Chondrodysplasia With Joint Dislocations, Gpapp Type

A number sign (#) is used with this entry because the GPAPP type of chondrodysplasia with joint dislocations is caused by homozygous mutation in the IMPAD1 gene (614010) on chromosome 8q12.

Clinical Features

Vissers et al. (2011) reported 4 individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, micrognathia, cleft palate, and facial dysmorphism. Three patients, a German girl and Turkish sisters, were from consanguineous families, and the fourth patient was born to healthy parents from Kerala, India.

Nizon et al. (2012) described 2 unrelated Turkish patients with a Catel-Manzke syndrome (616145)-like phenotype, 1 of whom was a male infant originally reported by Kiper et al. (2011), in whom they identified homozygous loss-of-function mutations in the IMPAD1 gene. The patients had severe growth retardation with short and abnormal extremities, cleft palate with micrognathia, and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Nizon et al. (2012) noted that in contrast to previously reported patients with IMPAD1 mutations who had recurrent joint dislocations, these patients had only knee hyperlaxity.

Inheritance

Kiper et al. (2011) reported a male infant, born to consanguineous Turkish parents, with classic features of Catel-Manzke syndrome (616145) as well as ligamentous laxity in the knees. Two previously born female sibs of the patient, one of whom died at birth and the other at postnatal day 13, also had features of the syndrome. Consanguinity and possibly affected sibs led the authors to suggest autosomal recessive inheritance.

Molecular Genetics

In 4 individuals from 3 unrelated families with the GPAPP form of chondrodysplasia with joint contractures, Vissers et al. (2011) identified homozygous mutations in the IMPAD1 gene (614010.0001-614010.0003). The mutations were found in heterozygous state in the parents and were not found in 1,712 control chromosomes.

In 2 unrelated Turkish patients with a Catel-Manzke syndrome (616145)-like phenotype and knee joint laxity, 1 of whom was the male infant originally reported by Kiper et al. (2011), Nizon et al. (2012) identified homozygosity for loss-of-function mutations in the IMPAD1 gene (614010.0003 and 614010.0004).