Diseases title

Occipital horn syndrome )

Orpha Number: 198
EDS IX, Ehlers-Danlos syndrome type IX, Ehlers-Danlos syndrome, type 9, X-linked cutis laxa

Occipital horn syndrome (OHS) is a mild form of Menkes disease (MD, see this term), a syndrome characterized by progressive neurodegeneration and connective tissue disorders due to a copper transport defect.Exact prevalence is unknown and approximately 20 cases have been reported to date.Onset may occur from infancy to early adulthood. Although pregnancy is usually normal, the skin may appear wrinkled and loose at birth, and umbilical or inguinal hernias may occur. Within days, hypothermia, jaundice, hypotonia, and feeding problems may develop. The first remarkable signs may be intractable diarrhea, bladder diverticulae or recurrent urinary tract infections. Motor development is delayed due to muscle hypotonia and is associated with unusual clumsiness. Height is usually normal, while mild disproportion with long trunk, narrow chest and shoulders, thoracolumbar kyphosis or scoliosis, and pectus deformity are common. The joints are hypermobile. Elbow mobility is restricted and there is a tendency toward dislocation of the elbows. Facial appearance gradually becomes distinctive. Unusual features include long, thin face, often with a high forehead, down-slanting eyes, hooked or prominent nose, long philtrum, high arched palate, and prominent large ears. The extent of skin laxity is variable and may increase with age, resulting in droopy wrinkles around the trunk. Hair is usually not conspicuously abnormal, although some patients may have dull and unusually coarse hair. Recurrence of the inguinal hernia is common. Vascular anomalies, such as varicose veins, are common, and arterial aneurysms have also been described. Intellectual capacity is low to borderline normal. Pubertal development is normal.OHS is due to mutations in the ATP7A gene (Xq21.1) encoding a copper-transport protein, Cu2+-transporting ATPase-alpha polypeptide. Patients with the milder form have a higher proportion of mutations, which lead to a partially functional protein or reduced amounts of an otherwise normal protein.Diagnosis is based on the clinical features. Radiography shows characteristic occipital horns which are symmetric exostoses protruding from the occipital bone and pointing downward. These exostoses may be found around 1-2 years of age, but are usually detected only around 5-10 years of age. They continue to grow up to early adulthood. Diagnosis is confirmed by identification of a mutation in the ATP7A gene.Menkes disease is the main differential diagnosis. Other conditions to be considered include other forms of cutis laxa and Ehlers-Danlos syndrome (see these terms).Because of the large size of the gene and the variety of the mutations observed in different families, detection of the genetic defect in a given family may take time. Therefore in at risk families it is very important to define the ATP7A mutation of the family in due time and identify the heterozygote females prior to an eventual pregnancy and prenatal diagnosis.Transmission is X-linked recessive.Treatment is mainly symptomatic. Early parenteral copper-histidine supplementation may modify disease progression, but there is no literature on this subject.Prognosis is variable in OHS, although life expectancy is substantially longer than in MD.
source: Orphanet