Mowat-Wilson syndrome chromosome 2 deletions

Mowat-Wilson syndrome and chromosome 2 deletions

Mowat-Wilson syndrome (MWS) caused by mutations of the ZEB2 gene (or deletions of 2q22 chromosomal segment where this gene is located) is characterized by microcephaly, distinctive facial features, Hirschsprung disease, developmental delay, some other congenital anomalies, epilepsy, and behavioral problems. Recent publications by Liang et al. and Chung et al. have shown that individuals with interstitial duplications of 2q22.3 including the entire ZEB2 gene have distinctive craniofacial features in addition to having some of the features of MWS. The current paper by Liu et al. introduces a novel case with a de novo 22.16 Mb duplication at 2q21.2-q24.1 to further contribute to this syndrome differentiation between MWS and duplication syndrome including the entire ZEB2 gene. The patient is a 2.6-year-old Chinese girl noted for developmental and physical delay. She did not present with facial findings typical of MWS; instead she presented with distinctive craniofacial features including scaphocephaly, flat forehead and face, small eyes, slightly swollen upper eyelids, hypertelorism, sparseness of the whole eyebrows and hair, low nasal bridge, small nose, shallow philtrum, small and open mouth, thin upper lip, high arched palate, sparse teeth, micrognathia, low-set protruding ears, circular arc helix, dysplasia of auricle. She also had an atrial septal defect, dolichosigma, inguinal hernia, reduced volume of the frontal lobe, encephalomalacia, and delayed myelination.  Genetic workup yielded the de novo 22.16 Mb duplication at 2q21.2-2q24.1 including ZEB2 and 41 other OMIM listed genes. In a literature review with the two previous cases, it is noted that all three cases have similar craniofacial findings not typical for MWS. The authors further propose that patients with duplications 2q22 involving the ZEB2 have neurodevelopment delay (3/3), congenital heart diseases (3/3), behavioral problems (2/3), dental anomalies (2/3), behavioral problems (2/3), inguinal hernia (1/3), and urogenital anomalies (1/3). These presentations are common in MWS, but none of these individuals have the typical facial features of MWS. The authors suggest that whole ZEB2 dosage increase may cause multiple system abnormalities like MWS but through different mechanics. In summary, the authors further use this case to highlight a differentiation from MWS and recommend that this condition be refered to as Liu-Liang-Chung syndrome.

Liu et al. ““Liu-Liang-Chung” syndrome with multiple congenital anomalies and the distinctive craniofacial features caused by dominant ZEB2 gene gain mutation”.” BMC Pediatrics” 2023, v.23:480.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org