Acquired microcephaly, regression of milestones, mitochondrial dysfunction, and episodic rigidity in a 46,XY male with a de Novo MECP2 gene mutation

We report a case of acquired microcephaly in a male infant. Testing for mutations in the MECP2 gene identified a de novo hemizygous c.378-3C>G mutation at a highly conserved 3′ splice site, consistent with Rett syndrome. Other distinctive features included periodic hypertonicity, decreased mitochondrial complex III activity, and abnormal magnetic resonance imaging (MRI) T2 signal in the pons. Rett syndrome was originally described in females with a clinical phenotype of deceleration of head growth, abnormal hand movements, and developmental regression. The clinical diagnosis can now be supported by genetic testing for MECP2 mutations, and the phenotype of disorder has expanded. Cases of Rett syndrome in males are rare and a total of 17 such cases have been reported. This case extends the clinical phenotype of Rett syndrome in males and associates this mutation with mitochondrial dysfunction.