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

owat 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. 1The 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.Ka ¨a ¨ria ¨inen et al reported five patients with a similar phenotype. 5Mutations 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. 6Mutations in ZFHX1B (SIP1) were also identified by Cacheux et al 7 in two patients of Ka ¨a ¨ria ¨inen et al 5 : 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. 9Investigation of four patients by Zweier et al 10 and one patient by Garavelli et al 11 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 13Although 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 (SIP1). CLINICAL DESCRIPTION Patient 1This boy was the first child of unrelated parents.The sister was healthy.He was born at 41 weeks' gestation with a birth weight of 3200 g (10th-25th centile), a length of 48 cm (10th), and a head circumference of 33 cm (3rd-10th).Hirschsprung disease (HSCR) was diagnosed on day 2; a colostomy was carried out on day 3 and closed at 8 months.He had serious constipation from the first months of life and also a high degree of vescicoureteric reflux.At 14 months, hypotonia and psychomotor developmental delay was observed.Because of facial abnormalities a karyotype was performed, with normal results.He developed seizures at 16 months, when EEG showed epileptic anomalies prevailing on the right hemisphere, and sodium valproate therapy was started.On examination at 5 years of age, the boy showed several minor facial anomalies: fine hair, high forehead, frontal bossing, broad nasal bridge, medially flaring thick eyebrows, . . . . . . . . .