Alkuraya (2011) reported a consanguineous Saudi family in which 2 sisters and a female cousin had a similar disorder characterized by arthrogryposis apparent sin...
Alkuraya (2011) reported a consanguineous Saudi family in which 2 sisters and a female cousin had a similar disorder characterized by arthrogryposis apparent since early childhood, avascular necrosis of the hip (Perthes disease), and upward gaze palsy. Limited hip abduction was noted in infancy, and they had multiple joint contractures involving the hands, elbows, hips, and knees. Two had camptodactyly of the fingers and 1 had overriding toes. Perthes disease was diagnosed in 2 in early childhood (ages 2 to 3 years), and the third patient had mild collapse of the medial aspect of both femoral heads. Upward gaze palsy became apparent later in childhood in all 3, with an otherwise normal neurologic exam. All girls also had bronchial asthma, and 1 had atopic dermatitis. Additional features included pyloric stenosis in 2, pulmonic stenosis in 2, and a ventricular septal defect and small atrial septal defect in 1 each. Development was normal, although 1 girl had mildly decreased IQ that may have been attributable to birth hypoxia.
The transmission pattern of APUG in the family reported by Alkuraya (2011) was consistent with autosomal recessive inheritance.
▼ Molecular Genetics
In 31 multiplex consanguineous families that appeared to have novel dysmorphology syndromes, including the Saudi family originally described by Alkuraya (2011), Shaheen et al. (2016) performed autozygome analysis followed by whole-exome and whole-genome sequencing. In the Saudi family with APUG, they identified homozygosity for a missense mutation in the NEK9 gene (R681H; 609798.0002) that segregated with disease.