Mutations in the ATP7A gene can manifest as three distinct phenotypes related to copper transport dysfunction and are inherited in an X-linked manner. Related biochemical findings are usually present in Menkes disease and Occipital horn syndrome but not in the distal motor neuropathy phenotype.
Individuals with Menkes disease usually become symptomatic around 2-3 months of age. These infants may present with regression of milestones, seizures, hypotonia, failure to thrive, and characteristic changes of the hair. The primary features of occipital horn syndrome include specific bony changes at the site of muscle attachment to the occipital bone. These individuals may have other findings as well including bladder diverticula, inguinal hernias, and lax joints and skin with either normal or slightly reduced intellect.
The related distal motor neuropathy is typically progressive, adult-onset with distal muscle weakness and atrophy in feet and hands. Absent ankle reflexes are common.