Progeroid features in a patient with Malouf syndrome due to a rare LMNA variant: a case report and review of the literature

TL;DR

A rare LMNA gene variant in a young woman caused a unique laminopathy with progeroid features and symptoms resembling Malouf syndrome.

Contribution

This case report identifies a novel laminopathy with progeroid features not typically associated with the LMNA genotype.

Findings

A de novo LMNA variant was found in a patient with progeroid features and Malouf syndrome-like symptoms.

The patient exhibited hypergonadotropic hypogonadism, prediabetes, and significant mitral annular calcification.

This case expands the clinical spectrum of LMNA-related disorders beyond typical progeroid syndromes.

Abstract

Laminopathiesrepresent a rare group of genetic disorders affecting various organs
and tissues, including the skin, muscles, adipose tissue, bone, and
cardiovascular system. The LMNA gene, the most common
pathogenic gene responsible for laminopathies, harbors variants that can lead to
diverse clinical phenotypes, such as progeroid syndromes, lipodystrophies,
muscular dystrophies, and cardiomyopathies. This report presents a case of a
young female patient who presented with prediabetes, secondary amenorrhea, and
secondary osteoporosis. A 28-year-old female presented to our clinic with
complaints of amenorrhea and decreased bone mineral density. She exhibited
pronounced facial abnormalities and underdeveloped secondary sexual
characteristics. Laboratory investigations revealed hypergonadotropic
hypogonadism, prediabetes and hyperlipidemia. Significant mitral annular
calcification was revealed via echocardiography. Genetic analysis revealed a
de novo variant in exon 1 of the LMNA
gene. This case reveals a novel laminopathy overlapping with the clinical
features of Malouf syndrome while also exhibiting additional progeroid features,
representing a distinct laminopathy. Furthermore, unlike previously reported
cases with this genotype, it does not correspond to a progeroid syndrome
typically associated with LMNA variants. Additionally, this case report is
accompanied by a review of the relevant literature.