Snyder-Robinson syndrome

Snyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males.

Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech.

Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or "floppiness" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait.

Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.

Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys.

Snyder-Robinson syndrome is a rare condition; its prevalence is unknown. About 10 affected families have been identified worldwide.

Snyder-Robinson syndrome results from mutations in the SMS gene. This gene provides instructions for making an enzyme called spermine synthase. This enzyme is involved in the production of spermine, which is a type of small molecule called a polyamine. Polyamines have many critical functions within cells. Studies suggest that these molecules play roles in cell growth and division, the production of new proteins, the repair of damaged tissues, the function of molecules called ion channels, and the controlled self-destruction of cells (apoptosis). Polyamines appear to be necessary for normal development and function of the brain and other parts of the body.

Mutations in the SMS gene greatly reduce or eliminate the activity of spermine synthase, which decreases the amount of spermine in cells. A shortage of this polyamine clearly impacts normal development, including the development of the brain, muscles, and bones, but it is unknown how it leads to the specific signs and symptoms of Snyder-Robinson syndrome.

Genetic Testing Information

• Genetic Testing Registry: Syndromic X-linked intellectual disability Snyder type

Genetic and Rare Diseases Information Center

• X-linked intellectual disability, Snyder type

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNYDER-ROBINSON TYPE; MRXSSR

Scientific Articles on PubMed

• PubMed

• Albert JS, Bhattacharyya N, Wolfe LA, Bone WP, Maduro V, Accardi J, Adams DR, Schwartz CE, Norris J, Wood T, Gafni RI, Collins MT, Tosi LL, Markello TC, Gahl WA, Boerkoel CF. Impaired osteoblast and osteoclast function characterize the osteoporosis of Snyder - Robinson syndrome. Orphanet J Rare Dis. 2015 Mar 7;10:27. doi: 10.1186/s13023-015-0235-8. Citation on PubMed or Free article on PubMed Central
• Becerra-Solano LE, Butler J, Castaneda-Cisneros G, McCloskey DE, Wang X, Pegg AE, Schwartz CE, Sanchez-Corona J, Garcia-Ortiz JE. A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am J Med Genet A. 2009 Mar;149A(3):328-35. doi: 10.1002/ajmg.a.32641. Citation on PubMed or Free article on PubMed Central
• Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE. X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003 Dec;11(12):937-44. doi: 10.1038/sj.ejhg.5201072. Citation on PubMed
• de Alencastro G, McCloskey DE, Kliemann SE, Maranduba CM, Pegg AE, Wang X, Bertola DR, Schwartz CE, Passos-Bueno MR, Sertie AL. New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome. J Med Genet. 2008 Aug;45(8):539-43. doi: 10.1136/jmg.2007.056713. Epub 2008 Jun 11. Citation on PubMed
• Peron A, Spaccini L, Norris J, Bova SM, Selicorni A, Weber G, Wood T, Schwartz CE, Mastrangelo M. Snyder-Robinson syndrome: a novel nonsense mutation in spermine synthase and expansion of the phenotype. Am J Med Genet A. 2013 Sep;161A(9):2316-20. doi: 10.1002/ajmg.a.36116. Epub 2013 Jul 29. Erratum In: Am J Med Genet A. 2014 Apr;164A(4):1083. Citation on PubMed
• Schwartz CE, Wang X, Stevenson RE, Pegg AE. Spermine synthase deficiency resulting in X-linked intellectual disability (Snyder-Robinson syndrome). Methods Mol Biol. 2011;720:437-45. doi: 10.1007/978-1-61779-034-8_28. Citation on PubMed
• Zhang Z, Norris J, Kalscheuer V, Wood T, Wang L, Schwartz C, Alexov E, Van Esch H. A Y328C missense mutation in spermine synthase causes a mild form of Snyder-Robinson syndrome. Hum Mol Genet. 2013 Sep 15;22(18):3789-97. doi: 10.1093/hmg/ddt229. Epub 2013 May 21. Citation on PubMed or Free article on PubMed Central