P.294 - An unclassified congenital myopathy diagnosed as Snyder Robinson syndrome identified through the deciphering developmental disorders study

Abstract

Snyder Robinson syndrome (SRS) (OMIM #309583) is a rare X-linked intellectual disability syndrome characterised by thin habitus, reduced muscle mass, osteoporosis, kyphoscoliosis, facial asymmetry and intellectual disability. The causative gene is the spermine synthase gene (SMS) located on the X chromosome. Boys with SRS have previously been shown to have a decreased spermine to spermidine ratio. Spermine is a polyamine and its reduction is thought to be responsible for the phenotypic effects associated with SRS. Polyamines have essential roles in cell physiology including gene expression, nucleic acid and protein synthesis and protection from oxidative damage. Less than twenty clinical cases of individuals with SRS have been reported previously in the literature all with novel or familial mutations identified. Boys with SRS have a spectrum of severity with inter-familial variability suggesting some genotype phenotype correlation. We report a new case of Snyder-Robinson Syndrome identified through the Deciphering Developmental Disorders (DDD) study with a missense variant (c.335C>T, P112L) in the SMS gene. This variant has been previously studied, but clinical details are not available. Our patient presented at 6 weeks of age with hypotonia, plagiocephaly and facial asymmetry. At 4 years had myopathic face, high arched palate, marked scoliosis, had an accessory nipple, wide-based gait, Gower's negative and flat feet. At 10 years of age he has a severe thoracic scoliosis, has had femoral fractures, focal seizures, and has mild developmental and speech delay. Standard neurological investigations (EEG abnormal, normal NCS, MRI brain and spine)were done. He has had two muscle biopsies with findings suggestive of congenital myopathy or mitochondrial cytopathy. SRS is likely to be underdiagnosed in the neuromuscular cohort. Next generation sequencing studies are anticipated to identify new cases.