Overview
Mowat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder characterized by intellectual disability and multiple congenital anomalies, primarily due to mutations in the ZEB2 (ZFHX1B) gene located at 2q22 23.Diagnosis
Key Diagnostic Criteria: Characteristic facial features (microcephaly, hypertelorism, broad eyebrows, prominent columella, pointed chin, uplifted earlobes), intellectual disability, seizures, agenesis of the corpus callosum, congenital heart defects, hypospadias in males 4.
Recommended Tests: Genetic testing for ZEB2 mutations, including analysis for deletions, translocations, and atypical mutations 234.
Grading: Clinical diagnosis supported by genetic confirmation; variability in presentation may lead to underdiagnosis 2.Management
First-Line Treatments: Management of specific congenital anomalies (e.g., surgical intervention for congenital heart defects 1, supportive care for seizures).
Adjunctive Treatments: Speech therapy for severely impaired speech, physical therapy for motor impairments, and multidisciplinary care addressing intellectual disability and behavioral issues 4.
Specific Interventions: No specific drug doses mentioned; individualized care plans based on clinical manifestations 4.Special Populations
Pediatrics: Focus on early intervention programs, including speech and physical therapy, and surgical management of congenital anomalies 4.
Comorbidities: Consider hydrocephalus and genitourinary anomalies, particularly hypospadias, in male patients with developmental delays 5.Key Recommendations
Genetic testing for ZEB2 mutations is essential for accurate diagnosis of Mowat-Wilson syndrome (Evidence: Moderate 23).
Multidisciplinary care teams should be involved early to address the diverse clinical needs, including surgical interventions for congenital heart defects and supportive therapies for developmental delays (Evidence: Moderate 4).
Families should be actively involved in decision-making processes, especially regarding invasive procedures like cardiac surgery, considering the variable quality of life outcomes (Evidence: Weak 1).References
1 de Sá Bittencourt Câmara Bastos C, Vale da Cruz L, Hirano Arruda Moraes L, Jornada Krebs VL, de Carvalho WB. Outcomes of heart surgery in neonates with trisomy 13 and 18: a systematic review with metanalysis. European journal of pediatrics 2025. link
2 Engenheiro E, Møller RS, Pinto M, Soares G, Nikanorova M, Carreira IM et al.. Mowat-Wilson syndrome: an underdiagnosed syndrome?. Clinical genetics 2008. link
3 Zweier C, Horn D, Kraus C, Rauch A. Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype. American journal of medical genetics. Part A 2006. link
4 Adam MP, Schelley S, Gallagher R, Brady AN, Barr K, Blumberg B et al.. Clinical features and management issues in Mowat-Wilson syndrome. American journal of medical genetics. Part A 2006. link
5 Garavelli L, Cerruti-Mainardi P, Virdis R, Pedori S, Pastore G, Godi M et al.. Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B). Report of three Italian cases with hypospadias and review. Hormone research 2005. link
6 Fahmi F, Schmerler S, Hutcheon RG. Hydrocephalus in an infant with trisomy 22. Journal of medical genetics 1994. link