IllnessLipodystrophy, familial; differential diagnosis

NGS +

[Sanger]

Congenital generalized lipodystrophy (Berardinelli-Seip) is rare and characterized by almost complete lack of adipose tissue. It belongs to a group of related disorders showing loss of adipose tissue. Symptoms usually present early and include insulin resistance that can develop into diabetes mellitus, hypertriglyceridemia (with eruptive xanthomas and pancreatitis), hepatic steatosis, hepatomegaly, liver failure and hypertrophic cardiomyopathy. In females, clitoromegaly, hirsutism, irregular menstruation and cystic ovaries may be prominent. Many patients develop acanthosis nigricans. There are several genetic types of congenital generalized lipodystrophy: type 1 patients develop cysts in the long limb bones after puberty. Type 2 may be associated with mental retardation. Type 3 appears to impair growth. Type 4 is associated with muscle weakness, delayed development, joint abnormalities, pyloric stenosis, and severe cardiac arrhythmias. Inheritance is either autosomal dominant or autosomal recessive. DNA yield in Berardinelli-Seip congenital lipodystrophy is very high; however overall, the molecular genetic yield in lipodstrophies is unknown and low, it can be increased by next-generation sequencing analysis of the many known lipodystrophy-associated genes.

References: https://www.ncbi.nlm.nih.gov/books/NBK1212/

https://www.ncbi.nlm.nih.gov/books/NBK201365/

https://www.ncbi.nlm.nih.gov/books/NBK1307/

• Alias: Berardinelli-Seip congenital lipodystrophy, BSCL
• Alias: Insulin-Resistenz incl. Lipodystrophie
• Allelic: Agammaglobulinemia 7, AR (PIK3R1)
• Allelic: Cardiomyopathy, dilated, 1A (LMNA)
• Allelic: Carotid intimal medial thickness 1 (PPARG)
• Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Allelic: Colorectal cancer, susceptibility to, 10 (POLD1)
• Allelic: Diabetes mellitus, insulin-resistant, with acanthosis nigricans (INSR)
• Allelic: Diabetes, type 2 (PPARG)
• Allelic: Ectopia lentis, familial (FBN1)
• Allelic: Emery-Dreifuss muscular dystrophy 2, AD; 3, AR (LMNA)
• Allelic: Encephalopathy, progressive, with or without lipodystrophy (BSCL2)
• Allelic: Epilepsy, progressive myoclonic, 9 (LMNB2)
• Allelic: Heart-hand syndrome, Slovenian type (LMNA)
• Allelic: Hutchinson-Gilford progeria (LMNA)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 5 (INSR)
• Allelic: Immunodeficiency 36 (PIK3R1)
• Allelic: Insulin resistance, severe, digenic (PPARG)
• Allelic: Leukodystrophy, hypomyelin., 7, with/-out oligodontia, hypogonadotr. hypogonadism (POLR3A)
• Allelic: MASS syndrome (FBN1)
• Allelic: Malouf syndrome (LMNA)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Marfan syndrome (FBN1)
• Allelic: Muscular dystrophy, congenital (LMNA)
• Allelic: Neuropathy, distal hereditary motor, type VA (BSCL2)
• Allelic: Obesity, resistance to (PPARG)
• Allelic: Obesity, severe (PPARG)
• Allelic: Pulmonary hypertension, primary, 3 (CAV1)
• Allelic: Restrictive dermopathy, lethal (LMNA)
• Allelic: Restrictive dermopathy, lethal (ZMPSTE24)
• Allelic: Silver spastic paraplegia syndrome (BSCL2)
• Allelic: Weill-Marchesani syndrome 2, AD (FBN1)
• Acromicric dysplasia (FBN1)
• Allelic: Gaucher disease, perinatal lethal (GBA1)
• Allelic: Gaucher disease, type I, III, IIIC (GBA1)
• Allelic: Lewy body dementia, susceptibility to (GBA1)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA1)
• Autoinflammation, panniculitis + dermatosis syndrome (OTULIN)
• Berardinelli-Seip congenital lipodystrophy (AGPAT2)
• Diabetes mellitus, type II (AKT2)
• Gaucher disease, type II (GBA1)
• Geleophysic dysplasia 2 (FBN1)
• Hypoinsulinemic hypoglycemia with hemihypertrophy (AKT2)
• Keppen-Lubinsky syndrome (KCNJ6)
• Krabbe disease (GALC)
• Leprechaunism (INSR)
• Lipodystrophy, congenital generalized, type 1 (AGPAT2)
• Lipodystrophy, congenital generalized, type 2 (BSCL2)
• Lipodystrophy, congenital generalized, type 3 (CAV1)
• Lipodystrophy, congenital generalized, type 4 (CAVIN1)
• Lipodystrophy, familial partial, type 2 (LMNA)
• Lipodystrophy, familial partial, type 3 (PPARG)
• Lipodystrophy, familial partial, type 4 (PLIN1)
• Lipodystrophy, familial partial, type 5 (CIDEC)
• Lipodystrophy, familial partial, type 6 (LIPE)
• Lipodystrophy, familial partial, type 7 (CAV1)
• Lipodystrophy, partial, acquired, susceptibility to (LMNB2)
• Mandibular hypoplasia, deafness, progeroid features + lipodystrophy syndrome (POLD1)
• Mandibuloacral dysplasia progeroid syndrome (MTX2)
• Mandibuloacral dysplasia with type B lipodystrophy (ZMPSTE24)
• Marfan lipodystrophy syndrome (FBN1)
• Microcephalic osteodysplastic primordial dwarfism, type II (PCNT)
• Nestor-Guillermo progeria syndrome (BANF1)
• Proteasome-associated autoinflammatory syndrome 1 + digenic forms (PSMB8)
• Ruijs-Aalfs syndrome (SPRTN)
• SHORT syndrome [Partial lipodystrophy, Rieger anomaly, short sture] (PIK3R1)
• Spondylometaphyseal dysplasia with cone-rod dystrophy (PCYT1A)
• Stiff skin syndrome (FBN1)
• Wiedemann-Rautenstrauch syndrome (POLR3A)