The portal for rare diseases and orphan drugs

SMS has an estimated prevalence of 1/15,000-25,000 and has been identified worldwide in all ethnic groups, but is probably underdiagnosed. Males and females are affected equally.

Patients have a recognizable clinical picture. Craniofacial features include brachycephaly, frontal bossing, hypertelorism, synophrys, upslanting palpebral fissures, midface hypoplasia, a broad square-shaped face with depressed nasal bridge, an everted upper lip with a ``tented'' appearance, and micrognathia in infancy. Dental anomalies include tooth agenesis and taurodontism. Short stature is common in young patients, with height typically in the normal range as adults. Excess weight and/or obesity in teens and adults are common. Other skeletal anomalies include brachydactyly, scoliosis, 5th-finger clinodactyly, 2/3 toe syndactyly, forearm and elbow limitations, vertebral anomalies, persistent fetal finger pads, and polydactyly. Otolaryngological problems such as velopharyngeal insufficiency, a hoarse deep voice, and vocal cord nodules and polyps are also common; hearing loss (60% of patients) is variable and may be mild to moderate. Ophthalmologic features (>60%) include myopia and iris anomalies and rarely, retinal detachment (often resulting from violent behaviors). Mild to moderate intellectual deficit, significant speech delay, decreased sensitivity to pain, peripheral neuropathy, as well as characteristic sleep disturbances and maladaptive behaviors (outbursts/temper tantrums, attention seeking, aggression, disobedience, distraction, and self-injurious behaviors) are common. Organ malformations (30-40%) include cardiac, renal, urinary tract, and central nervous system (CNS) abnormalities.

SMS is typically a sporadic disorder caused either by a 17p11.2 deletion encompassing the retinoic acid-induced 1 (RAI1) gene (90%) or a mutation of the gene (10%).

Diagnosis is based on initial clinical suspicion followed by molecular confirmation of the genetic defect. Careful history-taking for birth defects, sleep disturbance, delayed milestones, chronic ear infections, self-injurious behaviors, and family history are important to recognize the characteristic features.

Differential diagnoses include Down syndrome, Williams syndrome, brachydactyly-intellectual deficit syndrome (del 2q37), Prader-Willi syndrome, 22q11 deletion syndrome, Sotos syndrome, and 9q34 deletion syndrome (see these terms).

Almost all cases correspond to a single occurrence in a family, but prenatal testing can be offered for at-risk pregnancies. When a chromosomal deletion is identified, parental chromosomal testing is recommended to rule-out any translocation or other rearrangements that might affect the recurrence risk.

Affected patients have a 50% chance of having a child with SMS.

Appropriate assessment of the degree of cognitive, developmental, and behavioral deficits and severity of systemic/organ abnormality is essential for appropriate and specific management. Treatment is symptomatic and may include psychotropics intended to increase attention, decrease hyperactivity and stabilize behavior and treatment for sleep disorders. However, no single regimen has shown consistent efficacy. Careful neurological evaluation including electroencephalogram (EEG) should be performed to assess possible subclinical seizures. Family psychosocial support and counseling are recommended.

Prognosis depends on age of diagnosis, disease severity, and suitability of therapeutic interventions. Data on life expectancy are currently insufficient but patients have lived to more than 80 years of age.