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Rett Syndrome, congenital variant - FOXG1

Clinical Features

Recently, the FOXG1 gene was implicated in the molecular etiology of the congenital variant of Rett syndrome in patients negative for CDKL5/MECP2 mutations. Children show persistent hypotonia, neurological symptoms with poor reactivity, and irritability. At birth, head circumference was normal while a deceleration of growth was recognized soon afterwards, leading to severe microcephaly (up to - 3SD). Motor development was severely impaired and voluntary hand use was absent. In contrast with classic Rett, patients showed poor eye contact. Stereotypic hand movements were present continuously, some patients showed abnormal movements of the tongue and jerky movements of the limbs. Most patients present with strabism. Brain magnetic resonance imaging showed corpus callosum hypoplasia in most cases, while epilepsy was a variable sign. Scoliosis was present and severe in the older patients. Neurovegetative symptoms typical of Rett were frequently present.

Severe encephalopathy, microcephaly and Rett-like features can occur not only in girls but also and boys.

Genetic Information

Forkhead box G1 (FOXG1) is a transcription factor a that is critical for forebrain development, where it promotes progenitor proliferation and suppresses premature neurogenesis. The encoding gene FOXG1 is located on chromosome 14 (14q13).

Diagnostic