Epiphyseal punctate calcifications (stippling) in complete trisomy 9

Abstract

Epiphyseal punctate calcifications (or epiphyseal stippling) are rare nonspecific prenatal features resulting from abnormal calcium deposition in enchondral bone formation sites. This abnormality belongs to a clinically and genetically heterogeneous group named chondrodysplasia punctata (CDP). The various etiologies observed in CDP include inherited errors of metabolism and skeletal dysplasias, anomalies of vitamin K metabolism, maternal autoimmune disorder, rare but well-recognized syndromes, and chromosomal abnormalities (Irving et al., 2008).We report on the prenatal diagnosis of complete trisomy 9 in amniotic fluid sampled following the discovery of epiphyseal punctuations and multiple congenital anomalies on second trimester fetal ultrasound. The diverse etiologies associated with epiphyseal stippling as well as suggestions for prenatal work-up are discussed.Fetal ultrasound at 22 weeks' gestation in a 26year-old G1P0 woman revealed multiple anomalies including brachycephaly, cerebellar vermis agenesis, corpus callosum agenesis, cleft lip and palate, ear anomalies, clenched hands, right renal agenesis, sacral vertebral anomalies and epiphyseal stippling in the hips and knees (Figure 1a).The woman and her husband were unrelated. During the first trimester, nuchal translucency thickness was 1.3 mm for a crown-rump length of 51 mm. Maternal serum screening estimated the Down syndrome risk at 1 : 400. The prospective parents were counseled and adviced that prognosis was poor because of the combination of severe malformations discovered on fetal ultrasound. They requested termination of pregnancy, and labor was induced at 24 weeks' gestation.The parents gave their consent for postmortem examination. The male fetus presented with intrauterine growth retardation (biometric measurements were compatible with 20 weeks' gestation-weight: 572.9 g, length: 32 cm, and OFC: 21.5 cm). He had multiple anomalies including brachycephaly, blepharophimosis, medial cleft lip and palate, micrognathia, hypoglossia, low-set malformed ears, prominent nose, short neck, clenched hands and feet, hypoplastic nails, elbow dislocation and fixed flexion of the hips, imperforate anus, penoscrotal hypoplasia, right renal agenesis and ureteral duplication of the left kidney, linear insertion of the atrioventricular valves without defect, thymic hypoplasia, and adrenal hypoplasia.Skeletal radiographs revealed epiphyseal stippling of the superior and inferior epiphyses of the femora (Figure 1b) and a calcification in the right hypochondria suggestive of a liver calcification. In addition, dislocations of shoulder, ankle, and hip articulations as well as flexion deformities of the joints of the hands were observed. Thirteen rib pairs were also noted. Neuropathologic findings revealed agenesis of the corpus callosum and postero-inferior hypoplasia of the vermis. Sterol quantifications on amniotic fluid obtained during termination of pregnancy were normal. Amniotic fluid culture karyotype revealed trisomy 9 in all 34 metaphases examined. Interphase...

Fetal chondrodysplasia punctata associated with maternal autoimmune diseases: a review

“…CDP is also seen in association with chromosomal abnormalities such as Turner syndrome, Down syndrome, trisomy 18 (Edwards’s syndrome) and trisomy 9 6 , 7 and with maternal exposure to cytomegalovirus or rubella viruses.…”

Prenatal Diagnosis of Complete Trisomy 9 With a Novel Sonographic Finding of Heart Calcification

“…There are also some reports showing rare features such as abnormal calcification in the liver and hypochondral region. [1][2][3][4] Complete trisomy 9 was first described in 1973 from cultured lymphocytes in an infant with congenital heart defects, skeletal abnormalities, and severe dysmorphism. 5 Most cases of complete trisomy 9 result in spontaneous first-trimester abortion.…”