P18 ZMPSTE24 variant with the lethal phenotype of restrictive dermopathy.

Abstract

Restrictive dermopathy (RD) is a rare, lethal, congenital autosomal recessive laminopathy syndrome characterized by generalised tight translucent skin, dysmorphic facies, arthrogryposis multiplex congenita, and pulmonary hypoplasia. It is caused by mutations in either ZMPSTE24 or LMNA. Variants in these genes, which disrupt the production of lamin A, and hence the structural integrity of the nuclear envelope, can also cause survivable syndromes such as mandibuloacral dysplasia (MAD). We report the first son of non-related Caucasian parents delivered via emergency LSCS at 34 weeks following preeclampsia, gestational diabetes and polyhydramnios. Extraction was difficult due to arthrogryposis. At birth (weight 1.65 kg), he showed the typical features of RD. Genetic testing revealed a homozygous pathogenic ZMPSTE24 frameshift variant c.1085dup p. (Leu362PhefsTer19) previously reported in mandibuloacral dysplasia (Agarwal AK, Fryns JP, Auchus RJ, Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet 2003;12:1995-2001). Parents were heterozygous carriers. The baby received palliative care and died on day 2. The longest survival in RD is 120 days, in contrast to other laminopathies. Similar or identical mutation within the LMNA gene produces varied phenotypes which expands the spectrum. Currently, there is no curative therapy for RD. Our main aim to diagnose this condition is to offer counselling, genetic testing for future pregnancies, prevent unnecessary interventions and support the family through compassion and dignity.