Potential Impact of Parental Origin of Inheritance on the Clinical Presentation of Familial Partial Lipodystrophy Type 2 Syndrome

• Published in: Clinical endocrinology (Oxford) Vol. 103; no. 4; pp. 504 - 512
• Main Authors: Gilio, Donatella, Besci, Ozge, Guidorizzi, Natália Rossin, Guler, Merve Celik, Simsir, Ilgin Yildirim, Pelosini, Caterina, Ceccarini, Giovanni, Demir, Korcan, Akinci, Baris, Santini, Ferruccio, Foss‐Freitas, Maria Cristina, Oral, Elif A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 16.07.2025
• Subjects: Adipose tissue; Adult; Body composition; Body Composition - genetics; Body fat; Fatty liver; Female; Hereditary diseases; Humans; Lamin Type A - genetics; Lipodystrophy; Lipodystrophy, Familial Partial - genetics; Liver diseases; Male; Maternal inheritance; Maternal Inheritance - genetics; Metabolism; Middle Aged; Pancreatitis; Paternal Inheritance - genetics; Phenotype; Phenotypes; Retrospective Studies; Young Adult; body composition; lean mass; LMNA; fat mass; partial lipodystrophy; parent‐of‐origin effect; dual X‐ray absorptiometry
• ISSN: 0300-0664; 1365-2265; 1365-2265
• DOI: 10.1111/cen.15303

Familial partial lipodystrophy type 2 (FPLD2) is a rare autosomal dominant disorder caused by pathogenic variants in the LMNA gene. The influence of parental inheritance on clinical presentation has not been fully explored. To investigate the influence of maternal versus paternal inheritance of LMNA variants on the clinical and metabolic phenotype of patients with FPLD2. This retrospective cohort study included 83 patients with FPLD2 from four different centres. Clinical, biochemical, and body composition data were analysed. Patients were grouped based on maternal (maternal inheritance group; n = 49) or paternal (paternal inheritance group; n = 34) inheritance of LMNA variants. Statistical comparisons were made between the groups. Patients in the maternal inheritance group had a younger current age (35 (33) vs. 48 (22) years, p = 0.042) and earlier diagnosis of lipodystrophy (22 (30) vs. 36 (25) years, p = 0.044) compared to those in the paternal inheritance group. Body fat percentages in the arms (23.8 (6.5) % vs. 21.0 (6.2) %, p = 0.034) and trunk (32.1 (10.3) % vs. 28.5 (6.1) %, p = 0.024) were higher in maternal inheritance group. Fatty liver disease (79% vs. 57%, p = 0.029) and pancreatitis (26% vs. 8%, p = 0.033) were more prevalent in paternal inheritance group. Parental lineage may influence the phenotype of FPLD2: patients with a maternally inherited LMNA variant tend to preserve more adipose tissue in the upper body, while those with a paternally inherited variant experience greater adipose tissue loss in that region, often associated with more severe metabolic complications. These findings highlight the importance of contemplating parental lineage as a relevant factor when evaluating the clinical presentation and management of patients with FPLD2.