Mowat-Wilson syndrome with Hirschsprung′s disease and vaginal atresia: case report and literature review / 中华实用儿科临床杂志

Clinical phenotypes and gene characteristics of a patient diagnosed with Mowat-Wilson syndrome (MWS) with Hirschsprung′s disease (HSCR) and vaginal atresia in the Department of Neonatal Surgery, Beijing Children′s Hospital, Capital Medical University in March 2021 were analyzed retrospectively.The eight-month-old girl was admitted to the hospital with symptoms of constipation for nine days and abdominal distension for two days.Lower digestive tract radiography and rectal mucosa biopsy results suggested HSCR.The child also had specific facial features and motor development delay.Whole exome test showed a de novo heterozygous mutation, ZEB2 gene c. 2761C>T (p.R921*). After laparoscopic-assisted Soave procedure, the child had normal bowel movements, and no surgery-related compli-cations occurred during the follow-up period.The child′s motor development improved after rehabilitation treatment.According to literature review, 2 female cases show similar clinical manifestations to this girl, but the genotypes were different.This patient expands the clinical phenotype of ZEB2 gene pathogenicity.

Prenatal diagnosis of a fetus with Mowat-Wilson syndrome / 中华医学遗传学杂志

Objective@#To explore the genetic basis for a fetus featuring increased nuchal thickness.@*Methods@#Routine G-banding karyotyping and single nucleotide polymrophism array were carried out to detect genomic copy number variations (CNVs) in the fetus.@*Results@#The fetus was found to harbor a heterozygous 3.8 Mb deletion in the 2q22.2-q22.3 region encompassing the ZEB2 gene, which is closely associated with Mowat-Wilson syndrome (MWS).@*Conclusion@#Haploinsufficiency of the ZEB2 gene may predispose to MWS. Lack of knowledge regarding to the ultrasonographic features of MWS may lead to misdiagnosis of the syndrome.

Mowat-Wilson syndrome: neurological and molecular study in seven patients / Síndrome de Mowat-Wilson: estudo neurológico e molecular em sete pacientes

Objective To present a seven-cases serie of Mowat-Wilson syndrome (MWS). Method All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization. Results A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum (1/7). Conclusion Physicians who care for patients with mental retardation and epilepsy should be aware of SMW. .

Objetivo Apresentar uma série de sete casos da síndrome de Mowat-Wilson (SMW). Método Todos os pacientes com estudo positivo para a mutação ZEB2 foram avaliados por um geneticista e um neurologista, com a caracterização clínica e laboratorial. Resultados Todos apresentavam fácies peculiar e retardo mental. A escala de Denver II evidenciou intenso atraso em todos os aspectos, sobretudo motor fino e adaptativo. Microcefalia adquirida foi observada em cinco pacientes. Apenas um paciente não apresentava epilepsia, sendo esta focal e predominando no sono, sendo relatado estado de mal em três pacientes. A crise inicial estava associada à febre na maioria dos pacientes (4/6). O EEG evidenciou atividade epiléptica focal na maioria (5/7). Ao estudo de imagem foi observada agenesia total (4/7) e parcial do corpo caloso (1/7). Conclusão Médicos que lidam com pacientes com retardo mental e epilepsia devem saber distinguir as características peculiares da SMW. .

A case of Mowat-Wilson syndrome with developmental delays and Hirschsprung's disease

Mowat-Wilson syndrome is an extremely rare genetic disease that is characterized by intellectual disability, facial dysmorphism, Hirschsprung's disease, and other congenital anomalies. This disorder is caused by heterozygous mutations or deletions in the zinc finger E-box-binding homeobox-2 gene (ZEB2). Thus far, approximately 200 cases of Mowat-Wilson syndrome have been reported worldwide. In Korea, only one case with a 2q22 deletion, which also affects ZEB2, has been previously reported. Here, we describe a patient with Mowat-Wilson syndrome who presented with developmental delays, typical facial dysmorphism, and Hirschsprung's disease. Molecular analysis of ZEB2 identified a novel heterozygous mutation at c.190dup (p.S64Kfs*6). To our knowledge, this is the second report of a Korean patient with Mowat-Wilson syndrome that has been confirmed genetically.

Síndrome de Mowat-Wilson: caso clínico / Mowat-Wilson's syndrome: a case report

Introduction: Mowat-Wilson syndrome (MWS) is a very infrequent congenital polimalformative disorder, caused by mutations, deletions or insertions of the ZEB2 gene, which codify for a protein that is involved in the migration of the neural crest cells and the development of middle line structures. The inheritance pattern is autosomal dominant, haplo-insufficient. Objectives: To describe a case of Mowat-Wilson syndrome with typical phenotype. Clinical case: 8 year-old female, with special facie, hard to control seizures, ductus arteriosus, left pulmonary artery stenosis, constipation, severe retardation of psychomotor development and speech retardation. Differential diagnosis of Mowat Wilson syndrome is proposed. Conclusion: Mowat and Wilson syndrome is very rare not well-known; therefore it is important to communicate its features within the pediatric community. In this syndrome multiple organs and systems are involved, so a multidisciplinary approach is mandatory; in order to the objective of adequately intervening in the pathology of each patient, provide adequate information regarding the developmental expectations for the child and genetic and reproductive counseling to the parents.

Introducción: El síndrome de Mowat-Wilson (MWS) es un síndrome polimalformativo congénito de muy baja frecuencia causado por mutaciones, inserciones o deleciones del gen ZEB2, que codifica para una proteína que está involucrada en la migración de las células de la cresta neural y en el desarrollo de las estructuras de la línea media. El patrón de herencia es autosómico dominante, haploinsuficiente. Objetivo: Describir un caso con fenotipo característico de Síndrome de Mowat-Wilson. Caso clínico: Paciente femenino de 8 años, con facies especiales, síndrome convulsivo de difícil control, ductus arterioso, estenosis de la rama izquierda de la arteria pulmonar, estreñimiento, retraso severo del desarrollo psicomotor y del lenguaje en el cual se plantea el diagnóstico clínico de síndrome de Mowat-Wilson. Conclusión: El Síndrome de Mowat Wilson es un síndrome de baja frecuencia, poco conocido, por lo que es importante difundir sus características en la comunidad pediátrica. En este síndrome se afectan múltiples sistemas y órganos, lo cual requiere un manejo multidisciplinario con el objetivo de intervenir adecuadamente en la patología de cada paciente, dar adecuada información de las expectativas del desarrollo del niño y consejería genética y reproductiva la familia.

Mowat-Wilson syndrome in a Moroccan consanguineous family.

Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. This disorder is sporadic and is caused by heterozygous mutations or deletions of the ZFHX1B gene located in the 2q22 region. We report here the first Moroccan patient, born to consanguineous parents, with Mowat-Wilson syndrome, due to a de novo, unreported mutation of the ZFHX1B gene.