Microcephaly is a neurological condition characterized by occipito-frontal head circumference at birth equal to or less than -2 SD below the mean for sex, age, and ethnicity. Clinical findings may also include abnormal brain structure, cognitive impairment, short stature, craniosynostosis and seizures.
Microcephaly is considered primary, which is present at birth and secondary, which develops postnatally. Both primary microcephaly and secondary microcephaly can be isolated, syndromic or associated with other brain malformations. Genetic conditions with microcephaly involvement include Cornelia de Lange syndrome, Seckel syndrome, Smith-Lemli-Opitz syndrome, syndromes associated with chromosomal abnormatlities, and DNA repair disorders.
The inheritance patterns of microcephaly can be autosomal dominant, recessive or x-linked.
Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis
3. Carrier testing for at-risk relatives
4. Prenatal diagnosis for known familial mutation
5. Genetic counseling
Verloes A et al. Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders. . GeneReviews® 2009 Sept 1 (Updated 2013 Oct 31).
Woods C.G. Human microcephaly. Curr. Opin. Neurobiol. 2004: 14, pp. 112-117.
Yu et al. Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. Nat Genet. 2010;42:1015-20.