Snyder-Robinson Syndrome

Excerpt

Clinical characteristics: Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome characterized by asthenic build, facial dysmorphism with a prominent lower lip, kyphoscoliosis, osteoporosis, speech abnormalities, and seizures. Developmental delay usually presents as failure to meet early developmental milestones and then evolves to moderate to profound intellectual disability (which appears to remain stable over time) and variable motor disability. Asthenic habitus and low muscle mass usually develop during the first year, even in males who are ambulatory. During the first decade, males with SRS develop osteoporosis, resulting in fractures in the absence of trauma.

Diagnosis/testing: The diagnosis of SRS is established by identification of a hemizygous loss-of-function SMS pathogenic variant on molecular genetic testing.

Management: Treatment of manifestations: Speech, physical, and/or occupational therapy may be helpful. Standard surgical treatment by craniofacial team for those with cleft palate. Calcium supplementation has slightly improved bone mineral density in a few individuals. Standard management of kyphoscoliosis by orthopedics. Seizures have shown varying responses to anti-seizure medications; carbamazepine, phenobarbital, clobazam, levetiracetam, and valproic acid have been used successfully in some individuals.

Surveillance: Monitor developmental progress and educational needs. Clinical examination and DXA scans to evaluate for progression of osteoporosis and investigate for factures if medically indicated. While receiving calcium supplementation, individuals should be evaluated regularly for ectopic calcification by endocrinology. Clinical examinations for kyphoscoliosis at each visit. Monitor those with seizures as clinically indicated.

Genetic counseling: SRS is inherited in an X-linked manner. If the mother of the proband has a pathogenic variant, the chance of transmitting it in each pregnancy is 50%: Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers (to date, features of SRS have not been observed in heterozygous females). Affected males are not known to reproduce. Once an SMS pathogenic variant is identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.