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Occipital Horn Syndrome (OHS)
Monday, 09 August 2004
Monday, 09 August 2004
X-linked cutis laxa
Additional entries in our database that you might find useful:   Menkes Disease (Syndrome)

What

ATP7A-related copper transport disorders are a pair of genetic diseases, Occipital Horn Syndrome (OHS) and Menkes disease, which are both caused by a mutation in a copper-transporting ATPase gene (named ATP7A). Copper is an important mineral needed for growth and development. In these diseases, copper is not properly transported to certain areas of the body thus causing a lack of proper development of these areas, such as the brain, liver and bones.

Who

OHS is generally inherited as a X-linked recessive gene; however, it is thought that about one-third of the infants affected do not have a family history of the disease. This disease generally affects only males while females may be carriers of the defective gene. X-linked recessive describes an inherited disorder in which the defective gene is on the X chromosome. Every female has two X chromosomes and every male has one X and one Y chromosome. If this X-linked recessive gene is passed on to a male child, he will have this disorder since he only has one X-chromosome. A female child will only be a carrier of this mutated gene since she has another X-chromosome that is not affected. A female will only show symptoms of a X-linked recessive disease if BOTH of her X chromosomes are defective. As a carrier, she will not show symptoms of the disease but she will be able to pass this gene on to her children. A mother who is a carrier of the gene has a 50% chance of transmitting the mutation to her children. A father who has OHS will pass it on to all of his daughters but none of his sons since he only passes on the Y chromosome to his sons. It is important for families to obtain genetic counseling if they carry this trait. Prenatal testing is a possibility if the mother is known to be a carrier.

Signs and Symptoms

Occipital horn syndrome is named based on calcifications at the base of the skull (occipital bone) that can be seen on x-ray or palpated on examination. OHS presents in early to middle childhood. Important features include:  Normal or slightly delayed intelligence  Long neck, high arched palate, long face, high forehead  Laxity (looseness) of skin and joints (“double-jointed”)  Bladder diverticula (pouches)  Inguinal hernias  Tortuous, or twisting, blood vessels  Dysautonomia (inability to regulate some parts of the nervous system), causing chronic diarrhea and orthostatic hypotension (drop in blood pressure when a person stands up suddenly)  Chronic diarrhea  Coarse, twisting hair

Possible Causes

OHS is caused by a mutation in a gene (ATP7A) that is responsible for transporting copper in and out of cells. Mutations in this gene result in a build-up of copper in some areas of the body and low amounts of copper in other areas of the body. Some areas of the body where the copper builds up include the duodenum (part of the small intestines), kidney, spleen, pancreas, and skeletal muscle. Copper is unable to be transported effectively into the brain, liver, arteries and bones. Reduced activity of copper-dependent enzymes (proteins that help with chemical reactions) are also noted with these disorders.

Diagnosis

Diagnosis is based on the clinical history and blood tests showing low amounts of copper and low amounts of ceruloplasmin (a copper containing protein). A series of complex tests on the blood (molecular genetic testing) can determine the presence of the ATP7A mutation in more than 95% of children with the disorder. Examination of the hair under the microscope shows pili torti (hair twisting 1800) and splitting of the hair. X-rays show osteoporosis (thinning and weakening of the bones), changes in the bones of the spinal column (vertebral bodies), and excess wormian bones (small bones along the sutures, or connections, between the skull bones). MRI (imaging) of the brain demonstrates a decrease in the size of the brain and twisting appearance of the blood vessels. An EEG (electroencephalogram) records the electrical activity in the brain. This may be abnormal in patients with OHS.

Treatment

Children with OHS require significant supportive care, including physical/occupational therapy. A feeding tube may need to be placed if the children are not growing well. Injections of copper histidine or copper chloride early on may improve the neurological condition slightly and may decrease the frequency of seizures, but has not been shown to increase life span. Also, the bladder obstruction or diverticula may need surgical intervention and antibiotics may be used to prevent infections and damage to the urinary system and kidneys. Current research is focusing on learning more about the disease in order to provide more effective treatments. Specifically, a study is currently looking at the benefits of using copper histidine therapy early on in the disease course.

Prognosis

The prognosis depends on the severity of the disorder. Menkes disease is generally more severe and has a worse prognosis than OHS. Children with OHS usually survive until adulthood. The use of support care is an important element in improving the outcome of children with OHS.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Justin Gorden and Menkes Syndrome Network
A wonderful family website for parents with a child with Menkes syndrome.

National Institute of Neurological Disorders and strokes   A government website of the National Institutes of Health specifically related to neurological conditions and on this link, Menkes is the primary condition. There are other links to search. Support group - Corporation for Menkes Disease 5720 Buckfield Court Fort Wayne, IN 46804 219-436-0137

Google Search for Occipital Horn Syndrome (OHS)

References and Sources

Barbagallo JS, et al (2002). “Neurocutaneous Disorders.” Dermatologic Clinics, 20:3, W.B. Saunders Company. Kaler S (2003). “ATP7A-Related Copper Transport Disorders.” www.genetests.org. University of Washington, Seattle. Author unknown (2003). “Menkes’ Disease.” In: Goetz: Textbook of Clinical Neurology, 2nd ed., Elsevier, p 659-660. Website: www.webmd.com