Diastrophic dysplasia is a distinct clinical entity characterized by disproportionate short stature, cleft palate, clubfoot, progressive scoliosis, limited joint mobility, proximally placed first metacarpals (“hitch-hiker’s thumb”), and cystic degeneration of the pinnae of the ear (“cauliflower deformity”) (Figure 93-1) (Lachman et al., 1981). This condition was first described by Lamy and Maroteaux (1960), who used the Greek word diastrophos, meaning twisted, to describe the prominent involvement of the feet and spine in this type of dwarfism (Diab et al., 1994).

Diastrophic dysplasia exhibits distinctive histopathology, which consists of cytoplasmic accumulation of glycogen and fat in the chondrocytes, resulting in variability of chondrocyte size, shape, and viability (Diab et al., 1994). There is nonuniformity of the cartilage matrix with fibroblast and vascular ingrowth, resulting in fibrotic foci and areas of intracartilaginous calcification (Diab et al., 1994). The abnormalities of the cartilage matrix are considered pathognomonic and are visible with light microscopy. The underlying problem is an excessive amount of collagen deposition within the cartilage matrix rather than a lack of collagen. The excessive deposition of structurally abnormal collagen occurs predominantly in the growth cartilage rather than the resting carti-lage (Shapiro, 1992). This cartilage abnormality affects the entire epiphyseal area, which leads not only to shortening of the long bones, but also to extreme malformation of the epiphyseal ends of the bones. This abnormality affects the articular surfaces, causing precocious osteoarthritis (Shapiro, 1992).

The underlying genetic basis of diastrophic dysplasia is the result of a mutation in a novel sulfate transporter gene, known as the diastrophic dysplasia sulfate transporter (DTDST) and also, more recently, as SLC26A2 (Hästbacka et al., 1994, 1996). Impaired function of this gene product leads to undersulfation of proteoglycans in cartilage matrix, which leads to abnormal cartilage formation and results in the disease phenotype (Hästbacka et al., 1994).

Diastrophic dysplasia has been observed only in whites. To date, more than 300 patients with diastrophic dysplasia have been described, and interestingly, the majority of them are in Finland (Ryoppy et al., 1992), where the gene for diastrophic dysplasia is unusually common due to an apparent founder effect in this relatively genetically isolated population (Hästbacka et al., 1994). The incidence of diastrophic dysplasia is 1 in 32,600 livebirths in Finland, where it is the most common skeletal dysplasia (Poussa et al., 1991). The carrier frequency is 1 in 90 individuals there.

Because of the rarity of this condition in the non-Finnish population, relatively few reports of the prenatal sonographic diagnosis of diastrophic dysplasia exist in the literature (Mantagos et al., 1981; Kaitila et al., 1983; Jung et al., 1998; Tongsong et al., 2002; Wax et al., 2003). The earliest prenatal diagnosis of this condition was made at 13 weeks using transvaginal sonography (Severi et al., 2003). The prenatal diagnosis of diastrophic dysplasia was first described in 1980, when O’Brien et al. (1980) reported the diagnosis in a family with a previous affected child. Prenatal sonography was performed at 13 weeks 5 days of menstrual age, and revealed a crown-to-rump length of 43 mm, which corresponded to a gestational age of 11 weeks. The study was repeated at 16 weeks of gestation, when the femur length measured 13 mm (normal for gestational age: 19-26 mm). Thus, long bone shortening was retrospectively demonstrated in this condition during the early second trimester (13 weeks 5 days). In this report, fetoscopy demonstrated extremely short and curved limbs in the affected fetus. Examination of the face and oral cavity also showed micrognathia and cleft palate, other findings that are typically seen in diastrophic dysplasia. In another case, also complicated by a positive family history, prenatal sonography performed at 16 weeks of gestation demonstrated abnormally short limbs (less than 3 SD below the mean for gestational age) and lateral projection of the thumbs (Figure 93-2). These findings revealed an affected fetus. These authors recommended assessing fetuses at risk with serial examinations at 16, 20, 24, and 32 weeks of gestation because they were concerned that normal findings at 16 weeks might still be consistent with a diagnosis of an affected infant (Gollop and Eigier, 1987). In another affected case with no family history of diastrophic dysplasia, ultrasound examination performed at 31 weeks revealed severe micromelia (all long bones less than 2 SD below the mean for gestational age), normal amniotic fluid, ulnar deviation of the hands, abducted and proximallyinserted thumbs and great toes, bilateral clubfeet, apparent elbow and knee joint contractures, cervical kyphosis (Figure 93-3), and micrognathia. The diagnosis of diastrophic dysplasia was confirmed postnatally (Gembruch et al., 1988).

Other sonographic findings in diastrophic dysplasia include normal skull and vertebral body ossification and occasional scoliosis. In a summary of 18 at-risk pregnancies in Finland, prenatal sonography performed during the second trimester was highly accurate in the diagnosis of this condition (Hästbacka et al., 1993). Of the 18 fetuses at risk, 5 were predicted to be affected and 13 were predicted to be unaffected by long bone measurements. All diagnoses were confirmed by postnatal or post-termination assessment.

More recently, three-dimensional ultrasound studies were compared to two-dimensional studies in a case of diastrophic dysplasia (Sepulveda et al., 2004). The three-dimensional study provided clearer views of the limb anomalies and the facial micrognathia.

The differential diagnosis includes campomelic dysplasia, osteogenesis imperfecta, thanatophoric dysplasia, Kniest dysplasia, and chondrodysplasia punctata.

Other conditions to be considered within the differential diagnosis include pseudodiastrophic dysplasia and atelosteogenesis type II. In pseudodiastrophic dysplasia, patients exhibit a large cranium with midface hypoplasia, long clavicles, short limbs, and platyspondyly (Eteson et al., 1986), but the cauliflower ear characteristic of diastrophic dysplasia does not occur in this condition. The distinguishing features of pseudodiastrophic dysplasia include elbow and proximal interphalangeal joint dislocation and progressive scoliosis in infancy. Joint abnormalities seen in pseudodiastrophic dysplasia respond well to physical therapy. This is not true for diastrophic dysplasia. Pathologically, the two conditions are quite different. In pseudodiastrophic dysplasia the resting cartilage is normal, with no areas of fibrous degeneration in the cartilage matrix of these patients.

In atelosteogenesis type II, patients exhibit marked shortness of limbs with metaphyseal widening, a characteristic bifid humerus, cervical scoliosis, and abnormalities of the digits. Radiographs reveal more severe abnormalities of the tubular bones of the hands and feet as compared with diastrophic dysplasia (Qureshi et al., 1995). On the other hand, the histologic abnormalities of the resting cartilage in atelosteogenesis type II are similar to those seen in diastrophic dysplasia. This is not surprising, as atelosteogenesis type II is caused by mutations in the same gene that causes diastrophic dysplasia, DTDST (Hästbacka et al., 1996).