Modifier, X-Linked, For Neurofunctional Defects

Clinical Features

Several disorders affecting speech, learning and behavior have a 3:1 or greater male:female ratio. Tourette syndrome (137580), primarily caused by an autosomal gene, is such a condition. Comings and Comings (1985) analyzed family pedigrees of 430 consecutive cases and concluded that a model that proposed a modifier gene on the X chromosome better fits the observed frequency of affected sons and daughters according to whether the father or the mother is the transmitter than do either of 2 other models: an autosomal modifier or a developmental model that postulates a difference in the young male versus female brain. Comings and Comings (1985) suggested that the same modifier may be operative in other neurofunctional disorders with a male preponderance.

Molecular Genetics

Lawson-Yuen et al. (2008) identified a hemizygous 757-kb deletion in the NLGN4 gene (300427.0003) in a boy with autism and mental retardation (300495), who also had a motor tic. The patient's 9-year-old brother, who carried diagnoses of Tourette syndrome and attention deficit-hyperactivity disorder with mild cognitive defects, also carried the deletion. The mother, who was a carrier, had a learning disability, depression, and anxiety. Lawson-Yuen et al. (2008) concluded that NLGN4 mutations can be associated with a wide spectrum of neuropsychiatric disorders.