Restrictive Dermopathy in a Turkish Newborn

Abstract

A 4-day-old boy presented with tight, translucent skin, prominent vessels, skin erosions, and dysmorphic findings, including hypertelorism, antimongoloid axis, sparse eyelashes and eyebrows, pinched nose, natal teeth, microretrognathia, and an "o-shaped" mouth. Multiple joint contractures, dysplastic clavicles, and thin ribs were also observed. He died at 2 weeks of age of respiratory distress. The patient was diagnosed as being affected with restrictive dermopathy, which is a rare, lethal genodermatosis caused by recessive mutations of the zinc metalloproteinase ZMPSTE24 gene or less frequently, by dominant lamin A/C gene mutations. Direct sequencing of the ZMPSTE24 gene was performed, and the most common, homozygous, inactivating mutation in exon 9 was identified in the patient (c.1085_1086insT; p.Leu362PhefsX19). Autosomal recessive transmission was confirmed by parental DNA analysis. After genetic counseling, a prenatal diagnosis could be performed during the subsequent pregnancy. ZMPSTE24 screening was performed by direct sequencing and fluorescent fragment analysis on DNA derived from a chorionic villus sample after exclusion of maternal contamination. The fetus had inherited both normal parental alleles, avoiding the recurrence of the disease.

Frame shift mutations of the ZMPSTE24 gene in two siblings with restrictive dermopathy

“…This condition is fatal in the neonatal period, with most of the affected infants dying within 2 months of their lives (Yesil et al, 2011). However, a report on an atypically mild case of RD caused by a homozygous LMNA mutation describes an infant from full-term pregnancy who died of respiratory failure at the age of 7 months (Youn et al, 2010).…”

Prenatal Diagnosis for Restrictive Dermopathy Caused by Novel Mutations in ZMPSTE24 Gene and Review of Clinical Features and Pathogenic Mutations Described in Literatures

“…Fetal RD may result in stillbirth or early neonatal death. Pregnancies with fetal RD are likely to develop abnormal amniotic fluid volume, premature delivery, preterm premature rupture of membranes, fetal distress, and intrauterine growth restriction (IUGR) and are generally diagnosed postnatally [12][13][14][15][16][17][18][19][20][21]. The exact pathogenetic mechanism of the fetal RD remains unclear, but it appears to involve a primary defect of collagen metabolism [22,23].…”

Phenotypic heterogeneity of ZMPSTE24 deficiency

“…This disease spectrum results from phenotypic heterogeneity of ZMPSTE24 mutations which result in varying degrees of enzyme activity (Barrowman, Wiley, Hudon‐miller, Hrycyna, & Michaelis, ). Those with little to no enzyme activity have the most severe of these disorders which is Restrictive Dermopathy (RD, OMIM #275210) (Ahmad et al, ; Happle et al, ; Kariminejad, Goodarzi, Thanh, & Wehnert, ; Li, ; Morais et al, ; Moulson et al ; Navarro et al, ; Navarro et al, ; Navarro et al, ; Yesil et al, ). Those with milder deficiency have the less severe disorder of Mandibuloacral Dysplasia with Type B Lipodystrophy (MADB, OMIM #608612) (Agarwal et al, ; Ahmad, Zackai, Medne, & Garg, ; Ben Yaou et al, ; Kwan, ; Miyoshi et al, ).…”