Occipital Horn Syndrome (OHS) is a rare, inherited disorder that affects the body’s connective tissues. It is also known as Ehlers-Danlos syndrome, type IX, and is a milder variant of the related condition Menkes disease. The syndrome involves a wide range of signs that differ in severity, stemming from an underlying issue with copper metabolism. The condition becomes apparent from infancy to childhood and is characterized by skeletal abnormalities and issues with the skin, joints, and internal organs.
Genetic Origins and Copper Metabolism
Occipital Horn Syndrome is caused by mutations in the ATP7A gene. This gene holds the instructions for producing a protein that transports copper across cell membranes. Proper copper distribution is necessary for the function of many enzymes involved in bone, skin, hair, blood vessel, and nervous system health. The mutations found in OHS do not eliminate the protein’s function entirely but reduce its efficiency, leading to a maldistribution of copper.
This condition is inherited in an X-linked recessive pattern, which explains why it predominantly affects males. Males have one X chromosome, so a single mutated copy of the ATP7A gene is enough to cause the disorder. Females have two X chromosomes, so a mutation on one is usually compensated for by the normal copy on the other, making them carriers who typically do not show symptoms. While many cases are inherited, about one-third of instances arise from spontaneous mutations where there is no family history.
The impaired copper transport leads to a paradoxical situation: copper accumulates in some tissues, like the intestine and kidneys, while it is deficient in others, such as the brain, bones, and arteries. This functional deficiency causes the syndrome’s characteristic features. The activity of copper-dependent enzymes is compromised, affecting processes like collagen synthesis, which is needed for healthy connective tissue.
Key Signs and Symptoms
A defining feature of OHS is the presence of wedge-shaped calcium deposits on the occipital bone. These “occipital horns” are not always palpable but are clearly visible on skull X-rays. Other skeletal issues include:
- Hammer-shaped clavicles
- Scoliosis
- Dislocations of the radial head near the elbow
- Bowing of long bones
- Unusual shaping of the pelvic bones
Individuals often have soft, loose, and hyperextensible skin, a condition known as cutis laxa. This can result in a wrinkled appearance, especially on the hands and belly. Joint hypermobility is also a frequent finding, which can contribute to clumsiness and delayed motor development in some children.
Bladder diverticula, which are pouches that form in the wall of the bladder, are a common issue. Vascular problems are also a concern, with arteries, particularly those in the brain, often being twisted and elongated (tortuous). This tortuosity can increase the risk for aneurysm formation. Unlike the severe neurological deterioration seen in Menkes disease, intelligence in individuals with OHS is in the normal to borderline range. Many also experience chronic diarrhea and issues with autonomic nerve function, such as postural orthostatic hypotension.
The Diagnostic Process
Diagnosis of Occipital Horn Syndrome begins with a clinical evaluation. A physician assesses for physical signs, such as loose skin, overly flexible joints, coarse hair, and hernias. These symptoms, especially in a male patient, raise suspicion of a copper metabolism disorder. A family health history is also gathered to determine if there is a pattern of X-linked inheritance.
Radiological imaging is a key part of the diagnostic process. An X-ray of the skull is performed to look for the eponymous occipital horns, which are a hallmark of the syndrome. Other skeletal surveys may identify additional bone abnormalities, such as deformities in the clavicles or long bones.
Biochemical tests on blood samples measure the levels of copper and ceruloplasmin, a protein that carries copper in the blood. In OHS, these levels are low, which helps differentiate OHS from other connective tissue disorders.
A definitive diagnosis is made with molecular genetic testing. This DNA analysis identifies a specific mutation in the ATP7A gene. Confirming the mutation establishes the diagnosis and allows for accurate genetic counseling for the family regarding risks for future pregnancies.
Approaches to Management and Care
There is no cure for Occipital Horn Syndrome, so treatment focuses on managing specific symptoms and improving quality of life. Care requires a multidisciplinary team of specialists to address the various ways the disorder can manifest.
Surgical interventions may be needed for structural problems. The repair of inguinal or umbilical hernias is common to prevent complications like bowel obstruction. Surgery may be required to correct bladder diverticula if they cause urinary issues. Regular monitoring of the vascular system is important to watch for the development of aneurysms.
Physical and occupational therapy play a large part in daily management. Therapists work with patients to manage joint instability, improve muscle tone, and enhance motor skills affected by hypermobility and hypotonia. For those with autonomic dysfunction, medications like droxidopa may be used to manage symptoms such as low blood pressure.
Genetic counseling is recommended for affected individuals and their families. Genetic counselors provide information about the X-linked inheritance pattern, the likelihood of passing the condition to future generations, and options for prenatal and carrier testing. While copper injections are used in Menkes disease, they have not been shown to be effective for the connective tissue problems in OHS.