Kyphomelic Dysplasia

Clinical Features

Hall and Spranger (1979) described 2 brothers with congenital bowing and short broad bones. The proximal part of the limbs were most severely affected, particularly the femurs. In early infancy the metaphyses were moderately flared and irregular, but improved dramatically during childhood. The ribs were also short, resulting in narrow chest and pigeon breast. Peripheral joints showed some limitation in range of motion. Mental development was normal. Disproportionate short stature was a persistent feature. Possible identity to 2 male cases reported by Khajavi et al. (1976) as 'short-limbed campomelic syndrome, normocephalic type' was suggested.

Rezza et al. (1984) described a brother and sister with kyphomelic dysplasia, and Turnpenny et al. (1990) described affected male sibs.

Temple et al. (1989) described a case with associated cleft lip and palate. They emphasized the good prognosis for motor and intellectual development. This disorder is distinguished from campomelic dysplasia (114290) by the predominance of tibial bowing, hypoplastic scapulas, mental retardation, and sex reversal in some affected females in the latter condition.

O'Reilly and Hall (1994) provided a 6-year follow-up of one of the patients described by Temple et al. (1989). They indicated that 11 cases of kyphomelic dysplasia had been reported. The patient they described in detail was a boy who at the age of 3 years and 3 months had rhizomelic shortening of the limbs with anterior bowing of the thighs, still evident but improved since infancy. A radiograph showed flattening and fragmentation of the right capital femoral epiphysis consistent with Perthes disease (150600). At the age of 6 years he was found to have bilateral changes of avascular necrosis of the capital femoral epiphysis. Other studies showed a hydronephrotic right kidney caused by obstruction at the level of the vesicoureteric junction. O'Reilly and Hall (1994) suggested that abnormal gait with stress injury to the capital epiphysis had resulted in avascular necrosis and that other syndromes with severe bowing of the femurs may be associated with Perthes disease.

Corder et al. (1995) described an infant with this disorder who also had profound humeral and cellular immunologic abnormalities consistent with severe combined immunodeficiency (SCID; see, e.g., 601457). The infant died at age 2 months of overwhelming cytomegalovirus pneumonia.

Corder et al. (1995) pointed out that 10 of 11 patients, including their own, were male. They suggested the possibility of X-linked recessive inheritance.

Diagnosis

Prasad et al. (2000) stated that about 15 cases of kyphomelic dysplasia had been reported. They presented the clinical, radiologic, and pathologic findings of an antenatally detected female fetus with this disorder. X-rays showed curved humeri, radii, ulnae, and femora, with straight tibiae and fibulae. The authors provided a tabulation of 13 other skeletal dysplasias with bent bones and contrasted the clinical and genetic features.

Pryde et al. (2003) reported a rare prenatal ultrasound finding of severe localized and symmetric bowing of the femurs in the absence of other significant skeletal or nonskeletal abnormalities. A provisional diagnosis of kyphomelic dysplasia was made. The authors noted that kyphomelic dysplasia, in contrast to campomelic dysplasia, principally involves the femurs, with relative sparing of the remainder of the skeleton, and can be difficult to distinguish from symmetric cases of femoral hypoplasia-unusual facies syndrome (134780).

Le Merrer et al. (2003) reviewed the confusing category of bent-bone chondrodysplasias. They suggested that severe (neonatal) cases of cartilage-hair hypoplasia (CHH; 250250) may be mistakenly diagnosed as kyphomelic dysplasia.

Kuijpers et al. (2003) described a female patient with an initial diagnosis of kyphomelic dysplasia in whom clinical and radiologic features reported up to the age of 8 years gradually changed and became more typical for CHH. The diagnosis of CHH was confirmed by the finding of compound heterozygosity for 2 novel mutations in the RMRP gene (see 157660.0016).

Maclean et al. (1983) reported a boy with broad, short, and severely angulated femurs as the salient feature of a generalized skeletal dysplasia which they diagnosed as kyphomelic dysplasia. Other findings included milder bowing of other long bones, narrow thorax, platyspondyly, micrognathia, and skin dimples. Spranger et al. (2000) reclassified this patient as having Schwartz-Jampel syndrome (SJS1; 255800) because as the patient got older, blepharophimosis and ptosis had worsened. They suggested that kyphomelic dysplasia does not exist as a nosologic entity.