triglycerides and glycerophospholipids CGL2 : seipin, formation of lipid droplets AR () CGL3 CAV1:caveolin-1, formation of membrane caveolae, lipid traffic AR (single case) () CGL4 PTRF : cavin-1, formation of membrane caveolae, lipid traffic AR () associated PPARG: PPAR, transcription factor, adipocyte differentiation AR (single case) () AGL (Lawrence syndrome) Frequently associated with autoimmune diseases and/or complement abnormalities - () () Partial lipodystrophies FPLD1 genetic cause unknown Usually AD ()
LMNA : lamin A/C, structure and functions of nuclear lamina AD () () FPLD3 PPARG: PPAR, transcription factor, adipocyte differentiation AD () PLIN1: perilipin-1, structure and function of adipocyte lipid droplet AD () CIDEC : CIDEC, structure and function of adipocyte lipid droplet AR (single case) () FPLD6 LIPE : hormone sensitive lipase, regulation of lipolysis AR () () Akt2-linked lipodystrophy AKT2: Akt2, insulin signaling AD (single family) () APL Frequently associated with autoimmune - ()
syndrome) diseases, complement 3 nephritic factor and/or complement 3 abnormalities Progeroid and/or multisystem lipodystrophy syndromes progeria syndrome (HGPS) LMNA : A/C, structure and functions of nuclear lamina de novo () () Progeroid laminopathies LMNA : lamin A/C, structure and functions of nuclear lamina AD, de novo () dysplasia type A (with partial lipodystrophy) LMNA : lamin A/C, structure and functions of nuclear lamina AR () dysplasia type B (with generalized lipodystrophy) ZMPSTE24: Zinc metalloproteinase, prelamin A processing AR ()
MDP syndrome POLD1: subunit of DNA polymerase , DNA polymerization and repair de novo () Werner syndrome WRN: WRN DNA helicase, DNA repair AR () progeria Syndrome BANF1: Barrier to autointegration factor (BAF), required for the assembly of emerin and A-type lamins at the reforming nuclear envelope AR () Neonatal Marfan progeroid syndrome FBN1: fibrillin 1, connective tissue de novo () Syndrome KCNJ6 (GIRK2): inwardly rectifying potassium channel de novo () Ruijs-Aalfs syndrome SPRTN: SprT-like domain protein, DNA repair AR ()
Neonatal progeroid syndrome CAV1: Caveolin-1, formation of membrane caveolae, traffic de novo () Auto-inflammatory syndromes with lipodystrophy lipodystrophy (JMP, CANDLE) PSMB8: Proteasome (prosome, macropain) subunit, beta type, 8; (PSMB8); immunoproteasome subunit AR () Other syndromes with lipodystrophy SHORT PIK3R1: regulatory subunits of the phosphatidyl inositol-3 kinase of class IA insulin signaling AD, de novo () lipodystrophy PCYT1A: phosphate cytidylyltransferase 1 synthesis of phosphatidylcholine AR () linked
CGL 4 (PTRF) AR Almost all fat lost Normal mechanical Marrow fat unknown None Hypertrichosis Acromegaloid Percussion-induced muscle mounding Muscle weakness & hypertrophy Spinal rigidity ↑Lordosis Osteoporosis Atlanto-axial instability Arthritis Contractures Cardiac Risk of sudden cardiac IR Mild ↑glucose ↑TG ↓Leptin N N Hypertrophic pyloric stenosis Esophageal dysmotility ↑ALT/AST Not reported Failure to Umbilical prominence Transient Recurrent infections CGL AR Almost all fat lost None AN Phlebomegaly Eruptive xanthomata Muscle hypertrophy IR/DM ↑TG ↓Leptin N N Acute pancreatitis Irregular menses parathyroidism Acquired Generalized Lipodystrophy Onset ↓Fat ↑Fat Skin Muscle Bone Mineral Nervous GI Spleen GU Endocrine Other n/a n/a After birth, often before adolescence Almost all fat lost ↓Mechanical Normal marrow None AN Hirsutism Muscular appearance Ischemic ± HTN IR/ DM ↑ TG ↓ Leptin N N PCOS 3 variants: Panniculitis Autoimmune (complement abnormalities) Idiopathic
