Snyder-Robinson syndrome
Snyder-Robinson syndrome is a rare, X-linked condition occurring exclusively in males, characterized by intellectual disability, muscle weakness, and skeletal abnormalities.
Overview
This condition affects development from early childhood, with intellectual disability ranging from mild to profound. Speech development is often delayed or absent. Affected males typically exhibit an asthenic habitus, characterized by a thin frame and low muscle mass.
Symptoms
- Muscle and Motor: Weakness or "floppiness" (hypotonia) in infancy, which progresses with age, often resulting in an unsteady gait.
- Skeletal: Thinning of the bones (osteoporosis) leading to frequent fractures, and abnormal curvature of the spine (kyphoscoliosis). Affected individuals are typically shorter than their peers.
- Facial and Physical: A long face, a high-arched roof of the mouth or cleft palate, and facial asymmetry.
- Other: Seizures, as well as potential abnormalities of the genitalia and kidneys.
Causes
Snyder-Robinson syndrome results from mutations in the SMS gene, which provides instructions for the enzyme spermine synthase. This enzyme is responsible for producing spermine, a polyamine molecule critical for cell growth, division, and the normal function of the brain, muscles, and bones. A deficiency in spermine synthase disrupts these essential cellular processes.
Inheritance
This condition is inherited in an X-linked recessive pattern. Because the SMS gene is located on the X chromosome, males—who have only one X chromosome—are affected if they inherit a single altered copy of the gene. Females, who have two X chromosomes, would require mutations in both copies to be affected; no cases in females have been reported.