Clinical manifestations in ASPED are not only restricted to the hands, and the original description reported various combinations of angel-shaped middle phalanges, hip dysplasia and dental anomalies (hypodontia). Patient stature ranges from short to normal. Hip dysplasia gives rise to premature or severe osteoarthritis causing severe intermittent hip pain. Non-specific brachydactyly and hyperextensible interphalangeal joints have been reported, as well as delayed bone age. Delayed dentition, abnormally placed teeth, premature loss of teeth, abnormal enamel, and malocclusion have also been described in some.
ASPED is caused by mutations in the growth differentiation factor 5 (GDF5) gene, located on chromosome 20q11.2, encoding CDMP1 (cartilage derived morphogenetic protein). CDMP1 belongs to the TGF beta super family and plays a role in bone growth and joint morphogenesis.
