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KEY POINTS
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Key Points

  • Second most common lethal short-limb dysplasia.

  • Incidence is 1/40,000 to 1/50,000 livebirths.

  • Characterized by severe micromelia, lack of vertebral ossification, and a large head with relatively normal ossification of the calvarium; also associated with polyhydramnios, cystic hygroma, and hydrops fetalis.

  • Type I (20% of cases) is more severe and is inherited as an autosomal recessive. Type IB is caused by a mutation in the diastrophic dysplasia sulfate transporter (DTDST) gene.

  • Type II (80% of cases) is caused by mutations in the COL2A1 gene, which results in significantly decreased type II collagen. Type II is usually a de novo dominant mutation, with rare reports of recurrence due to germline mosaicism.

  • Increased incidence of prematurity and stillbirth. Condition is lethal in perinatal period.

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CONDITION
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The term achondrogenesis refers to a diverse group of generally lethal chondrodysplasias characterized by a short trunk, severe micromelia, and a disproportionately large cranium. Achondrogenesis is the second most common lethal short-limb dysplasia. The term achondrogenesis is actually a misnomer, as it implies that cartilage is not made. In this condition, cartilage is made but it is profoundly abnormal. A more correct term would be chondrogenesis imperfecta (Eyre et al., 1986).

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Subclassification of the different conditions included under the term achondrogenesis has been confusing. Historically, two types of achondrogenesis have been described: type I is referred to in the literature as Parenti–Fraccaro syndrome. This subtype accounts for 20% of cases and is the more severe of the two. Type II achondrogenesis—termed Langer–Saldino syndrome—accounts for 80% of cases. In 1983, Whitley and Gorlin reviewed 79 cases that presented with a lethal neonatal chondrodysplasia. Affected infants had a short trunk, extreme micromelia, and a disproportionately large cranium. Radio-graphically, they were demonstrated as having deficient spine ossification, short ribs with cupped and flared ends, and absent pubic and ischial ossification. On the basis of this study, they identified four subtypes. These included type I (Parenti–Fraccaro), which was characterized by multiple rib fractures and the most marked limb shortening. Within the type II category (Langer–Saldino), they identified three subtypes, characterized by differences in the severity of the micromelia and ossification of the vertebrae. Although type I achondrogenesis was traditionally called Parenti–Fraccaro syndrome, a review by Borochowitz et al. (1988) revealed that the original case described by Parenti had a well-ossified skull and ossification of the vertebral bodies. This original case, therefore, was more likely to represent a more mildly affected case of achondrogenesis type II.

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Borochowitz et al. (1988) attempted to more accurately classify the subtypes of achondrogenesis (Figure 97-1). In this report, they divided achondrogenesis into three subtypes: the most severely affected is lethal achondrogenesis, type IA (Houston–Harris). This condition is characterized by a poorly ossified skull, multiple rib fractures, and a completely unossified spine (Figure 97-2). Type I also includes lethal achondrogenesis, type IB (Fraccaro), which follows the original case ...

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