Autosomal dominant primary microcephaly

Autosomal dominant primary microcephaly (also known as autosomal dominant microcephaly) is a rare genetic condition characterized by a significantly reduced head circumference (more than 2-3 standard deviations below the mean for age and sex) that is present at birth or becomes apparent in early infancy. Unlike the more commonly described autosomal recessive forms of primary microcephaly (MCPH), the autosomal dominant form is inherited from an affected parent carrying a single copy of a pathogenic variant. The condition primarily affects the central nervous system, with the brain being disproportionately small (micrencephaly) due to impaired neuronal proliferation or migration during fetal development. Clinical features vary in severity but typically include reduced head circumference, mild to moderate intellectual disability, and in some cases relatively preserved cognitive function. Some affected individuals may have a sloping forehead and simplified gyral patterns on brain imaging, though the brain architecture may otherwise appear normal. Short stature may be present in some families. The degree of intellectual impairment is generally milder compared to autosomal recessive primary microcephaly, and some individuals may function within the low-normal range of intelligence. There is currently no cure or specific targeted therapy for autosomal dominant primary microcephaly. Management is supportive and multidisciplinary, focusing on developmental assessments, early intervention programs, speech and occupational therapy, and educational support tailored to the individual's cognitive abilities. Genetic counseling is important for affected families, as each child of an affected individual has a 50% chance of inheriting the condition. Regular neurological follow-up and monitoring of developmental milestones are recommended.

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