Diastrophic dysplasia: prenatal three-dimensional ultrasound findings.

Abstract

Diastrophic dysplasia is a rare autosomal recessive inherited disorder characterized by micromelia, cleft palate, abnormal ears, xyphoscoliosis, limited joint mobility, talipes, varus deformity of the great toes and distinctive abduction of the first metacarpals (‘hitchhiker’ thumbs)1, 2. It is thought to arise from mutations in the diastrophic dysplasia sulfate transporter gene, located on chromosome 5q32-q33.1, resulting in insufficient sulfation of cartilage proteoglycans3. This condition is remarkably common in the Finnish population (carrier frequency of approximately 1 in 70), which has accounted for more than half of the cases reported to date4. Prenatal diagnosis of diastrophic dysplasia was first reported in the early 1980s in pregnancies at risk for the condition, using two-dimensional (2D) ultrasound with or without the adjunctive use of fetoscopy5-7. Subsequently, with improving image resolution, ultrasound alone has become the method of choice to establish a confident prenatal diagnosis in both the high- and low-risk populations8-14. In this report we describe a case of diastrophic dysplasia diagnosed in a low-risk pregnancy, which was evaluated prenatally with three-dimensional (3D) ultrasound. A 37-year-old woman, gravida 2 para 1, was referred at 22 weeks' gestation following the detection of several fetal anomalies at the detailed second-trimester scan. Her medical history was unremarkable and there was no history of consanguinity or previous genetic disorders in the family. Ultrasound examination at referral revealed a singleton male fetus in breech presentation, a high posterior placenta and normal amniotic fluid volume. Measurements of the fetal head and abdomen were consistent with gestational age, but all long bones were markedly short, below the third centile for gestational age. In addition, several other anomalies were detected, including a lemon-shaped skull, xyphoscoliosis, bilateral talipes, ‘Buddha’ position of the lower limbs and fixed abduction of both thumbs. The mineralization of the bones was normal, there was no evidence of fractures or bowing of long bones and the size of the thorax was within normal limits. After counseling the parents opted for prenatal chromosomal analysis, which revealed a normal 46,XY karyotype. Subsequent 3D ultrasound evaluation (Voluson 730 real-time 4D ultrasound system, GE Medical Systems, Milwaukee, WI, USA) the following week confirmed severe micrognathia, small nose, thoracolumbar xyphoscoliosis, talipes and severe shortening of long bones with hitchhiker thumbs (Figure 1). At 26 weeks, the woman complained of absent fetal movements and ultrasound confirmed intrauterine demise. Labor was induced and a male stillborn infant weighing 620 g was delivered spontaneously. Postmortem examination was declined but clinical and X-ray examination confirmed the prenatal findings (Figure 2). Three-dimensional sonographic features of diastrophic dysplasia at 23 weeks' gestation. (a) Facial dysmorphism with severe micrognathia and small nose. (b) Shortening of upper limb with hitchhiker thumb. (c) Short, deformed lower limbs in ‘Buddha’ position and severe talipes. (d) Thoracolumbar xyphoscoliosis. Photograph of the stillborn infant showing severe micrognathia, small nose, micromelia, talipes and abducted (hitchhiker) thumbs and great toes. This report describes the prenatal 3D ultrasound findings in a case of diastrophic dysplasia. According to a Medline search using the terms ‘diastrophic dysplasia’, ‘diastrophic dwarfism’ and ‘prenatal diagnosis’, 10 prenatally diagnosed cases have been published in the English-language literature5-14. Our case seems to be the first to be evaluated in utero with 3D ultrasound. Diastrophic dysplasia is considered a severe although not lethal malformation1, 2. However, affected patients are at risk for upper airway obstruction due to laryngotracheal stenosis, with a mortality rate as high as 25% in early infancy1. In addition, the severity and multiplicity of the skeletal malformations are associated with significant physical handicap requiring extensive and continuous physiotherapy and orthopedic surgery1, 2. Prenatally, the most striking findings are marked shortening of the long bones and scoliosis. More detailed examination of the distal limbs will invariably reveal clubbed feet and fixed, bilateral abduction of the thumbs and toes, which are considered pathognomonic features of this disorder. The list of differential diagnoses is extensive and includes camptomelic dysplasia, thanatophoric dysplasia, osteogenesis imperfecta, distal arthrogryposis, Larsen syndrome, multiple pterygium syndrome, Roberts syndrome, Kniest dysplasia, mesomelic dysplasia, chondrodysplasia punctata and achondrogenesis11, 12, 14. Although the characteristic features of diastrophic dysplasia have been recognized previously by 2D ultrasound, in our case 3D ultrasound provided clearer views of the limb anomalies, including the hitchhiker thumbs. In addition, prenatal 2D ultrasound evaluation of the fetal face was not informative whereas 3D ultrasound clearly depicted the facial dysmorphism associated with the condition. The advantages of 3D over 2D ultrasound could be clinically important, as demonstration of micrognathia and hitchhiker thumbs could easily be missed on 2D ultrasound11, 12 but are easily detected on 3D ultrasound, as shown in our case. This work was supported by Sociedad Profesional de Medicina Fetal ‘Fetalmed’ Limitada, Chile.