Abstract

The authors update on a previously reported patient with Mowat–Wilson syndrome (MWS) with unusual dermatological features including photosensitivity and skin dyspigmentation.1

An 18-month-old Afro-Caribbean boy with Hirschsprung's disease, hypospadias, delayed visual maturation, microcephaly, developmental delay, seizures and dysmorphic facial features was referred to the dermatology department. Since birth he displayed persistent skin dyspigmentation with patchy macular hypo- and hyperpigmentation involving the face and neck, upper limbs, trunk, perineum and right ankle. There was no history of preceding inflammation or eczema.

Following the original report, his parents have described photosensitivity since the age of 2 years, with sunburn-like erythema occurring within minutes of sun exposure despite application of high-factor sunblock. Investigations including lupus serology and porphyria screen were normal. The patient is currently awaiting formal phototesting. Genetic analysis previously identified a heterozygous truncating mutation in exon 8 of the ZEB2 (formerly ZFHXIB; Zinc finger homeobox 1B) gene, confirming MWS.

MWS was first described in 1998, comprising characteristic facial dysmorphism, profound learning difficulties, epilepsy, Hirschprung's disease and other congenital abnormalities, mapped to a locus at chromosome 2q21–q23.2 In 2001 the causative gene, ZEB2 was identified.3 Subsequently, over 100 pathogenetic heterozygous mutations or deletions are described.4 The distinctive evolving facial phenotype has been recently reviewed.5

ZEB2 encodes Smad interacting protein (SIP1), a ubiquitous transcription factor with an important role in embryological development including the neural crest. “Raindrop” pigmentation has been previously reported in a 9-year-old patient with MWS.6 This indicates that MWS should be added to the spectrum of neurocutaneous disorders comprising dyspigmentation and Hirschprung's. We can speculate that dyspigmentation results from ZEB2 haploinsufficiency disrupting neural crest melanocyte development or migration.

Our case is the first record of photosensitivity in MWS, raising the possibility of an additional role of ZEB2 in regulating the cutaneous response to ultraviolet radiation.