Genetic Microcephaly in a Saudi Population: Unique Spectrum of Affected Genes Including a Novel One

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Genetic microcephaly increases risk for developmental disabilities, epilepsy, and motor impairment.
• Understanding genetic causes is crucial for diagnosis and management.

Purpose of the Study:

• To detail the genetic causes, clinical features, and imaging findings of microcephaly in Saudi Arabian patients.
• To identify common and novel genetic etiologies.

Main Methods:

• Retrospective chart review of 128 referred patients.
• Collection of demographic, clinical, laboratory, radiological, and molecular data.
• Genetic analysis to identify causative mutations.

Main Results:

• 52% of cases had identifiable genetic causes, primarily monogenic (92%).
• Developmental disability (84%), epilepsy (56%), and motor impairment (50%) were prevalent.
• ASPM gene mutations were most common (19%); a novel PLK1 mutation was identified in 6% of cases.

Conclusions:

• Single gene defects, particularly ASPM, are a major cause of genetic microcephaly in this population.
• Hereditary neurometabolic disorders are a frequent contributor.
• PLK1 gene mutations are proposed as a potential novel cause of genetic microcephaly.