Pseudodiastrophic Dysplasia
Description
Pseudodiastrophic dysplasia is characterized by short-limbed short stature at birth, facial dysmorphism (hypertelorism, flat nose, prominent cheeks, micrognathia), cleft palate, and a distinctive skeletal phenotype including narrow thorax, scoliosis, rhizomelia, ulnar deviation of the wrist, proximal interphalangeal joint dislocation, dislocation of large joints, particularly of the elbows, and talipes equinovarus (summary by Yap et al., 2016).
Clinical FeaturesPseudodiastrophic dysplasia was first described in 2 infant sisters by Burgio et al. (1974). Although the disorder showed similarities to diastrophic dysplasia (222600), specifically, rhizomelic shortening of the limbs and severe clubfoot deformity, other radiologic and chondroosseous features were different. Both sisters died suddenly of unexplained hyperthermia, the first at age 8 months and the second at 4 days.
Canki et al. (1979) reported a female with pseudodiastrophic dysplasia who died at 1 month of age. Features distinct from diastrophic dysplasia included proximal phalangeal joint dislocations and platyspondyly.
Eteson et al. (1986) reported 4 unrelated patients, 2 males and 2 females, with pseudodiastrophic dysplasia. All had elbow dislocations, scoliosis, and clubfoot. Two survived infancy and were older than 4 years of age. Odontoid hypoplasia with C1-C2 dislocation on flexion was demonstrated radiographically in 1 patient. Cystic enlargement of the pinnae does not occur in pseudodiastrophic dysplasia. The clubfoot of pseudodiastrophic dysplasia responds better to physical and surgical therapy than does that of diastrophic dysplasia. The distinct morphologic abnormality of the growth plate in diastrophic dysplasia consists of an irregular distribution of degenerating chondrocytes in the resting cartilage, with focal areas of aggregated collagen fibrils and large cystic areas containing fibrovascular tissue, resulting in intracartilaginous ossification. This histologic appearance has not been observed in pseudodiastrophic dysplasia.
Canki-Klain et al. (1990) described 2 further cases. They pointed out that in pseudodiastrophic dysplasia platyspondyly is more pronounced than in diastrophic dysplasia and there is often marked lumbar lordosis. The vertebral bodies in the lumbar region show tongue-like deformities. The cranium shows an enlarged bitemporal diameter with midface hypoplasia. The hands are quite different with characteristic multiple interphalangeal and metacarpophalangeal joint dislocations with normal appearance of the first metacarpal in pseudodiastrophic dysplasia, and 'hitchhiker thumb' (abduction of the hypermobile and proximally inserted thumb) in diastrophic dysplasia. Cystic swelling of the pinnae appearing between the first day and the twelfth week of life in diastrophic dysplasia was never seen in pseudodiastrophic dysplasia. Several of the patients with pseudodiastrophic dysplasia died unexpectedly as neonates or infants. Canki-Klain et al. (1990) referred to a second unpublished observation of 2 affected sisters born to unrelated parents from Sicily. Three unrelated probands reported by the Maroteaux group (Canki-Klain et al., 1990) were all born to parents who originated from a mountainous, relatively closed region of Slovenia. Growth cartilage histology is said to be quite different in diastrophic dysplasia and pseudodiastrophic dysplasia.
Diastrophic dysplasia was shown by Hastbacka et al. (1994) to be the result of a defect in the sulfate transporter gene DTDST that encodes a widely distributed, sulfate/chloride antiporter of the cell membrane. Further studies showed that 2 other chondrodysplasias, atelosteogenesis type 2 (256050) and achondrogenesis type 1B (600972) are caused by mutations in the same sulfate transporter. Cetta et al. (1997) demonstrated that a patient with pseudodiastrophic dysplasia had no defect in the DTDST gene. Sulfate uptake by skin fibroblasts was normal, indicating normal sulfate transport. Sulfation of proteoglycans was also normal. No abnormality of the DTDST gene was demonstrated by SSCP screening.
Fischetto et al. (1997) reported a female newborn with pseudodiastrophic dysplasia. In addition to typical features of the disorder, she had omphalocele and a complex heart defect involving the septal and mitral valve. She died of cardiopulmonary failure at age 4 months.
Yap et al. (2016) reported the findings in 2 fetuses with pseudodiastrophic dysplasia whose healthy, unrelated Caucasian parents had 2 healthy sons. One fetus died in utero at 16 weeks' gestation. Postmortem examination showed marked nuchal edema and significant shortening and bowing of all long bones, more marked in the radii, ulnae and femora. The sacrum was small with absent ossification of the pubic bones. There was platyspondyly and reduced ossification of the cervical vertebral segments. The ribs were short, but of normal morphology, and there were genitourinary anomalies. Serial ultrasound scans in the second fetus between 22 and 35 weeks' gestation showed persistent severe subcutaneous edema of neck and thorax. Long bones were below the 2nd centile with distal bones more severely shortened. Bowing had ameliorated by 22 weeks' gestation. The facial profile showed flat midface and protuberant eyes. Polyhydramnios had developed, and labor was induced. The child showed typical features of the disorder and died at age 6 months.
InheritanceThe occurrence of pseudodiastrophic dysplasia in sibs of unaffected parents by Burgio et al. (1974) and Yap et al. (2016) supports autosomal recessive inheritance.