Introduction
Mowat-Wilson syndrome (MWS), also known as Hirschsprung disease-intellectual disability syndrome, is a rare genetic disorder caused by heterozygous pathogenic variants or deletions in ZEB2. There is yet no specific treatment, for ZEB2 gene mutation affects the early stages of embryonic neural crest formation in MWS. In this report, we present a case of MWS with improved functional outcome after umbilical cord blood (UCB) stem cell therapy.
Case report
A 10-month-old female infant was referred to our department. She was born with a full-term pregnancy, however could not creep or crawl until 10 months. She also had calyceal diverticulum, small ventricular septal defect and chronic constipation. Physical exam showed thumb-in-palm posture and spasticity of bilateral ankles. A brain MRI shows dilated ventricles with decreased white matter volume and thin corpus callosum. Under the interim diagnosis of cerebral palsy, she was enrolled in an allogeneic UCB transplantation trial.
Unrelated allogeneic UCB units were selected from UCB bank of our organization. The conditions for UCB selection were at least 4 out of 6 matching HLA typing for A, B, and DRB1 antigens. For allogeneic UCB injection, cyclosporine was administered intravenously for 1 week and orally for 3 weeks. After thawing and washing according to our protocol, UCB was infused intravenously at age of 13 months. Side effects associated with immune rejection were not observed during the hospital stay and no adverse effect related to neoplasm was reported. ZEB2 gene mutation in exon 5, c.502C>T was found by exon sequencing and confirmed the diagnosis of MWS five years after the UCB injection.
Figure 1 shows the results of the functional assessment. She was in GMFCS IV at the initiation of PT. The GMFM score increased gradually until the 26th month of age, which was 1 year after cord blood transplantation. During that period, GMFCS remained improved to III for approximately 1.5 years. Improvement was also observed in the BSID-II both in mental and motor scores. Epilepsy is known as a major manifestation of MWS, and the prevalence of epilepsy in MWS is about 70-75%. In one study, and the median age at seizure onset was 14.5 months. In this case, the first seizure episode occurred at the age of 3 years and there was no seizure event for 2 years after the injection. Diffuse tensor images in magnetic resonance imaging were taken 3 months before and 6 months after the procedure (Figure 2). The hypogenesis of corpus callosum was continuously observed, but the fiber density of both hemispheres including the corpus callosum increased at 6 months after injection.
Conclusion
In this MWS case, UCB stem cell injection was performed without significant side effects, and seemed to be effective. This suggests that the stem cell therapy may be considered as a therapeutic option in inherited neural developmental disorders. |
