Parastremmatic Dwarfism

A number sign (#) is used with this entry because of evidence that parastremmatic dwarfism is caused by heterozygous mutation in the TRPV4 gene (605427).

Clinical Features

Langer et al. (1970) described 3 patients with a form of dwarfism in which deformities are recognized in the first 6 to 12 months of life. They named the disorder parastremmatic from the Greek term for twisted. Clinically the full syndrome is manifested by 10 years. Adult height is 90 to 110 cm. There are bizarre and symmetric deformities of the legs with severe genu valgum, bowing of the long bones, twisted thighs and shanks along the long axis, short neck, kyphoscoliosis, multiple contractures of major joints, clear cornea and normal cardiovascular system. Intelligence is also normal and there is no abnormal mucopolysacchariduria. Radiographs show very coarse trabeculations with areas of irregular, dense stippling and streaking producing a 'flocky or woolly' appearance. In the pelvis this is seen as a lace-like border of the iliac crests. The metaphyses are clear and contain 'flocky' bone; severely deformed and radiolucent epiphyses are present. The evidence for dominant inheritance comes from the report of father and daughter by Rask (1963). Since the daughter was as severely affected as the father, the causative gene is probably autosomal.

Sensenbrenner et al. (1974) reported a 24-year-old woman who displayed many of the features of the parastremmatic form of dwarfism. On radiography, the characteristic flaky appearance of areas of endochondral bone was seen only in some of the vertebrae, the proximal femur, and possibly near the deltoid tuberosities; bone density was noted to be surprisingly good in the limbs.

Nishimura et al. (2010) examined a 7-year-old girl with short stature who had a marked 'windswept' deformity of the legs combined with flexion at the knee joint. Fingers and toes were long, and she had platyspondyly with thoracolumbar scoliosis and diffuse metaphyseal changes. Hand x-rays showed no brachydactyly, but carpal maturation appeared retarded. Both the distal femoral metaphyses and the proximal tibial metaphyses had a flaky appearance consistent with diffuse enchondromatosis. Nishimura et al. (2010) stated that the features of this patient fit well with parastremmatic dysplasia, and noted that her phenotype was similar to that of the patient described by Sensenbrenner et al. (1974). In addition, because the spine changes in parastremmatic dysplasia are similar to those seen in metatropic dysplasia (156530), Nishimura et al. (2010) suggested that the former might be a variant of the latter.

Molecular Genetics

In a 7-year-old girl with parastremmatic dwarfism, Nishimura et al. (2010) analyzed the candidate gene TRPV4 and identified heterozygosity for a missense mutation (R594H; 605427.0003) that had previously been found in patients with the Kozlowski type of spondylometaphyseal dysplasia (184252).