Clinical features and management issues in Mowat-Wilson syndrome.
Mowat-Wilson syndrome (MWS) is a relatively newly described multiple congenital anomaly/mental retardation syndrome. Haploinsufficiency of a gene termed ZFHX1B (also known as SIP1) on chromosome 2 is responsible for this condition, and clinical genetic testing for MWS recently became available. The majority of reports in the literature originate from Northern Europe and Australia. Here we report our clinical experience with 12 patients diagnosed with MWS within a 2-year period of time in the United States, with particular emphasis on clinical characteristics and management strategies. Individuals with this condition have characteristic facial features, including microcephaly, hypertelorism, medially flared and broad eyebrows, prominent columella, pointed chin, and uplifted earlobes, which typically prompt the clinician to consider the diagnosis. Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). The incidence of MWS is unknown, but based on the number of patients identified in a short period of time within the US, it is likely greatly under recognized. MWS should be considered in any individual with severely impaired or absent speech, especially in the presence of seizures and anomalies involving the pulmonary arteries (particularly pulmonary artery sling) or pulmonary valves.
Adam
Margaret P
MP
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA. madam@genetics.emory.edu
Schelley
Susan
S
Gallagher
Renata
R
Brady
April N
AN
Barr
Kimberly
K
Blumberg
Bruce
B
Shieh
Joseph T C
JT
Graham
John
J
Slavotinek
Anne
A
Martin
Madelena
M
Keppler-Noreuil
Kim
K
Storm
Andrea L
AL
Hudgins
Louanne
L
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000293:Adolescent; D000328:Adult; D061085:Agenesis of Corpus Callosum; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D007805:Language Development Disorders / Q000235:genetics; D008297:Male; D011651:Pulmonary Artery / Q000002:abnormalities; D012097:Repressor Proteins / Q000235:genetics; D012640:Seizures / Q000235:genetics; D013577:Syndrome; D000074165:Zinc Finger E-box Binding Homeobox 2
D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2