Cornelia de Lange syndrome due to mosaic NIPBL mutation: antenatal presentation with sacrococcygeal teratoma

Abstract

A male infant at 36 weeks gestation was born by section. At 20 weeks of gestation, congenital diaphragmatic hernia and sacrococcygeal teratoma had been seen on ultrasound. At birth, the infant had features suggestive of Cornelia de Lange syndrome (CdLS). He remained hypoxic despite aggressive ventilatory manoeuvres and was palliated. At postmortem, the lungs were hypoplastic. In CdLS, mutations in NIPBL are found in around 50% of cases. Mutation analysis, including multiplex ligation dependent probe amplification of the NIPBL gene from the DNA extracted from peripheral blood lymphocytes was negative, but microarray comparative genomic hybridisation on DNA from skin fibroblast showed a 0.13Mb deletion on chromosome 5p13. The deleted region includes exons 42-47 of the NIPBL gene. It is important to perform NIBPL mutation analysis on DNA from more than one tissue when testing for CdLS.

A system‐based approach to the genetic etiologies of non‐immune hydrops fetalis

“…Sacrococcygeal teratomas are an especially common cause of NIHF, and reported genetic etiologies include MNX1 variants, partial monosomy 7q/trisomy 2p, and Cornelia de Lange syndrome . Other tumors occurring with NIHF include neuroblastomas, hemangiomas, fibrosarcomas, and rhabdomyosarcomas .…”

Differential Activation of Immune Effector Processes in Mature Compared to Immature Sacrococcygeal Teratomas

“…Little is known about the molecular features of SCT, and their pathogenesis remains unclear. Studies have predominantly shown normal karyotypes in pediatric SCTs [10,11], although a few cases have shown chromosomal abnormalities [12][13][14][15]. Expression of a subset of stem cells markers (NANOG, OCT4, SSEA-4 and nestin) has been found in SCT [9].…”