Medicine:Snyder–Robinson syndrome

From HandWiki
Snyder–Robinson syndrome
Other namesSpermine synthase deficiency
SymptomsIntellectual disability, facial asymmetry, kyphoscoliosis, osteoporosis, hypotonia, asthenic build, seizures
Usual onsetAdolescence, childhood, infancy
CausesGenetic[1]
Differential diagnosisGlycerol kinase deficiency, Urban syndrome, Rett syndrome, cerebral palsy, Prader–Willi syndrome
Frequency<1 per 1,000,000

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.

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]

Cause

SRS is a recessive X-linked condition.[8] There are no known female cases, as both copies of the X chromosome would need to be mutated.

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.[9][6] It is a member of the National Organization for Rare Disorders.[10]

History

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]

References

  1. 1.0 1.1 1.2 "Snyder-Robinson syndrome". NIH. https://ghr.nlm.nih.gov/condition/snyder-robinson-syndrome. Retrieved 1 July 2019. 
  2. 2.0 2.1 Rosato, Donna (June 21, 2017). "Who's on Medicaid Might Surprise You". Consumer Reports. https://www.consumerreports.org/medicaid/whos-on-medicaid-might-surprise-you/. Retrieved 1 July 2019. 
  3. 3.0 3.1 3.2 3.3 Albert, Jessica; Schwartz, Charles E.; Boerkoel, Cornelius F.; Stevenson, Roger E. (June 27, 2013). "Snyder-Robinson Syndrome". GeneReviews (Seattle: University of Washington, Seattle). PMID 23805436. https://www.ncbi.nlm.nih.gov/books/NBK144284/. Retrieved 1 July 2019. 
  4. Cason, A. Lauren; Ikeguchi, Yoshihiko; Skinner, Cindy; Wood, Tim C.; Holden, Kenton R.; Lubs, Herbert A.; Martinez, Francisco; Simensen, Richard J. et al. (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. 
  5. Murray-Stewart, Tracy; Dunworth, Matthew; Foley, Jackson R.; Schwartz, Charles E.; Casero, Jr., Robert A. (7 December 2018). "Polyamine Homeostasis in Snyder-Robinson Syndrome". Medical Sciences. Polyamine Metabolism in Disease and Polyamine-Targeted Therapies 6 (4): 112. doi:10.3390/medsci6040112. ISSN 2076-3271. PMID 30544565. 
  6. 6.0 6.1 Gilreath, Ariel (March 10, 2018). "GGC hopes to create model for researching rare diseases". The Index-Journal. https://www.indexjournal.com/news/ggc-hopes-to-create-model-for-researching-rare-diseases/article_e7af0042-7672-5502-9baf-b8ab6a4258b0.html. Retrieved 1 July 2019. 
  7. "Snyder-Robinson syndrome". https://rarediseases.info.nih.gov/diseases/5615/snyder-robinson-syndrome. 
  8. "X-linked intellectual disability, Snyder type". https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=3063. Retrieved 1 July 2019. 
  9. Miranda, Coty Dolores (January 13, 2019). "Dr. Mary Jo Kutler closes out cherished practice". Ahwatukee Foothills News. http://www.ahwatukee.com/business/article_fa1de4a2-15c9-11e9-abfe-4bfb7816c240.html. Retrieved 1 July 2019. 
  10. "About Us". 2019-06-15. https://snyder-robinson.org/about-us-2/. Retrieved 1 July 2019. 
  11. Snyder, Russell D. (July 1, 1968). "Facial Palsy Following Measles Vaccination, a Possible Connection". Pediatrics 42 (1): 215–216. ISSN 0031-4005. PMID 5657694. https://pediatrics.aappublications.org/content/42/1/215.3.long. 
  12. 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. 

External links

Classification
External resources