, bracing and spinal orthoses to help SMA patients to go about their daily chores [10].
Surgical correction of exaggerated scoliosis.
Gastrostomy placement on infants with SMA type 1.
The relative morbidity and mortality rates of SMA varies inversely with age of onset. The SMA type 1 in Werdnig-Hoffman disease carries the worst prognosis with a very high mortality rate. Life expectancy of the patient is usually unaffected with the milder forms of SMA (type 3 and type 4).
Some genetic studies point to prognosticate prenatal occurrence of SMA via amniocentesis. The findings of severe SMA by genetic studies may give some mothers the option for therapeutic abortion in some liberal countries.
The following clinical disorders are the established complications associated with spinal muscular atrophy:
Difficulty in feeding: This is due to the inability of the infants to suck and swallow in infantile cases of SMA.
Recurrent respiratory infections: Tongue fasciculation and ineffective swallowing may predispose patients to frequently aspirate their food.
Bed sores: Long term paraplegia may lead to pressure sores
Spinal muscular atrophy is transmitted via an autosomal-recessive gene from both parents, meaning the mother and the father will not convey any symptoms of the disease. The offspring will carry the SMA gene defect through a homozygous deletion type of inheritance.
The inherited genetic defects on chromosome 5q11.2-13.3 are generally associated with spinal muscular atrophy type 1 to 3 [1]. Defects in genetic SMA are not exclusive to peripheral nerves but it involves the central nervous system (CNS) as well. There is a clinical variant of SMA, known as autosomal-dominant spinal muscular atrophy characterized by a predominantly lower limb weakness and muscle wasting [2].
In the United States, SMA represent the next most common autosomal-recessive genetic disorder following cystic fibrosis. The acute form of SMA in infants occurs in 1 out of 10,000 live births, while the chronic SMAs becomes evident in 1 out of 24,000 births. The chronic infantile type of SMA accounts to 50% of all cases [3].
Spinal muscular atrophy expresses in 1 out of 10,000 live births worldwide [4]. The mortality rate of acute infantile SMA (type 1) reaches 95% with a 7 month mean survival average.
The leading cause of mortality is the complication of severe respiratory infections in SMA. There is a predilection of SMA among males especially in both infantile onset types [5].
The familial spinal muscular atrophy is represented by two survival motor neurons (SMN1 and SMN2) [6]. In more than 95% of SMA cases there has been an evident homozygous gene disruption in SMN1 on the small arm loci of chromosome 5q.
These pathologic phenomenon is grossly brought about by spontaneous mutation and gene deletion. The missing SMN1 in the genetic defect will allow SMN2 to generate the missing protein for the spinal cord development although it can only come up with 10% of the actual protein chain length [7].
Genetic counselling for carrier parents may avert the emergence of an affected sibling. The prenatal amniocentesis of the fetal chorionic villus may help attending physicians prepare for any untoward eventualities during the baby's delivery. Prompt diagnosis and early intervention is the key in reducing morbidity and mortality.
Spinal muscular atrophy or SMA is a hereditary disease characterized by progressive musclar weakness due to deterioration of the lower motor neuron (anterior horn) cells of the spinal cord including the motor nuclei of the central nervous system (brainstem).
The pathology is mainly on the motor neurons connecting the spinal cord and the brain to the muscles of the body. The more common types of spinal muscular atrophy include: Werdnig-Hoffman disease or SMA type 1 (infantile type of acute onset), SMA type 2 (chronic infantile type), Kugelberg-Welander disease or SMA type 3 (chronic juvenile onset), and the SMA type 4 (adult onset).
Spinal muscular atrophy or SMA is a hereditary disease characterized by the progressive musclar weakness due to the deterioration of the lower motor neuron (anterior horn) cells of the spinal cord including the motor nuclei of the central nervous system (brainstem).
It is due to autosomal-recessive genetic inheritance.
Sucking and swallowing ability, tremors, weak abdominal muscles and respiratory difficulty are the usual symptoms
Patients diagnosed with spinal muscular atrophy should be submitted to rigorous pediatric neurology follow-ups for the early classification of the disease.
Treatment and follow up
The third and fourth type of SMA may be compatible to normal living till adulthood. Offspring from patients who make it to adulthood may carry the recessive gene and should be subjected to parental genetic counselling in the future.
Burlet P, Burglen L, Clermont O, et al. Large scale deletions of the 5q13 region are specific to Werdnig- Hoffmann disease. J Med Genet. Apr 1996;33(4):281-3
Oates EC, Reddel S, Rodriguez ML, Gandolfo LC, Bahlo M, Hawke SH, Lamandé SR, Clarke NF, North KN. Autosomal dominant congenital spinal muscular atrophy: a true form of spinal muscular atrophy caused by early loss of anterior horn cells. Brain. 2012; 135(Pt 6):1714-23 (ISSN: 1460-2156)
Harding AE. Inherited neuronal atrophy and degeneration predominantly of lower motor neurons. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 3rd ed. Philadelphia: WB Saunders; 1993:1051-64
Pearn J. Classification of spinal muscular atrophies. Lancet. Apr 26 1980; 1(8174):919-22.
Hausmanowa-Petrusewicz I, Zaremba J, Borkowska J, Szirkowiec W. Chronic proximal spinal muscular atrophy of childhood and adolescence: sex influence. J Med Genet. Dec 1984; 21(6):447-50.
Martínez-Hernández R, Bernal S, Also-Rallo E, Alías L, Barceló MJ, Hereu M, Esquerda JE, Tizzano EF. Synaptic defects in type I spinal muscular atrophy in human development.J Pathol. 2013; 229(1):49-61 (ISSN: 1096-9896)
Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. Jun 21 2008; 371(9630):2120-33.
Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol. May 2012; 11(5):443-52.
Ben-Shachar S, Orr-Urtreger A, Bardugo E, Shomrat R, Yaron Y. Large-scale population screening for spinal muscular atrophy: clinical implications.Genet Med. 2011; 13(2):110-4 (ISSN: 1530-0366)
Armon C. ALS 1996 and Beyond: New Hopes and Challenges. A manual for patients, families and friends. 3rd ed. Loma Linda, Calif: 2000:18.