Snyder–Robinson syndrome (SRS) is an extremely rare inherited genetic disorder[1] characterized by muscular and skeletal abnormalities, varying degrees of intellectual disability, seizures,[2] and slow development.[3]
SRS is caused by a mutated SMS gene at chromosome Xp21.3-p22.12, which carries instructions for producing the enzyme spermine synthase.[4] Spermine synthase in turn helps the body produce spermine, a polyamine critical to cell processes such as cell division, tissue repair, and apoptosis.[5] The resulting shortage of spermine in cells causes problems with development and brain function, though the exact mechanism is not understood.
The syndrome has also been referred to as Snyder–Robinson X-linked mental retardation syndrome (MRXSSR) and spermine synthase deficiency. SRS exclusively affects males.[1] Only about ten families currently have a child with SRS, and 50 people have been diagnosed worldwide since 1969.[6]
Presentation
Snyder–Robinson usually is noticeable in infants, causing hypotonia and declining muscle tone with age. Seizures can occur in childhood, and children are especially susceptible to broken bones.[3]
During early childhood, SRS causes mild to profound intellectual disability; speech difficulties; problems with walking; osteoporosis; marfanoid habitus; and scoliosis, kyphosis, or both (kyphoscoliosis). Distinctive facial features include a cleft palate, facial asymmetry, and a prominent lower lip. Kidney problems may also occur, such as nephrocalcinosis and renal cysts.[citation needed]
Cause
SRS is a recessive X-linked condition.[7] There are no known female cases, as both copies of the X chromosome would need to be mutated.[citation needed]
Diagnosis
When SRS is suspected, doctors will order a molecular genetic test to confirm a mutation in the SMS gene—specifically a "hemizygous loss-of-function... pathogenic variant". However, there are currently no formal criteria for a diagnosis.[3]
Management
Individuals with Snyder–Robinson may be assisted by occupational therapy, physical or speech therapy. Anti-seizure medications such as carbamazepine, phenobarbital, and clobazam can be used to manage seizures[2]—the medication used often is influenced by the type of seizure. Bone density can be determined via a DXA scan and may be improved with calcium supplements.[3]
In 2014, several parents of individuals with SRS founded the Snyder–Robinson Foundation, a 501(c)(3) non-profit based in the US.[8][6] It is a member of the National Organization for Rare Disorders.[9]
History
SRS was first reported in a 1969 paper published in Clinical Pediatrics by Russell D. Snyder[10] and Arthur Robinson, who described the syndrome as "recessive sex-linked mental retardation in the absence of other recognizable abnormalities".