Cystic biliary atresia with paucity of bile ducts and gene mutation in KDM6A: a case report

Abstract

Background Biliary atresia (BA) cases are generally not associated with congenital abnormalities. However, accurate diagnosis of BA is often challenging because the histopathological features of BA overlap with those of other pediatric liver diseases and rarely overlap with those of other genetic disorders. We experienced a rare case of BA with the histopathological finding of bile duct paucity, a gene mutation in KDM6A , and KS-like phenotypes. Case presentation A male baby was diagnosed with biliary atresia by intraoperative cholangiography at 4 days of age, and histological examination following a liver biopsy revealed a paucity of bile ducts and several typical clinical findings of Alagille syndrome. However, Alagille syndrome was ruled out after neither JAG1 nor NOTCH2 gene mutations were identified. Whole-exome sequencing on DNA from his parents was additionally performed to examine other possible syndromic disorders, and a mutation was identified in KDM6A . However, Kabuki syndrome was not diagnosed as a result. The histological finding of interlobular bile duct paucity and the genetic mutation in KDM6A , as well as several clinical findings consistent with Alagille syndrome or Kabuki syndrome, made it difficult to confirm the diagnosis of BA. Conclusions Based on the interesting findings of the present case, we hypothesized that KDM6A is associated with hepatic malformations via a connection with the Notch signaling pathway.

Prenatal phenotype of Kabuki syndrome: A case series and literature review

“…Ultrasound scans showed a range of abnormalities including increased nuchal translucency, pleural effusion, cardiac anomaly, renal anomalies, intrauterine growth restriction, polyhydramnios, oligohydramnios and single umbilical artery. Similar antenatal presentations were also noted in the recent large case series and published case reports 8–40 . More than half of the cases were diagnosed after birth by clinical assessment and molecular testing.…”

Pathogenic Novel Heterozygous Variant c.1076c>T p. (Ser359Phe) chr1: 120512166 in NOTCH2 Gene, Type 2 Alagille Syndrome Causing Neonatal Cholestasis: A Case Report

“…Liver biopsy results can be confusing when diagnosing ALGS. Hence, a newborn with HNF1 deficit due to a mutation in the HNF1 gene [ 39 ] or a KDM6A gene mutation has been reported to have cholestasis because of a lack of interlobular bile ducts, which is a classic sign of ALGS [ 40 ]. JAG1 mutations account for the majority of reported mutations, with NOTCH2 accounting for approximately 1% to 3% [ 41 , 42 ].…”

Vitamin D3 deficiency in babies and children with cholestasis

“…Although jaundice in newborns is common and to be expected, persistent jaundice at 14 will usually die within twelve to eighteen months after birth (Song et al, 2012;Squires et al, 2020). Furthermore, biliary atresia can be a clinical characteristic of several hereditary disorders (Sanchez-Valle et al, 2017), including Mitchell Riley syndrome (Calcaterra et al, 2021), Fanconi anaemia complementation group Q (Bogliolo et al, 2013), Zimmermann Lab and syndrome 1, Alagille syndrome (Diaz-Frias & Kondamudi, 2022) and Kabuki syndrome 1 (Masui et al, 2019). Progressive familial intra-hepatic cholestasis and biliary hypoplasia are two other bile duct anomalies that mimic the medical signs of obstructive jaundice with biliary atresia (Gomez-Ospina et al, 2016; Sambrotta et al, 2014).…”