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]
Quick Facts Other names, Specialty ...
Snyder–Robinson syndrome |
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Other names | Spermine synthase deficiency |
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Specialty | Medical genetics |
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Symptoms | Intellectual disability, facial asymmetry, kyphoscoliosis, osteoporosis, hypotonia, asthenic build, seizures |
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Usual onset | Adolescence, childhood, infancy |
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Causes | Genetic[1] |
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Differential diagnosis | Glycerol kinase deficiency, Urban syndrome, Rett syndrome, cerebral palsy, Prader–Willi syndrome |
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Frequency | <1 per 1,000,000 |
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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]
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]
Other symptoms that frequently appear in patients with Snyder-Robinson syndrome include arachnodactyly, decreased muscle mass, disproportionately tall stature, long and narrow face, nasal speech, slender toe, and thick lower lip vermilion.[7]
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]
SRS was first reported in a 1969 paper published in Clinical Pediatrics by Russell D. Snyder[11] and Arthur Robinson, who described the syndrome as "recessive sex-linked mental retardation in the absence of other recognizable abnormalities".[12]
Cason, A. Lauren; Ikeguchi, Yoshihiko; Skinner, Cindy; Wood, Tim C.; Holden, Kenton R.; Lubs, Herbert A.; Martinez, Francisco; Simensen, Richard J.; Stevenson, Roger E.; Pegg, Anthony E.; Schwartz, Charles E. (24 September 2003). "X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome". European Journal of Human Genetics. 11 (12): 937–944. doi:10.1038/sj.ejhg.5201072. PMID 14508504. "About Us". The Snyder-Robinson Foundation. 2019-06-15. Retrieved 1 July 2019. Snyder, Russell D.; Robinson, Arthur (November 1, 1969). "Recessive Sex-Linked Mental Retardation in the Absence of Other Recognizable Abnormalities: Report of a Family". Clinical Pediatrics. 8 (11): 669–674. doi:10.1177/000992286900801114. PMID 5823961. S2CID 32198336.