Prenatal diagnosis Prenatal diagnosis of<unk>  in high risk pregnancies is doable, but very uncommon and rarely performed. Furthermore, this is only possible if the mutation causing the disease has already been identified within the family genome. There are a few different techniques in which prenatal testing can be carried out. Prenatal testing is usually performed around 15–18 weeks, using amniocentesis to extract DNA from the fetus's cells. Prenatal testing can also be performed during weeks 10–12 using chorionic villus sampling (CVS) to extract DNA from the fetus. Recently, there has been an increased interest in utilizing ultrasound equipment in order to detect fetal skull abnormalities due to immature fusion of the cranial sutures. Clinical diagnosis The overall diagnosis of SCS is primarily based on clinical findings and observations based on dysmorphology examination (assessing structural defects) and radiographic evaluation (X-rays, MRIs, and CT scans). Molecular/genetic diagnosis A clinical diagnosis of SCS can be verified by testing the TWIST1 gene (only gene in which mutations are known to cause SCS) for mutations using DNA analysis, such as sequence analysis, deletion/duplication analysis, and cytogenetics/ FISH analysis. Sequence analysis of exon 1 (TWIST1 coding region) provides a good method for detecting the frequency of mutations in the TWIST1 gene. These mutations include nonsense, missense, splice site mutation, and intragenic deletions/insertions. Deletion/duplication analysis identifies mutations in the TWIST1 gene that are not readily detected by sequence analysis. Common methods include PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA). Cytogenetic/FISH analysis attaches fluorescently labels DNA markers to a denatured chromosome and is then examined under fluorescent lighting, which reveals mutations caused by translocations or inversions involving 7p21. Occasionally, individuals with SCS have a chromosome translocation, inversion, or ring chromosome 7 involving 7p21 resulting in atypical findings, such as, increased developmental delay. Individuals with SCS, typically have normal brain functioning and rarely have mental impairments. For this reason, if an individual has both SCS and mental retardation, then they should have their TWIST1 gene screened more carefully because this is not a normal trait of SCS. Cytogenetic testing and direct gene testing can also be used to study gene/chromosome defects. Cytogenetic testing is the study of chromosomes to detect gains or losses of chromosomes or chromosome segments using fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). Direct gene testing uses blood, hair, skin, amniotic fluid, or other tissues in order to find genetic disorders. Direct gene testing can determine whether an individual has SCS by testing the individual's blood for mutations in the TWIST1 gene. Differential diagnosis Genetic testing allows for a definitive diagnosis because it allows similar conditions to be differentiated from each other based on which gene is mutated. The following table contains conditions similar to SCS: Condition Symptoms Gene SCS Widely spaced eyes, low hairline, drooping eyes, interdigital webbing, deformed ears, crossed eyes, and downward sloping palpebral fissures TWIST1 Robinow-Sorauf syndrome Widely spaced eyes, deviated septum, flat skull posterior, deformed ears, crossed eyes, protruding jaw, and duplication of distal phalanx TWIST1 Muenke Syndrome Widely spaced eyes, enlarged head, hearing loss, flat cheeks, and low-set ears FGFR3 Crouzon Syndrome Widely spaced eyes, short-broad head, hearing loss, bulging eyes, beaked nose, low-set ears, strabismus, protruding chin, and short humerus and femur FGFR2 & FGFR3 Pfeiffer Syndrome Widely spaced eyes, underdeveloped jaw, beaked nose, hearing loss, and bulging eyes FGFR1 & FGFR2 Apert Syndrome Widely spaced eyes, prominent forehead, flat skull posterior, bulging eyes, low-set ears, flat or concave face, short thumb, and webbed fingers FGFR2 Isolated unilateral coronal synostosis Only malformation is the premature fusion of sutures; If left untreated, can lead to facial asymmetry resembling SCS FGFR (any) Baller-Gerold syndrome (BGS) Short broad head, bulging eyes, flat forehead, poikiloderma, radial deformity with reduced number of digits, underdeveloped or missing thumb and radius, and growth retardation RECQL4
Saethre–Chotzen syndrome
Pelger–Huët anomaly
Goldberg–Shprintzen syndrome
Marshall–Smith syndrome
Langer–Giedion syndrome
Bardet–Biedl syndrome
Smith–Magenis syndrome
Schinzel–Giedion syndrome