Familial Partial Lipodystrophy Subtype Onset ↓Fat ↑Fat Skin Appendages Muscle Bone Mineral Meta-bolic Kidney Nervous GI Liver Spleen GU Endocrine Other U Child- or Buttocks Face Neck Abd (sc + visc.) AN Phlebomegaly Eruptive xanthomata Hirsutism Calf hypertrophy Coronary artery disease HTN IR/DM ↑TG N N Hepatomegaly N Only ♀ reported (LMNA) AD Puberty Buttocks Limbs Face Neck Abd (visc.) AN Phlebomegaly Eruptive xanthomata Hirsutism Muscle hypertrophy Myalgia Coronary artery disease HTN IR/DM ↑TG Mild ↓Leptin Proteinuria in late stages Nerve entrapment syndromes Pancreatitis Hepatomegaly Hepatic steatosis PCOS Labial Breast hypoplasia Preeclampsia Miscarriages Lipomas FPLD3 (PPAR) AD Trunk Buttocks Limbs ±Abdomen AN Phlebomegaly Hirsutism Muscular appearance HTN IR/DM ↑TG Mild ↓Leptin N N Hepatomegaly Hepatic steatosis PCOS FPLD4 AD Child- or Buttocks Limbs ±Face AN Muscle hypertrophy HTN IR/DM ↑TG N N Hepatomegaly Hepatic steatosis PCOS Cushingoid appearance occasional FPLD5 AR Buttocks Lower limbs None AN Muscle hypertrophy HTN IR/DM ↑TG ↓Leptin Proteinuria N Pancreatitis Hepatomegaly Irregular menses Diabetic
Hepatic steatosis FPLD6 (LIPE) AR Lower limbs Neck Axilla ±Back Supra-clavicular Below triceps N Muscle weakness N IR/DM ↑TG N N Hepatic steatosis N Mild dystrophy High CK AD Lower limbs Abd (visc.) IR/DM ↑TG ↓Leptin N N Hepatic steatosis N Acquired Partial Lipodystrophy Subtype Onset ↓Fat ↑Fat Skin Appendages Muscle Bone Mineral Meta-bolic Kidney Nervous GI Liver Spleen GU Endocrine Other n/a n/a Face, trunk, upper limbs, Lower limbs - Muscular appearance - Infrequent IR/ DM ↑ TG - N PCOS Association with diseases Low C3 levels, presence of (C3 linked
Wide cranial sutures Wormian bones stiffness Bulbous fingertips Type B MAD AR <1 year Almost all fat lost None Mottled pigmentation Skin atrophy Alopecia Mandible & clavicle hypoplasia Acroosteolysis contractures Delayed closure of cranial sutures SC calcifications N IR/DM ↑TG N N N Progressive glomerulopathy Dysmorphic facies Progeria Syndrome (BANF1) AR 1-2 years Almost all fat lost None Skin atrophy Pigmented skin lesions Alopecia Severe osteoporosis Osteolysis Micrognathia Scoliosis Dental crowding Open cranial sutures joints Sinus tachycardia Right bundle branch block Pulmonary hypertension N N N N N Growth failure Short stature Atypical Progeria (LMNA) AD de Partial or generalized fat loss None Alopecia Mottled skin pigment Small mandible Dental crowding High arched palate Valvular calcification IR/DM ↑TG N N Mammary hypoplasia Dysmorphic facies Aged appearance Short stature
Normal mechanical fat skin changes Mild clavicular resorption Acroosteolysis Mild flexion contractures Werner syndrome (RECQL2) AR 2nd Limbs skin changes Tissue calcification and ulceration Alopecia Osteoporosis Myocardial infarction IR/DM ↑TG N N N Dysmorphic facies Growth failure Short stature Cataracts ↑Cancer Syndrome (BLM) AR Altered skin pigment Polydactyly DM Mild MR in some patients Reduced fertility Dysmorphic facies Growth failure ↑Cancer PCYT1A AR Limbs Low IR/DM ↑TG Liver steatosis Growth failure Short stature C
