Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B

Abstract

Mutations or deletions involving ZFHX1B (previously SIP1) have recently been found to cause one form of syndromic Hirschsprung disease (HSCR), associated with microcephaly, mental retardation, and distinctive facial features. Patients with the characteristic facial phenotype and severe mental retardation, but without HSCR, have now also been shown to have mutations in this gene. Mutations of ZFHX1B are frequently associated with other congenital anomalies, including congenital heart disease, hypospadias, renal tract anomalies, and agenesis of the corpus callosum (ACC). We present the clinical data and mutation analysis results from a series of 23 patients with this clinical syndrome, of whom 21 have proven ZFHX1B mutations or deletions (15 previously unpublished). Two patients with the typical features (one with and one without HSCR) did not have detectable abnormalities of ZFHX1B. We emphasize that this syndrome can be recognized by the facial phenotype in the absence of either HSCR or other congenital anomalies, and needs to be considered in the differential diagnosis of dysmorphism with severe mental retardation +/- epilepsy.

Mowat-Wilson syndrome: neurological and molecular study in seven patients

“…Seizure disorder is a very common manifestation found in approximately 70%-75% 9,16,17,18 of patients; in the present study, epilepsy was present in all but one patient. The patient who did not develop seizures was the youngest of the group, and we need to maintain follow up in order to watch for the potential future development of seizures.…”

“…No specific EEG pattern or cortical area was observed in our patients, but in one patient in this series, activation of EEG abnormalities during sleep was observed, as described previously 19 . Seizures tend to become easier to manage with age 17 . Severe seizures, however, were observed in three patients, with presence of status epilepticus, and all of our patients required follow up with the use of antiepileptic medications.…”

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

“…3,4 In 2002 Zweier et al 5 further delineated the phenotype of MWS with or without HSCR, invariably characterized by ZEB2 gene defects, and proposed that the condition be named Mowat-Wilson syndrome. More than 300 patients have been reported so far [6][7][8][9][10][11][12][13][14][15][16][17] (additional reviewed articles are listed in Supplementary File S1 online).…”

Recurrence of Mowat–Wilson syndrome in siblings with the same proven mutation

“…This condition, now designated Mowat-Wilson (MWS) syndrome, was subsequently shown to be caused by heterozygous mutations in the ZFHX1B gene [Cacheux et al, 2001;Wakamatsu et al, 2001]. A series of subsequent publications have further delineated the phenotype [Zweier et al, 2002;Mowat et al, 2003;Wilson et al, 2003;Ishihara et al, 2004]. Other common features described in these patients include agenesis of the corpus callosum, congenital heart malformations, and genital and urinary tract anomalies.…”