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. 2023 Feb 24;12(5):725.
doi: 10.3390/cells12050725.

Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review

Antia Fernandez-Pombo  1   2 , Everardo Josue Diaz-Lopez  1   2 , Ana I Castro  2   3 , Sofia Sanchez-Iglesias  1 , Silvia Cobelo-Gomez  1 , Teresa Prado-Moraña  1   2 , David Araujo-Vilar  1   2
Affiliations

Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review

Antia Fernandez-Pombo et al. Cells. .

Abstract

Type 2 familial partial lipodystrophy (FPLD2) is a laminopathic lipodystrophy due to pathogenic variants in the LMNA gene. Its rarity implies that it is not well-known. The aim of this review was to explore the published data regarding the clinical characterisation of this syndrome in order to better describe FPLD2. For this purpose, a systematic review through a search on PubMed until December 2022 was conducted and the references of the retrieved articles were also screened. A total of 113 articles were included. FPLD2 is characterised by the loss of fat starting around puberty in women, affecting limbs and trunk, and its accumulation in the face, neck and abdominal viscera. This adipose tissue dysfunction conditions the development of metabolic complications associated with insulin resistance, such as diabetes, dyslipidaemia, fatty liver disease, cardiovascular disease, and reproductive disorders. However, a great degree of phenotypical variability has been described. Therapeutic approaches are directed towards the associated comorbidities, and recent treatment modalities have been explored. A comprehensive comparison between FPLD2 and other FPLD subtypes can also be found in the present review. This review aimed to contribute towards augmenting knowledge of the natural history of FPLD2 by bringing together the main clinical research in this field.

Keywords: Dunnigan disease; FPLD2; LMNA; laminopathies; type 2 familial partial lipodystrophy.

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Conflict of interest statement

D.A.-V. has received honoraria as scientific advisor from Amryt Pharma. The rest of the authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lamin A processing pathway and laminopathies affecting mesenchymal tissues. Prelamin A is farnesylated, methylated and processed by ZMPSTE24, giving rise to the mature lamin A. Alterations in this lamin A processing pathway are responsible for several disorders known as laminopathies, which mainly affect mesenchymal tissues. In this figure, laminopathies are distributed according to the most characteristically affected mesenchymal tissue (adipose tissue in the case of type 2 familial partial lipodystrophy). MSC: mesenchymal stem cell.
Figure 2
Figure 2
Search strategy and flow diagram of articles.
Figure 3
Figure 3
Clinical features of Dunnigan disease. While there is a loss of adipose tissue from the trunk, buttocks and limbs, fat excess in the face and neck and muscle hypertrophy is evident in women with FPLD2; in men, this characteristic phenotype is not so apparent.
Figure 4
Figure 4
Comparative body composition determined by Dual-Energy X-ray Absorptiometry. Comparative, colour-mapped, total body composition scans via whole-body Dual-Energy X-ray Absorptiometry of patients with FPLD2, FPLD3 and non-lipodystrophic subjects. Green represents an area of low-level % fat (0–25%), yellow an area of medium-level % fat (25–60%), and red an area of high-level % fat (60–100%); (A) Less-pronounced fat loss can be observed in the woman with PPARG-associated FPLD in comparison with the women with FPLD2. Differences can be seen even when comparing different variants within exon 8 of the LMNA gene; (B) Differences in the distribution of adipose tissue are less evident in men with FPLD2 when compared with age and BMI-matched healthy or obese controls.
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