[Autosomal dominant mental retardation type 5 caused by

Area of Science:

• Genetics
• Pediatrics
• Neurology

Background:

• Autosomal dominant mental retardation type 5 is associated with SYNGAP1 gene mutations.
• Understanding the clinical and genetic profiles of affected children is crucial for diagnosis and management.

Approach:

• Retrospective analysis of 8 children diagnosed with SYNGAP1-related autosomal dominant mental retardation type 5.
• Literature review of 48 Chinese children with SYNGAP1 mutations.

Key Points:

• Early onset (mean 9 months) of moderate-to-severe developmental delay, particularly language, and seizures (7/8 children).
• Common mutations include novel heterozygous frameshift and nonsense mutations; 6p21.3 microdeletion also observed.
• In a larger cohort (48 children), seizures affected 40, with a mean onset age of 31.4 months. Frameshift (31%) and nonsense (40%) mutations were prevalent.

Conclusions:

• SYNGAP1 mutations lead to early-onset developmental delays and frequent seizures in children.
• Frameshift and nonsense mutations are the predominant genetic alterations.
• Valproic acid demonstrates significant efficacy in managing seizures, with 85% responding and 48% achieving complete control with monotherapy or combination therapy.