Warburg Micro syndrome in a Turkish boy

Area of Science:

• Genetics
• Pediatrics
• Neurology

Background:

• Warburg Micro syndrome is a rare genetic disorder characterized by specific facial anomalies, developmental delays, and neurological issues.
• Genetic mutations, particularly in the RAB3GAP gene, are known causes of Warburg Micro syndrome.
• Consanguinity in parents increases the risk of autosomal recessive genetic disorders.

Observation:

• A 4-year-old Turkish boy with Warburg Micro syndrome presented with ptosis, microphthalmia, microcephaly, spastic diplegia, and hypogenitalism.
• Unique features observed in this patient included significant skin hyperextensibility and joint hypermobility, not previously documented in Warburg Micro syndrome.
• Cerebral atrophy and hypoplasia of the corpus callosum and cerebellum were noted on neuroimaging.

Findings:

• Genetic analysis revealed a homozygous splice donor mutation (748+1G>A) in exon 8 of the RAB3GAP gene.
• This mutation is confirmed as the cause of Warburg Micro syndrome in the affected child.
• The presence of skin and joint hyperextensibility expands the phenotypic spectrum of Warburg Micro syndrome.

Implications:

• This case expands the known clinical features of Warburg Micro syndrome, particularly highlighting skin and joint hyperextensibility.
• Identification of a novel mutation in RAB3GAP provides further insight into the genetic basis of the disorder.
• Understanding the full spectrum of Warburg Micro syndrome is crucial for accurate diagnosis, genetic counseling, and potential therapeutic strategies.