Menkes disease [OMIM #309400] is characterized by mental retardation, hypotonia, seizures, failure to thrive, vascular tortuosity, wormian bones, metaphyseal spurring, bladder diverticulae, pectus excavatum, skin laxity. Occipital Horn syndrome (OHS) or X-linked Cutis Laxa [OMIM #304150] is characterized by bilateral occipital exostoses of the skull (occipital horns), long neck, high arched palate, long face, high forehead, skin and joint laxity, dysautonomia, bladder diverticula, inguinal hernias, vascular tortuosity, and normal or slightly delayed intelligence. Copper levels are decreased in individuals with this spectrum of copper metabolism impairment (<60µg/dL) and ceruloplasmin levels are also diminished (30-150mg/L). Sequence analysis of the coding region reveals >95% of mutations in males. Approximately 15% of mutations are deletions that may not be identified in a female carrier by sequencing. Recently, intragenic duplications of one or more exons of ATP7A have been reported in approximately 5% of patients with Menkes disease.
Deletions and/or duplications in the ATP7A gene as causative of Menkes disease have been reported.