OMIM ID:
Arthrogryposis, Perthes Disease, and Upward Gaze Palsy
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Upward gaze is restricted and attempts to do so are associated with exotropia.
Systemic Features
Arthrogryposis with restricted joint mobility is present in both proximal and distal joints, including hips, elbows, hands, and knees. It is usually evident early in infancy when parents note “tight joints”. Other joint deformities present to some degree are “trigger finger” deformities found in the middle fingers and thumbs. Hip pain and difficulty walking as early as 3 years of age can be signs of avascular necrosis of the femoral head (Perthes disease).
Pyloric stenosis can lead to severe, recurrent vomiting. Pulmonic stenosis is commonly present and there are often cardiac septal defects as well as valvular malfunctions. Bronchial asthma is a feature.
Genetics
Inheritance
One extended consanguineous Saudi family with three affected females has been reported. No similar findings are present in the parents and the condition is most likely transmitted as an autosomal recessive. A homozygous mutation in NEK9 (14q24) has been associated with this condition.
Heterozygous mutations in the same gene have been identified in 3 patients with nevus comedonicus (617025).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.