Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature

Abstract

Background: Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature ageing disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Classical and atypical forms of HGPS have been reported and there are clinical overlaps with mandibulo-acral dysplasia and restrictive dermopathy. To date, mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. Correlations between genotype and phenotype in children with progeroid syndromes are beginning to emerge.

Objectives: To establish whether the LMNA p.G608G mutation is associated with a particular phenotype of HGPS.

Methods: We reviewed the clinical features and skin histology of three children with HGPS associated with the p.G608G LMNA mutation, and compared our findings with those reported in the literature.

Results: Our patients shared a very similar presentation and clinical course. Skin changes were the earliest finding in all three. Skin histology showed nonspecific changes only.

Conclusions: The LMNA p.G608G mutation results in a uniform phenotype through early to mid-childhood, in keeping with that described in classical HGPS. Skin changes are the earliest distinctive clinical finding and should prompt careful physical and radiological examination for other features of HGPS. Skin biopsy for histology is not a useful investigation when a diagnosis of HGPS is suspected.