Mowat–Wilson syndrome and mutation in the zinc finger homeo box 1B gene: a well defined clinical entity

• Mowat–Wilson syndrome
• Hirschsprung disease
• ZXHX1B

• HSCR, Hirschsprung disease

Mowat et al in 1998 delineated a new syndrome characterised by a distinct facial phenotype, Hirschsprung disease (HSCR), microcephaly, and mental retardation; they also identified a locus at chromosome 2q21-q23.1 The six children described were sporadic cases, and the authors suggested a contiguous gene syndrome or a dominant single gene disorder. Three further sporadic cases published earlier as having unclassified syndromic HSCR, Goldberg–Shprintzen syndrome, or 2q22-23 deletion,2–4 were recognised by Mowat et al having the same distinctive facial appearance as their patients. Kääriäinen et al reported five patients with a similar phenotype.5 Mutations in ZFHX1B (SIP1) were identified by Wakamatsu et al in a patient with a translocation t(2;13)(q22;q22) and in another three patients, all with syndromic HSCR.6 Mutations in ZFHX1B (SIP1) were also identified by Cacheux et al7 in two patients of Kääriäinen et al5: patient 1 with a t(2;11)(q22.2;q21) and in patient 3; and in patients 1,2, and 3 of Mowat et al.1 Subsequently Yamada et al reported ZFHX1B mutations in other patients with complex developmental disorders,8 as did Amiel et al in patients with syndromic Hirschsprung disease.9 Investigation of four patients by Zweier et al10 and one patient by Garavelli et al11 showed the distinct phenotype and the mutation in ZFHX1B (SIP1) and confirmed the syndrome described by Mowat et al.1 Recently an article by Wilson et al reported 15 new patients with ZFHX1B mutations, and a review of Mowat–Wilson syndrome was published by Mowat et al.12,13

Although in total 45 cases with deletions or mutations in ZFHX1B (SIP1) have been recorded,4–14 detailed clinical descriptions are rare. We report two new patients from Northern Italy with all the typical signs of the syndrome and with mutations in ZFHX1B …