mowat - wilson syndrome ( mws ) ( mim#235730 ) is characterized by a typical facies , severe mental retardation , epilepsy , and variable congenital malformations , including hirschsprung 's disease ( hscr ) , genitourinary abnormalities , congenital heart disease , and agenesis of the corpus callosum . mws is caused by de novo heterozygous mutations or deletions in the zinc finger homeobox 1b gene ( zfhx1b ) located in the 2q22 region . zfhx1b encodes the smad - interacting protein-1 ( smadip1 or sip1 ) , a transcriptional corepressor involved in the transforming growth factor - beta signaling pathway . over 100 mutations have been described in patients with typical features of mws ; these have essentially been truncating mutations ( nonsense or frameshift ) or large deletions of the zfhx1b gene , suggesting a haploinsufficiency mechanism . we present the clinical data and the molecular analysis of a 2-year - old moroccan boy with mowat - wilson syndrome who was born to consanguineous parents . the patient was the first boy born to healthy consanguineous parents , both 29 years old , with no relevant familial history . the pregnancy and delivery were normal and the child was born at term , with normal weight , length , and head circumference . he had normal passing of meconium in the first 24 h of life , and no history of chronic constipation was reported . in the neonatal period , he developed seizures . he could hold his head up at 10 months , sit by himself at 24 months , and was not yet walking . at 2 years of age he presented with striking dysmorphic features : square - shaped face with a prominent but narrow triangular chin , plagiocephaly , thick eyebrows , sunken eyes , hypertelorism , broad nasal bridge , saddle nose , prominent columella , open mouth , and large uplifted ear lobes [ figure 1 ] . facial phenotype of the patient mri scan of the brain revealed agenesis of the corpus callosum and cerebral hypotrophy . electroencephalogram ( eeg ) , echocardiography , and genitourinary ultrasound examinations were normal . since the patient presented with typical dysmorphic features , severe developmental delay , epilepsy , and agenesis of the corpus callosum we suspected a mws , and molecular analysis of the zfhx1b gene this analysis led to the identification of a novel heterozygous nonsense mutation , c.1165a > t ( p.lys389x ) in exon 8 of the zfhx1b gene . at the time of diagnosis , the mother of the patient was 8 months pregnant . mowat - wilson syndrome , first clinically delineated by mowat et al . in 1998 , is a rare mental retardation - multiple congenital anomalies syndrome associated with typical facial dysmorphism , including hypertelorism , medially flared and broad eyebrows , enophthalmia , prominent columella , pointed chin , and uplifted earlobes , which typically prompts the clinician to consider the diagnosis . patients can present a variety of other anomalies , such as short stature ( 50% ) ; microcephaly ( 84% ) ; hscr ( 50% ) ; chronic constipation ( 25% ) ; malformations of the brain , particularly agenesis of the corpus callosum ( 60% ) ; seizures ( 75% ) , with no predilection for any particular seizure type ; congenital heart defects ( 75% ) ; and urogenital anomalies , particularly hypospadias ( 55% ) . in our patient , suspicion of mws was based essentially on the dysmorphic features associated with severe mental retardation and seizures . absence of microcephaly , hscr , congenital heart defect , and hypospadias did not preclude the diagnosis . several differential diagnoses of mws can be evoked . in patients with mental retardation ( mr ) , microcephaly , and hscr , born to consanguineous parents , the goldberg - shprintzen syndrome ( goshs ) , a rare autosomal recessive disorder , can be suspected if associated with specific dysmorphia . severe mr , seizures , ataxia , microcephaly , a prominent jaw , and a happy behaviour phenotype are also features of angelman syndrome . finally , pitt - hopkins syndrome can be considered in patients with mr , characteristic facial gestalt , and episodes of hyperventilation . in mws , the zfhx1b gene mutations are most often truncating ( nonsense , frameshift , or deletions ) and no obvious genotype - phenotype correlation has been identified so far . in a few cases , few recurrent mutations ( 6/100 ) have been identified . as this disorder is sporadic , with the mutations occurring de novo as the genetic counseling of mws is reassuring , it is important to evoke this diagnosis , particularly in consanguineous families . in our case ,
mowat - wilson syndrome is a mental retardation - multiple congenital anomaly syndrome characterized by a typical facies , developmental delay , epilepsy , and variable congenital malformations , including hirschsprung disease , urogenital anomalies , congenital heart disease , and agenesis of the corpus callosum . 
 this disorder is sporadic and is caused by heterozygous mutations or deletions of the zfhx1b gene located in the 2q22 region . 
 we report here the first moroccan patient , born to consanguineous parents , with mowat - wilson syndrome , due to a de novo , unreported mutation of the zfhx1b gene .