Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome

Abstract

Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH.

Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases with prenatally diagnosed echogenic kidneys? Prenatal findings in two families with 17q12 microdeletion syndrome and review of the literature

“…Interestingly, Goumy et al . had arranged whole gene testing of HNF1β prenatally, which identified a whole gene deletion; however, the confirmation of 17q12 microdeletion syndrome was made postnatally . Whole gene sequencing can be costly and time consuming and therefore may not be ideal for prenatal testing.…”

“…7 Recurrent microdeletion of 17q12 may also be associated with autism, 8 Mayer-Rokitansky-Kuster-Hauser syndrome (congenital absence of the uterus and upper part of the vagina), 9 and congenital diaphragmatic hernia. 10,11 Recently, there have been case reports of 17q12 microdeletion detected on prenatal array CGH testing in fetuses with hyperechogenic and enlarged kidneys with multicystic renal dysplasia and hydronephrosis. [11][12][13] We report four further pregnancies from two families postnatally diagnosed with 17q12 microdeletion syndrome who in retrospect had prenatal ultrasound findings consistent with the diagnosis.…”

Prenatal diagnosis of HNF1B‐associated renal cysts: Is there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?

“…Apart from diabetes mellitus and the highly heterogeneous renal phenotype, with the most common manifestations being hyperechogenic kidneys prenatally and renal cysts postnatally, HNF1B aberrations have been associated with several other clinical anomalies. These include agenesis or hypoplasia of the pancreas, impaired liver function, urogenital anomalies, electrolyte abnormalities, and diaphragmatic hernia …”

A Familial 14q32.32q32.33 Duplication/17p13.3 Deletion Syndrome with Facial Anomalies and Moderate Intellectual Disability

“…Imbalances of subtelomeric regions, including duplication, deletion, and combined duplication and deletion, have been related to DD/ID or multiple congenital anomalies [Darcy et al, 2011;Pallister et al, 2011;Zrnová et al, 2012;Carvalho et al, 2014;Goumy et al, 2015]. In this study, we describe a subtelomeric rearrangement resulting in a 14q32.32q32.33 duplication and 17p13.3 deletion syndrome.…”