Occipital horn syndrome (OHS), formerly considered a variant of Ehlers–Danlos syndrome, is an X-linked recessive mitochondrial and connective tissue disorder. It is caused by a deficiency in the transport of the essential mineral copper, associated with mutations in the ATP7A gene.

Only about 2/3 of children with OHS are thought to have genetically inherited the disorder; the other 1/3 do not have the disease in their family history. Since the disorder is X-linked recessive the disease affects more males. This is because they do not have a second X chromosome, unlike females, so essentially are lacking the 'backup' copy with proper function. Females are much more likely to be carriers only. For a female to be affected they must carry two defective X chromosomes, not just one.

The disorder is considered a milder variant of Menkes disease.

Signs and symptoms

It is characterized by a deficiency in biliary copper excretion that causes deformations in the skeleton. These include projections on the back of the skull (parasagittal bone exostoses arising from the occipital bone—the so-called "occipital horns") as well as deformities of the elbow, radial head dislocation, hammer-shaped lateral ends of the clavicles, and abnormalities of the hips and pelvis.

  • Damage to the central nervous system
  • Muscle wasting

Diagnosis

The initial diagnosis of Menkes disease (MD) and its milder variants such as Occipital Horn Syndrome is based on the clinical symptoms. Low serum copper and ceruloplasmin levels support the clinical suspicion of OHS, but biochemical confirmation in tissue culture is needed. The ultimate diagnostic proof is the demonstration of a molecular defect in ATP7A. Demonstration of the bony protuberances on the occiput will clinch the diagnosis, and these can be palpated in some patients.

Treatment

Courses of treatment for children with OHS is dependent upon the severity of their case. Children with OHS often receive physical and occupational therapy.

Prognosis

The long term natural history of OHS is not known. whereas one patient has survived to age 57. Causes of death include respiratory failure, and intracranial hemorrhage.

Research

The NIH and Cyprium Therapeutics are coordinating the joint-development of an Adeno-Associated virus gene therapy named AAV-ATP7A, for Menkes disease and its milder variants such as Occipital Horn Syndrome. In March 2017, Cyprium Therapeutics acquired the World-Wide development and commercial rights to the Menkes program at NIH/NICHD through CRADA and licensing agreements with NICHD. AAV-ATP7A is still in pre-clinical stage, although it has received orphan drug designation from the FDA.

See also

  • Cutis laxa
  • List of cutaneous conditions
  • Inborn errors of metal metabolism

References

  • GeneReviews/NCBI/NIH/UW entry on ATP7A-Related Copper Transport Disorders