ESPE Abstracts

Background: Progeria syndromes caused by LMNA gene variants consist of Hutchinson-Gilford progeria syndrome (HGPS) and Atypical progeroid syndrome (APS). Various phenotypes of APS are previously reported, whereas HGPS shows relatively unique phenotype.

Objective: To investigate the spectrum of clinical manifestations in three cases of Progeria syndrome.

Methods: The history and clinical picture of three cases of Progeria syndrome experienced at our hospital were reviewed retrospectively.

Results: Case 1 was a 22-year-old woman. She was noted to have failure to thrive in infancy, and skin thinning at 1 year of age. Clinical diagnosis was made as Progeria syndrome at 7 years of age based on skin findings and facial appearance. She had decreased early insulin response at 8 years of age and high LDL cholesterol levels at 9 years of age. She had spontaneous menarche at 12 years old with scarce breast fat; the percent whole body fat was 23% at 16 years of age although the fat accumulation was low in the limbs. Case 2 is a 5-year-old girl. She showed poor weight gain in early infancy and decreased subcutaneous fat at around 2 years of age, suggesting progeria syndrome. Low subcutaneous fat was revealed on MRI before the age of two. Liver dysfunction, insulin resistance and body fat percentage of 15% was detected at 3 years of age. Progressing hair loss are being observed after 2 years old. Case 3 is a 2-year-old boy. He had poor weight gain from birth, scleroderma-like skin from 2 months, short stature below -2 SD at 5 months, alopecia, decreased early insulin response and body fat percentage of 20.5% at 1 year of age. All three cases had LMNA gene mutations; in case 1, p.C558R was identified at 18 years of age, in case 2, p.D136Y at 3 years of age and both were novel variants. Case 3 had a point mutation of p.G608G within the LMNA gene exon11, which was typical in HGPS.

Discussion: Case 3 had the typical presentation of HGPS. Of the two APS cases, case 2, in which insulin resistance and fatty liver was discovered earlier, had lower body fat percentage, which suggested that the amount of adipose tissue loss might have an influence on the phenotype. Two cases of APS had novel mutations in the LMNA gene respectively. Regarding genotype-phenotype association, future follow-up of the clinical picture and accumulation of cases are needed.