Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 2, 42

Mowat-Wilson Syndrome

Affiliations
Review

Mowat-Wilson Syndrome

Livia Garavelli et al. Orphanet J Rare Dis.

Abstract

Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical investigation with intervention of several specialists (including neonatologists and pediatricians). Psychomotor development is delayed in all patients, therefore rehabilitation (physical therapy, psychomotor and speech therapy) should be started as soon as possible.

Figures

Figure 1
Figure 1
Mowat-Wilson Syndrome, clinical features of Patient 1 at age: (A) 1 year and 6 months; (B-C) 5 years; (D-E) 13 years and 8 months; (F-G) 18 years.
Figure 2
Figure 2
Mowat-Wilson Syndrome, clinical features of Patient 2 at age: (A) 1 year and 6 months; (B-C) 3 years and 5 months; (D-E) 8 years and 1 month.
Figure 3
Figure 3
Mowat-Wilson Syndrome, clinical features of Patients 3 and 4 at age: Patients 3: (A) 1 year and 2 months; (B) 3 years and 4 months; (C) 8 years and 1 month; Patients 4: (D) 3 years; (E) 3 years; (F) 3 years and 6 months.
Figure 4
Figure 4
Main common features of the patients with Mowat-Wilson Syndrome: uplifted ear lobes as "orecchiette pasta" or "red blood corpuscles".
Figure 5
Figure 5
Main common features of the patients with Mowat-Wilson Syndrome: large eyebrows, medially flaring and sparse in the middle part.
Figure 6
Figure 6
Scheme of ZEB2 exons and corresponding protein structure adapted from Zweier et al [4], showing the position of the presented mutations. NZF, N-terminal zinc finger cluster; CZF, C-terminal zinc finger cluster; SBD, Smad binding domain; HD, homeodomain like segment. [5, 11, 15, 17, 28].

Similar articles

See all similar articles

Cited by 31 PubMed Central articles

See all "Cited by" articles

References

    1. Mowat DR, Croaker GDH, Cass DT, Kerr BA, Chaitow J, Adès LC, Chia NL, Wilson MJ. Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23. J Med Genet. 1998;35:617–623. - PMC - PubMed
    1. Wakamatsu N, Yasukazu Y, Kenichiro Y, Takao O, Nomura N, Taniguchi H, Kitoh H, Mutoh N, Yamanaka T, Mushiake K, Kato K, Sonta S, Nagaya M. Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. Nat Genet. 2001;27:369–370. doi: 10.1038/86860. - DOI - PubMed
    1. Cacheux V, Dastot-Le Moal F, Kääriäinen H, Bondurand N, Rintala R, Boissier B, Wilson M, Mowat D, Goossens M. Loss-of-function mutations in SIP1 Smad interacting protein 1 results in a syndromic Hirschsprung disease. Hum Mol Gene. 2001;10:1503–1510. doi: 10.1093/hmg/10.14.1503. - DOI - PubMed
    1. Cerruti-Mainardi P, Garavelli L, Pastore G, Virdis R, Pedori S, Godi M, Provera S, Rauch A, Zweier C, Castronovo C, Zollino M, Banchini G, Bernasconi S, Neri G. Mowat-Wilson syndrome and mutation in the Zinc Finger Homeo Box 1B Gene: a new syndrome probably under-diagnosed. Italian J Pediatr. 2005;31:116–125.
    1. Zweier C, Albrecht B, Mitulla B, Behrens R, Beese M, Gillessen-Kaesbach G, Rott HD, Rauch A. "Mowat-Wilson" Syndrome with and without Hirschsprung Disease is a distinct, recognizable Multiple Congenital Anomalies-Mental Retardation Syndrome caused by Mutations in the Zinc finger homeobox 1 B gene (ZFHX1B) Am J Med Genet. 2002;108:177–181. doi: 10.1002/ajmg.10226. - DOI - PubMed

MeSH terms

Feedback