Mowat-Wilson Syndrome As Seen through the Eyes of the Modern Mother
: A 14-month-old male patient who presented with multiple congenital anomalies was diagnosed with a novel mutation clinically compatible with a rare syndrome. Patient was born by C-section to a G3P2A1 mother at 38 weeks of gestation. Pregnancy was complicated by prenatal diagnosis of hydronephrosis and suspected ambiguous genitalia documented by ultrasound. Immediately after birth, he was admitted to the Neonatal Intensive Care Unit due to suspected Congenital Adrenal Hyperplasia. This diagnosis was ruled out and diagnosis of peno-scrotal hypospadia (Grade 4) was done. Karyotype revealed 46, XY complement. Failure to pass meconium after 24 hours, KUB with diffuse bowel dilation and marked abdominal distention suggested Hirschsprung disease. Aganglionosis was confirmed by biopsy and colostomy was performed at seven days old. Further evaluation included a head sonogram that revealed dysgenesis of corpus callosum, later confirmed by MRI. Patient was discharged in stable condition with appointments for evaluation by several specialists, including genetics follow-up.
In the meantime, patient's mother began to search on the internet and connecting all diagnoses provided, found he could have Mowat Wilson Syndrome (MWS). She got in touch with parental support groups and seeing pictures of other children supported her concerns. Formal evaluation by geneticist confirmed that all physical features were consistent with MWS: wide forehead with frontal bossing, laterally sparse eyebrows, hypertelorism and large eyes, prominent nasal tip, uplifted earlobes, open-mouthed expression, truncal hypotonia, equinovalgus deformity, and global developmental delay (Image 1, Image 2). Genetic testing was ordered and ZEB2 exon sequence analysis revealed a de novo heterozygous frameshift mutation (c.655_656dupGG, p.Tyr220Alafs*5) that had not been previously reported in patients with MWS and correlates clinically with this rare syndrome.
: MWS is a rare multiple congenital anomaly syndrome first described in 1998 caused by haploid insufficiency of the ZEB2 gene. Estimated prevalence is 1 in 70,000 births and only approximately 200 cases have been reported. Clinical features in this patient were consistent with those described for MWS: distinctive facial phenotype, hypospadia, Hirschsprung disease, and agenesis/dysgenesis of corpus callosum. This case highlights the importance of a multidisciplinary approach, including mom's intuition, in the evaluation of infants with multiple congenital anomalies. Parents using current technology have been instrumental in reaching a diagnosis of this rare condition that is often under-recognized by clinicians. Becoming familiar with the characteristic facial phenotype and clinical manifestations of MWS should help physicians recognize this syndrome. An early diagnosis is essential to improve health and developmental outcomes by prompt referral to early intervention services and appropriate clinical management.