• 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 …