Craniometadiaphyseal Dysplasia

Description

Craniometadiaphyseal dysplasia (CRMDD) is characterized clinically by macrocephaly with frontal prominence, dental hypoplasia, and increased bone fragility. Diagnostic radiologic features include thin bones in the superior part of calvaria with prominent wormian bones, diaphyseal widening of the long tubular bones in early childhood with wide undermineralized metaphyses in older individuals, widened ribs and clavicles, and broadening of short tubular bones with increased transparency and thin cortices (summary by Dhar et al., 2010).

Clinical Features

The first case of craniometadiaphyseal dysplasia was reported by Schwarz (1960) as an example of craniometaphyseal dysplasia in an 18-year-old girl who was short, with frontal bossing, prominent mandible, and dental caries. She had a history of multiple fractures, severe scoliosis, bowing of the lower limbs, bilateral cubitus valgus with dislocated radial heads, coxa valga deformity, and deformities of the chest, pelvis, and elbows.

Williams et al. (1989) and Langer et al. (1991) described the same brother and sister, born to clinically normal, first-cousin parents of Polish ancestry, who presented with a large head, prominent forehead, delayed closure of a large anterior fontanel, mild downward slant of palpebral fissures, malar hypoplasia, high-arched palate, and hypoplastic teeth; characteristic skull changes including multiple wormian bones; wide long tubular bones without normal metaphyseal flaring; wide short tubular bones without normal diaphyseal constriction and sometimes with actual diaphyseal expansion; and wide ribs and clavicles. Langer et al. (1991) called this condition craniometadiaphyseal dysplasia, wormian bone type, and distinguished it from craniometaphyseal dysplasia (see CMDR, 218400). Although after infancy, the long tubular bones appear the same in both disorders, the skull changes of CRMDD, e.g., thin bone in the superior part of the calvaria and prominent wormian bones, are not present in CMDR. The short tubular bones are strikingly different in the 2 disorders. In infants with CMDR, the diaphyses of the long tubular bones are sclerotic, but the modeling is normal.

Santolaya et al. (1998) described a 4-year-old Moroccan boy, the first child of first-cousin parents, with craniometadiaphyseal dysplasia, wormian bone type. The patient had a large head with prominent forehead, skull changes showing multiple wormian bones, wide long tubular bones without the usual metaphyseal flare, wide short tubular bones without the normal diaphyseal constriction, and wide ribs and clavicles.

Dhar et al. (2010) provided a 25-year follow-up of the brother reported at the age of 8 years by Williams et al. (1989) and reviewed other reported cases. They recommended that patients with this condition get evaluated with bone density scans and hearing and ophthalmologic examinations on a regular basis because nerve impingement secondary to progressive bone deformities can be a problem.

Inheritance

Parental consanguinity in the families with craniometadiaphyseal dysplasia reported by Langer et al. (1991) and Santolaya et al. (1998) is consistent with autosomal recessive inheritance.

History

Gorlin et al. (1969) had suggested that the patient reported by Schwarz (1960) as an example of craniometaphyseal dysplasia and the patient reported by Lelek (1961) as an example of Camurati-Engelmann disease had the same distinct disorder. They proposed the designation Schwarz-Lelek syndrome. However, Hennekam et al. (2010) suggested that the patient reported by Lelek (1961) had craniometaphyseal dysplasia (see 122860).