IllnessBerardinelli-Seip congenital lipodystrophy, differential diagnosis

NGS +

Congenital generalized lipodystrophy, Berardinelli-Seip syndrome, is characterized by almost complete absence of adipose tissue and a very muscular appearance. Without adipose tissue, the fat is stored in the liver and muscles, leading to serious health problems from birth or early childhood onwards, often with insulin resistance and hence diabetes mellitus. Most affected individuals have also hypertriglyceridemia with eruptive xanthomas, pancreatitis, hepatic steatosis/hepatomegaly and finally liver failure. Some patients develop hypertrophic cardiomyopathy, which can present with heart failure, arrhythmias and cause sudden death. In addition to prominent orbital ridges and large hands/feet, patients have a protruding umbilicus. Females may have clitoromegaly, hirsutism, irregular menstruation and ovarian cysts; many patients develop acanthosis nigricans. Four types of congenital generalized lipodystrophy are differentiated: In addition to the symptoms described, some type 1 affected individuals develop cysts in long bones of the arms/legs after puberty. Type 2 may be associated with mild to moderate mental retardation, and type 3 causes other health problems including poor growth. Type 4 is associated with muscle weakness, developmental delays, joint abnormalities, pyloric stenosis and severe cardiac arrhythmias that can lead to sudden cardiac death. The disease is inherited autosomal recessively. Mutations in the AGPAT2, BSCL2, CAV1 and CAVIN1 genes cause congenital generalized lipodystrophy types 1-4. In some patients no mutations have been found neither in the 4 genes mentioned above nor in the other genes listed as differential diagnostic, even in typical cases. Thus the molecular genetic yield remains currently incomplete.

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

https://doi.org/10.3389/fendo.2020.00039

• Alias: Berardinelli-Seip congenital lipodystrophy
• Alias: Berardinelli-Seip syndrome
• Alias: Brunzell syndrome (AGPAT2)
• Alias: Brunzell syndrome [with bone cysts]
• Alias: Congenital Generalized Lipoatrophy
• Alias: Generalized lipodystrophy
• Alias: Lipodystrophy, congenital generalized
• Alias: Seip syndrome
• Alias: Total lipodystrophy
• Allelic: Acromicric dysplasia (FBN1)
• 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 (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
• Allelic: Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
• Allelic: Epilepsy, progressive myoclonic, 9 (LMNB2)
• Allelic: Gaucher disease, type I-III, IIIC (GBA)
• Allelic: Geleophysic dysplasia 2 (FBN1)
• Allelic: Heart-hand syndrome, Slovenian type (LMNA)
• Allelic: Hutchinson-Gilford progeria (LMNA)
• Allelic: Immunodeficiency 36 (PIK3R1)
• Allelic: Insulin resistance, severe, digenic (PPARG)
• Allelic: Leprechaunism (INSR)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: MASS syndrome (FBN1)
• Allelic: Malouf syndrome (LMNA)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Marfan syndrome (FBN1)
• Allelic: Microcephaly 27, primary, AD (LMNB2)
• Allelic: Neuropathy, distal hereditary motor, type VC (BSCL2)
• Allelic: Obesity, resistance to (PPARG)
• Allelic: Obesity, severe (PPARG)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Allelic: Pulmonary hypertension, primary, 3 (CAV1)
• Allelic: Rabson-Mendenhall syndrome (INSR)
• Allelic: Silver spastic paraplegia syndrome (BSCL2)
• Allelic: Stiff skin syndrome (FBN1)
• Allelic: Weill-Marchesani syndrome 2, dominant (FBN1)
• Autoinflammation, panniculitis + dermatosis syndrome (OTULIN)
• Gaucher disease, perinatal lethal (GBA)
• Hyperinsulinemic hypoglycemia, familial, 5 (INSR)
• Keppen-Lubinsky syndrome (KCNJ6)
• Krabbe disease (GALC)
• Leukodystrophy, hypomyelinating, 7, oligodontia, hypogon. hypogonadism (POLR3A)
• 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 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)
• Restrictive dermopathy, lethal (LMNA)
• Restrictive dermopathy, lethal (ZMPSTE24)
• SHORT s. [Stature; Hyperextensibility/Hernia; Ocular depress. Rieger anom. Teething delay] (PIK3R1)
• Wiedemann-Rautenstrauch syndrome (POLR3A)