Table 3.
Classification of FPLD based on genotype and/or phenotype
| FPLD type (#OMIM) | Genetic variant (*OMIM) and inherited pattern | Affected protein and main function | Phenotype | Time of onset and pattern of fat distribution |
|---|---|---|---|---|
| FPLD 1 (Köbberling syndrome) | Polygenic | Kob index > 3.47, truncal obesity, lipoatrophy of the limbs, “ledge” between normal and lipodystrophic areas [43, 27] | Adulthood | |
| FPLD 2 (Dunnigan syndrome) (#151660) |
LMNA (*150330) AD |
Lamin-A/C | Double chin with fat depots in the face, neck, supraclavicular regions, and genitalia; muscular appearance in the limbs; phlebomegaly [2, 18, 47] | Childhood in females, early adulthood in males |
| FPLD 3 (#604367) |
PPARG (*601487) AD |
PPARG (adipogenesis) | Distal lipoatrophy, insulin-resistant diabetes with severe hypertriglyceridemia [16, 49] | Childhood and early adulthood |
| FPLD 4 (#613877) |
PLIN1 (*170290) AD |
Perilipin-1 (lipid storage in droplets) | Lower limb lipoatrophy (anti-perilipin antibodies) [48] | Childhood or adulthood |
| FPLD 5 (#615238) |
CIDEC (*612120) AR |
CIDEC-3 (lipid droplet fusion) | Loss of subcutaneous fat from the limbs, diabetes mellitus with insulin resistance [39, 87] | Childhood |
| FPLD 6 (LIPE-associated lipomatosis) (#615980) |
LIPE (*151750) AR |
Hormone-sensitive lipase (HSL) | Distal lipoatrophy with multiple symmetric lipomatosis, insulin-resistant diabetes, and progressive myopathy [39, 87] | Adulthood |
| FPLD with MFN-associated lipomatosis (#151800) |
MFN2 (*608507) AR |
Mitofusin-2 (mitochondrial membrane fusion) | Lipoatrophy of the limbs with multiple symmetric lipomatosis, polyneuropathy, insulin resistance, and low levels of leptin and adiponectin [39, 87] | Early adulthood |
| FPLD 7 (#606721) |
CAV1 (*601047) AD |
Caveolin-1 (lipid droplet formation) | ||
| AKT2-related FPLD |
AKT2 (*164731) AD |
AKT2 (insulin receptor signalling) | Loss of subcutaneous fat from the limbs [39, 87] | Adulthood |
| ADRA2-related FPLD | ADRA2A | Adrenoreceptor α2A (Lipolysis) | Fat loss in trunk and extremities and increase of fat in face and neck [91] | Adulthood |
| FPLD type X | ND | ND | Kob index < 3.47, lipoatrophy of the limbs, insulin-resistant diabetes with severe hypertriglyceridemia | Early adulthood |
OMIM Online Mendelian Inheritance in Man (https://www.omim.org/), AR autosomal recessive, AD autosomal dominant, ND not determined