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KEY POINTS
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Key Points

  • Chondrodysplasia punctata comprises a group of genetically heterogenous skeletal dysplasias characterized by small calcified densities in the epiphyses of the long bones.

  • The rhizomelic form (RCDP) is more severe and inherited as an autosomal recessive condition. Rhizomelic chondrodysplasia punctata is a disorder of the peroxisomes.

  • The nonrhizomelic form, also known as Conradi–Hünermann syndrome, can be inherited as an autosomal dominant, X-linked recessive or dominant condition. It is generally milder.

  • Sonographic findings include profound humeral and femoral shortening in rhizomelic chondrodysplasia punctata. Multiple hyperechoic foci (puncta), nasal hypoplasia, midface depression, vertebral anomalies, and congenital heart defects are associated with both RCDP and Conradi–Hünermann syndrome.

  • Differential diagnosis includes skeletal dysplasias, autosomal trisomies, Zellweger syndrome, disorders of vitamin K metabolism, warfarin exposure, Smith–Lemli–Opitz syndrome, and GM1gangliosidosis.

  • Pregnant women carrying fetuses with punctate calcifications should be referred to a tertiary center and to a medical geneticist. Chromosome analysis is indicated to rule out trisomy and deletions of Xp22.3.

  • There are three types of RCDP; type 1 is most common, caused by mutations in PEX7. Molecular diagnosis is possible for all three types.

  • Prognosis is poor for RCDP. Only 50% of affected infants survive past the age of 6 years. All affected infants have severe failure to thrive, mental retardation, joint contractures, and cataracts.

  • Infants affected with Conradi–Hünermann syndrome have milder symptoms, generally normal intelligence and, with the exception of the X-linked dominant form in males, a fairly normal lifespan.

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CONDITION
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Chondrodysplasia punctata denotes a group of skeletal dysplasias characterized by locally disordered bone mineralization that results in bone stippling observed on radiographs obtained during the newborn period (Pryde et al., 1993). The areas of punctate calcification were first described by Conradi in 1914. In 1931, Hünermann designated the disorder “chon-drodystrophia calcificans congenita.” This term was defined as the X-ray finding of small calcified densities in the epiphyses (Hyndman et al., 1976). The disorder recognized by Hünermann also included micromelia, a saddle nose deformity, flexion contractures, cataracts, and a dermopathy. As used today, the term chondrodysplasia punctata comprises a group of genetically heterogeneous disorders (Spranger et al., 1971). Some of these are associated with rhizomelia (proximal limb shortness) and some are not. The rhizomelic form is generally more severe. It has been subdivided into three types, each of which is associated with a mutation in a different gene (see Figure 99-1). All three types are inherited as autosomal recessive conditions. The nonrhizomelic form of chondrodysplasia punctata, also known as Conradi–Hünermann syndrome, is milder and can be inherited as an autosomal dominant, X-linked recessive, or X-linked dominant condition. A rarer form of mild chondrodysplasia punctata, known as the tibia-metacarpal type, is inherited as an autosomal dominant condition.

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Figure 99-1

Approach to the diagnosis of the conditions characterized by small calcified densities in the epiphyses of the long bones.

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