MDPL (POLD1) AD de Almost all fat lost ↓ in soles of feet Visc. Skin atrophy Scleroderma Normal hair Hypoplasia of mandible & metatarsals Joint contractures carpal bones Dental crowding Osteoporosis ↓muscle mass N IR/DM ↑TG N Sensori-neural deafness Hypogonadism & cryptorchidism (♂) Hypoplastic breasts(♀) Dysmorphic facies Short stature Cataracts High-pitched voice SHORT (PIK3R1) AD Almost all fat lost (most None Thin, wrinkled skin Delayed dental eruption laxity Micrognathia Heart IR/DM TG Sensori-neural hearing loss Speech N Inguinal hernia Dysmorphic facies Aged appearance IUGR Short stature Glaucoma Rieger anomaly Cataracts Marfan syndrome with neonatal progeroid (FBN1) AD de Birth Almost all fat lost None Alopecia Atrophic skin Arthrogryposis Arachno-dactyly Hyperlaxity fontanels Aortic root dilatation N N Relative N N Dysmorphic facies Aged appearance Myopia
Cockayne syndrome (ERCC6, ERCC8) AR Birth Almost all fat lost None Dry skin Skin atrophy Alopecia Prognathism Long limbs hands/feet Joint contractures Kyphosis Early HTN N Renal disease Microcephaly Severe MR Sensorineural hearing loss Seizures Ataxia Tremor Weakness Dementia N Irregular menses Hypogonadism Dysmorphic facies FTT Short stature Congenital Pigmentary retinopathy Death before 15y Neonatal Progeroid Syndrome AR Birth Face Distal extremities ±gluteal ↓ in palms Alopecia Thin wrinkled skin Hypoplastic nails Phlebomegaly Large fontanels Thin long bones with enlarged metaphyses Loss of teeth Joint contractures ↓muscle mass Prominent scalp veins ↑TG ectasia Macrocephaly MR Hypotonia Truncal ataxia N ↑T4 Irregular menses Dysmorphic facies FTT Short stature Aged appearance Ectropion in childhood syndrome (KCNJ6) AD de Almost all fat lost None Tightly adherent facial skin Joint contractures Scoliosis Micrognathia N N N Microcephaly MR Hypertonia Hyperreflexia Spastic tetraparesis Seizures N N Dysmorphic facies FTT Short stature Aged appearance
syndrome (SPRTN) AR Almost all fat lost None Palmar creases Premature graying of scalp hair Pectus excavatum Sloping shoulders Delayed bone age contractures Kyphoscoliosis Clinodactyly Pes planus ↓ muscle mass Micrognathia N N N N carcinoma N Dysmorphic facies FTT stature Cataracts Sensitivity to genotoxins JMP, CANDLE syndromes (PSMB8) AR Face Feet ± Chest None Erythematous nodular skin lesions Panniculitis Dry, stiff skin Joint contractures Muscle weakness ↓ muscle mass Hypertrophic pulmonary Long and thick fingers Cardiac insufficiency Arrhythmias ↑ TG N MR ± Seizures Basal ganglia calcification enzymes N Dysmorphic facies FTT Short stature Recurrent fever Microcytic anemia ↑ ESR 1 Palms, soles, orbits, scalp, and periarticular regions AD, autosomal dominant; AN, acanthosis nigricans; AR, autosomal recessive; BM, bone marrow fat; CANDLE, chronic neutrophilic dermatosis with lipodystrophy and elevated temperature; DM, diabetes mellitus; ESR, erythrocyte sedimentation rate ; FTT, failure to thrive; HTN, hypertension; IR, insulin resistance; IUGR, intrauterine growth restriction; JMP, joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy; MAD, Mandibuloacral dysplasia; MDPL, mandibular hypoplasia, deafness, progeroid features, and