Restrictive dermopathy: two‐ and three‐dimensional sonographic features

Abstract

Restrictive dermopathy is a rare lethal genetic disorder characterized by tight and rigid skin, skin erosions and prominent superficial vasculature with epidermal hyperkeratosis. In addition, one may find microstomia, a small pinched nose, micrognathia and sparse/absent eyelashes and eyebrows, as well as mineralization defects of the skull, thin dysplastic clavicles and humeri, multiple joint contractures, intrauterine growth restriction and polyhydramnios. Associated anomalies of the viscera may include hepatosplenomegaly, ureteral duplication and pulmonary hypoplasia. Liveborn infants usually die within the first week of postnatal life1-6. It is caused by either autosomal dominant or autosomal recessive mutations of a gene that encodes a metalloprotease essential for the post-translational processing of prelamin A to mature lamin A, an important step in collagen synthesis6, 7. Approximately 47 cases of restrictive dermopathy have been reported worldwide8. Antenatal diagnosis has been reported in only three cases following a high index of suspicion based on family history2-4. We report a case in which typical features of restrictive dermopathy were seen antenatally in a pregnancy with no positive family history. A 35-year-old primigravid woman was seen at our center for maternal fetal medicine. She was a healthy Caucasian, and was not consanguineous with her husband. Her pregnancy course had been unremarkable; she had had a normal nuchal translucency scan. Karyotyping at 16 weeks' gestation showed a normal 46,XX. The anatomical survey at 20 weeks' gestation was normal. At 30 weeks' gestation a routine ultrasound examination revealed multiple fetal anomalies, including abnormal facial profile with a beak-like nose, micrognathia and microstomia, abnormal calvarium, hypertelorism and frontal bossing of the forehead (Figure 1a). In addition, the upper arms were permanently flexed and the hands remained open with the fingers spread out (Figure 2a). Sandal gap toes, ambiguous genitalia, moderate-to-severe fetal ascites and mild polyhydramnios were also documented. Even though a precise diagnosis was not provided antenatally, the patient was told that a severe and complex fetal malformation had been detected. After discussing the management options, the patient elected to terminate the pregnancy at 31 weeks. (a) Three-dimensional ultrasound image at 31 weeks' gestation showing a pinched nose, micrognathia and microstomia, abnormal calvarium, hypertelorism and frontal bossing of the forehead. (b) Profile of the fetus following termination at 31 weeks demonstrating the same features as those in (a). (a) Two-dimensional ultrasound image at 31 weeks' gestation showing a hand spread open. (b) Postmortem image showing hands open, with the fingers spread out. A female fetus weighing 1300 g was delivered. Autopsy revealed a thin, extremely taut and stretched-out skin, with total alopecia. Histological examination of the skin was consistent with restrictive dermopathy. All of the features identified on prenatal sonographic examination were confirmed on macroscopic examination (Figures 1b and 2b). No abnormalities of the internal organs were identified. Restrictive dermopathy was the final diagnosis. The differential diagnosis of restrictive dermopathy includes Rubinstein–Taybi syndrome and congenital skin disorders such as epidermolysis bullosa, aplasia cutis congenita, the lethal ichthyosis variant of arthrogryposis, and other severe congenital skin defects5, 9. It is known that the specific sonographic manifestations of restrictive dermopathy become evident only at the beginning of the third trimester2, 4. Hamel et al. performed skin biopsies at 20 weeks on several cases of restrictive dermopathy and could not demonstrate any skin abnormalities. They concluded that these abnormalities develop only later in fetal life10. The present case illustrates the prenatal appearance of restrictive dermopathy by providing two- and three-dimensional sonographic images of several malformations described in this syndrome. In our case the ability to produce a three-dimensional image of the face allowed us to demonstrate typical features including the small pointed nose, micrognathia, open fixed mouth and frontal bossing of the head. Once this syndrome is suspected, specific genetic testing and a definitive diagnosis are possible before delivery. N. Feldman-Leidner*, K. Delaney*, M. Malikina*, P. Segarra*, G. R. Tiller , T. Singer*, M. Y. Divon*, * Obstetrics and Gynecology, Lenox Hill Hospital, New York, NY, USA, Women's Health Care Services, Wichita, KS, USA