Focal Dermal Hypoplasia: Report of a Case with Myelomeningocele, Arnold–Chiari Malformation and Hydrocephalus with a Review of Neurologic Manifestations of Goltz Syndrome

Abstract

Focal dermal hypoplasia (Goltz syndrome, Online Mendelian Inheritance in Man [OMIM] 305600) is a rare X-linked dominant congenital disorder involving defects of mesodermal- and ectodermal-derived structures. It is associated with mutations in the PORCN gene, a regulator of Wnt signaling proteins. The phenotype is highly variable, although all describe characteristic skin findings as a primary diagnostic feature. To date there are few case reports of focal dermal hypoplasia associated with central nervous system abnormalities. We report the second case of focal dermal hypoplasia associated with myelomenigocele, Arnold-Chiari malformation and hydrocephalus and the first in a male. Genetic testing identified a novel mosaic three base pair deletion within the PORCN gene (c.853_855delACG). This case highlights the importance of neurological evaluation in focal dermal hypoplasia and consideration of other syndromes more commonly associated with central nervous system abnormalities. In this report we summarize the literature on neurological manifestations in Goltz syndrome.

Mosaicism due to postzygotic mutations in women with focal dermal hypoplasia

“…Mosaicism in surviving male patients is well described in X‐linked, male‐lethal disorders such as FDH . This study may give us a hint about the underestimated occurrence of this phenomenon in affected women, because some cases of mild involvement may previously have gone unnoticed.…”

“…Due to random X‐chromosome inactivation (lyonization) in female patients, the phenotype is expressed in a blaschkoid pattern . In male patients, either postzygotic mutations or a gonosome constitution of XXY (Klinefelter syndrome) can account for survival. In female patients, postzygotic mutations of PORCN have occasionally been reported .…”

Goltz syndrome in males: A clinical report of a male patient carrying a novel PORCN variant and a review of the literature

“…Goltz syndrome (GS), also known as Focal dermal hypoplasia (OMIM #305600), is a rare X‐linked dominant syndrome with variable meso‐ectodermal abnormalities 1. Common clinical findings concern the skin (patchy skin aplasia, subcutaneous fat herniation, papilloma, telangiectasia, sparse hair, syndactyly, dysplastic nails, linear hypo‐/hyperpigmentation often following the lines of Blaschko), skeleton (ectrodactyly, oligodactyly, transverse limb defects, long bone reduction defects), eyes (anophtalmos, microphthalmia, cataract, choroid or retinal coloboma), and face (facial asymmetry, hypoplastic alae nasi, abnormal ear morphology, and dental defects) 2…”

Focal dermal hypoplasia (Goltz Syndrome): A cross-sectionalstudy from Eastern India

“…Neurological manifestations in the form of myelomeningocele, Arnold–Chiari malformation, and hydrocephalus have been reported in association with FDH. [ 14 ] Approximately 40% of cases with Goltz syndrome may have ocular abnormalities in the form of coloboma, microphthalmia, and recurrent papillomas arising from the conjunctiva and lid margins. Aniridia, as seen in our patient, is an extremely rare ocular finding of Goltz syndrome.…”