Dyssegmental Dysplasia, Rolland-Desbuquois Type
Description
The dyssegmental dysplasias are lethal forms of neonatal short-limbed dwarfism. Handmaker et al. (1977) coined the term 'dyssegmental dysplasia' because of the marked differences in size and shape of the vertebral bodies (anisospondyly), which he attributed to errors in segmentation. Fasanelli et al. (1985) proposed that there are different forms of dyssegmental dwarfism, a lethal Silverman-Handmaker type (224410) and a less severe Rolland-Desbuquois type. The Rolland-Desbuquois form is lethal in about 40% of patients. Although many patients survive beyond the newborn period, all exhibit neonatal distress (summary by Hennekam et al., 2010).
Clinical FeaturesGorlin and Langer (1978) analyzed cases of a form of lethal neonatal chondrodystrophy which they called dyssegmental dwarfism, or lethal anisospondylic camptomicromelic dwarfism. Affected infants are stillborn or live only a few months. Narrow chest and reduced joint mobility are constant features. Cleft palate, hydronephrosis, and hydrocephalus have been observed. In 2 cases thought to have this condition, different histology was found (Gorlin and Langer, 1978). The entity reported by Rolland et al. (1972) was probably the same as that in the case reported by Dinno et al. (1976) and in the 3 cases reported by Langer et al. (1976).
Aleck et al. (1987) presented further evidence for the existence of at least 2 forms of dyssegmental dysplasia, both autosomal recessive, which can be delineated on clinical, radiographic, and morphologic grounds. A lethal form, the Silverman-Handmaker type, is characterized by stillbirth or neonatal death and by distinct and more severe radiographic changes. In the less severe, Rolland-Desbuquois form, survival beyond the newborn period is frequent and the radiographic changes resemble Kniest dysplasia (156550).
Svejcar (1983) quoted R. J. Gorlin (Minneapolis) as suggesting that dyssegmental dwarfism was present in a case included in one of the first applications of roentgenology to the diagnosis of congenital malformations (Simmonds, 1900). Svejcar (1983) found abnormal gel electrophoretic patterns of collagen peptides, pointing to a deficiency in alpha-1 chains. This deficiency may be responsible for increased crosslinking and the observed alterations in extractability of collagen. Svejcar (1983) observed 2 cases, 1 in the offspring of presumably unrelated Jordanian-Palestinians and 1 in the offspring of unrelated Turkish parents. Hypertrichosis was found in both cases. The limbs were short and bent with reduced mobility.
Maroteaux et al. (1996) described 2 patients with a disorder related to but probably distinct from dyssegmental dysplasia. Skeletal manifestations included severe micromelia, dolichocephaly, flat face, and cleft palate. The hands appeared normal. X-rays revealed short, broad long bones with flared metaphyses, delayed epiphyseal ossification, and flat vertebral bodies. Coronal lumbar cleft was also observed. Mutations of COL2A1 were sought, but none was found. Distinguishing the phenotype from dyssegmental dysplasia was a severe glaucoma resulting in exophthalmos and corneal opacities.
Prabhu et al. (1998) reported the case of a male infant born with clinical and radiographic evidence of a lethal form of dyssegmental dysplasia most compatible with the Silverman-Handmaker type. Unusual was survival of the infant for more than 8 months. He had ocular and central nervous system abnormalities that had not been described previously. His clinical course included significant feeding and respiratory difficulties, severe physical and psychomotor retardation, and recurrent fever possibly of central origin. The parents were first cousins of Druze-Lebanese origin, supporting an autosomal recessive mode of inheritance.
InheritanceGorlin and Langer (1978) stated that affected sibs and parental consanguinity support autosomal recessive inheritance of dyssegmental dwarfism.