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Snyder-Robinson syndrome

Rachel Starks; Patricia Kirby; Michael Ciliberto; Marco Hefti

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Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X-linked intellectual disability syndrome (OMIM #390583). First described by Drs. Snyder and Robinson in 1969, this syndrome is characterized by an asthenic body habitus, facial dysmorphism, broad-based gait, and osteoporosis with frequent fractures. We report here a pediatric autopsy of a 4 year old male with a history of intellectual disability, gait abnormalities, multiple fractures, and seizures previously diagnosed with Snyder-Robinson syndrome with an SMS gene mutation (c.831G>T:p.L277F). The cause of death was hypoxic-ischemic encephalopathy secondary to prolonged seizure activity. Although Snyder-Robinson syndrome is rare, the need to recognize clinical findings in order to trigger genetic testing has likely resulted in under diagnosis.


Spermine Synthase, Snyder-Robinson syndrome, Mental Retardation, X-linked, Intellectual Disability


Snyder RD, Robinson A. Recessive sex-linked mental retardation in the absence of other recognizable abnormalities: report of a family. Clin Pediatr (Phila). 1969;8(11):669-74. []. [PMID:5823961]

Cason AL, Ikeguchi Y, Skinner C, et al. X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003;11(12):937-44. []. [PMID:14508504]

Albert J, Schwartz CE, Boerkoel CF, Stevenson RE. Snyder-Robinson syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle: University of Washington; 2013 [cited 2013 Jun 27]. p. 1993-2018. Available from:

Alencastro G, McCloskey DE, Kliemann SE, et 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;45(8):539-43. []. [PMID:18550699]

Becerra-Solano LE, Butler J, Castaneda-Cisneros G, et al. A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am J Med Genet. 2009;149A(3):328-35. []. [PMID:19206178]

Zhang Z, Norris J, Kalscheuer V, et al. A Y328C missense mutation in spermine synthase causes a mild form of Snyder–Robinson syndrome. Hum Mol Genet. 2013;22(18):3789-97. []. [PMID:23696453]

Peron A, Spaccini L, Norris J, et al. Snyder-Robinson syndrome: a novel nonsense mutation in spermine synthase and expansion of the phenotype. Am J Med Genet. 2013;161A(9):2316-20. []. [PMID:23897707]

Arena JF, Schwartz C, Ouzts L, et al. X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp21.3-p22.12. Am J Med Genet. 1996;64(1):50-8. [<50::AID-AJMG7>3.0.CO;2-V]. [PMID:8826448]

Kesler SR, Schwartz C, Stevenson RE, Reiss AL. The impact of spermine synthase (SMS) mutations on brain morphology. Neurogenetics. 2009;10(4):299-305. []. [PMID:19277733]

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. []. [PMID:21318891]

Abela L, Simmons L, Steindl K, et al. N(8)-acetylspermidine as a potential plasma biomarker for Snyder-Robinson syndrome identified by clinical metabolomics. J Inherit Metab Dis. 2016;39(1):131-7. []. [PMID:26174906]








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