Fetal hydrops, hyperechogenic arteries and pathological doppler findings at 29 weeks: prenatal presentation of generalized arterial calcification of infancy - a novel mutation in ENPP1.

Prenatal diagnosis of generalized arterial calcification of infancy (GACI) (OMIM #208000) is difficult and rare. There are various known gene mutations in ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) locus 6q22-q23. We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauterine therapy with bisphosphonates was considered, but delayed due to rapid deterioration in fetal Doppler flows with suspected fetal asphyxia. The couple was informed about the most unfavorable prognosis in fetal hydrops, however, they opted for elective delivery. A cesarean section was performed. Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.

Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect.

The Wilms tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and the gonads, and clinical syndromes associated with WT1 mutations, such as WAGR syndrome, Denys-Drash syndrome and Frasier syndrome, typically manifest as renal and genitourinary abnormalities. WT1 may also play an important role in the development of the diaphragm, and recently several papers have reported an association between WT1 mutations and diaphragmatic hernias. In addition, WT1 mutations were also detected in some patients with Meacham syndrome, a rare malformation syndrome comprising congenital diaphragmatic hernia, double vagina, sex reversal, and cardiac malformations. Here, we report a case of an infant with typical clinical features of Deny-Drash syndrome and a heterozygous missense mutation, Arg366His, in the WT1 gene, in whom a diaphragm defect was detected after starting peritoneal dialysis. Diaphragmatic defects are rare but may be considered as clinical manifestations of WT1 mutation syndromes. In addition, we suggest that WT1 abnormalities should be suspected in patients with chronic renal failure who develop hydrothorax after peritoneal dialysis, especially in those with genitourinary abnormalities.

Fetal therapy and cytogenetic testing: prenatal detection of chromosome aberration during thoracocentesis for congenital chylothorax by karyotyping from pleural effusion fluid and review of the literature.

This report serves to emphasize the necessity of rapid cytogenetic testing during fetal therapy for congenital hydrothorax and to review the literature. A 31-year-old primigravid woman was noted to have bilateral fetal hydrothorax, polyhydramnios, and preterm labor at 32 weeks' gestation. Echo-guided thoracocentesis was performed to draw 50 ml of golden/yellow pleural effusion fluid and 500 ml of amniotic fluid. Cytogenetic analysis of the lymphocytes obtained from the pleural effusion fluid revealed a karyotype of 47, XY, + 21. The pleural effusion fluid was predominantly lymphocytic and positive for the Rivalta test. A sonographic examination at 33 weeks' gestation revealed recurrent pleural effusion, but the woman refused repeat thoracocentesis and tocolytic management. A 2,568-g male baby with characteristic phenotypic findings of Down syndrome was delivered vaginally and expired after birth. The present case reinforces the notions that fetuses with congenital chylothorax are at risk for chromosomal abnormalities, and drainage of pleural effusion must include a rapid diagnosis of fetal karyotype. The cytogenetic information acquired is useful for genetic counseling and perinatal obstetric management.