Endocrine, nutritional and metabolic diseases
Metabolic disorders
Autosomal recessive
11q12.3
Congenital generalized lipodystrophy (also, Berardinelli-Seip syndrome) is a rare, autosomal recessive syndrome characterized by the almost total absence of subcutaneous adipose tissue in children within the first year of life, resulting in a marked generalized muscular appearance, followed by severe diabetes mellitus, no ketosis/ketonuria, and insulin resistance before adolescence.
| Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|
| 269700.1 | Lebanon | Unknown | Yes | Yes | Lipoatrophy; Generalized muscle hypert... Lipoatrophy; Generalized muscle hypertrophy; Absence of subcutaneous fat  | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Magre et al. 2001 | |
| 269700.2 | Lebanon | Unknown | Yes | Yes | Lipoatrophy ; Generalized muscle hyper... Lipoatrophy ; Generalized muscle hypertrophy; Absence of subcutaneous fat | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Magre et al. 2001 | |
| 269700.3 | Lebanon | Unknown | Yes | Yes | Lipoatrophy ; Generalized muscle hype... Lipoatrophy ; Generalized muscle hypertrophy; Absence of subcutaneous fat | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Magre et al. 2001 | |
| 269700.4 | Lebanon | Unknown | Yes | Yes | Lipoatrophy ; Generalized muscle hyp... Lipoatrophy ; Generalized muscle hypertrophy; Absence of subcutaneous fat | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Magre et al. 2001 | |
| 269700.5 | Lebanon | Unknown | Yes | Yes | Lipoatrophy ; Generalized muscle hyp... Lipoatrophy ; Generalized muscle hypertrophy; Absence of subcutaneous fat | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Magre et al. 2001 | |
| 269700.6 | Lebanon | Male | Yes | Diabetes mellitus; Cardiomyopathy; Dec... Diabetes mellitus; Cardiomyopathy; Decreased serum leptin; Reduced subcutaneous adipose tissue; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Agarwal et al. 2003 | ||
| 269700.7.1 | Lebanon | Male | Yes | Yes | Decreased serum leptin; Reduced subcuta... Decreased serum leptin; Reduced subcutaneous adipose tissue; Intellectual disability ; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Agarwal et al. 2003 | First cousin once re... |
| 269700.7.2 | Lebanon | Female | Yes | Yes | Decreased serum leptin; Reduced subcu... Decreased serum leptin; Reduced subcutaneous adipose tissue; Cardiomyopathy; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Agarwal et al. 2003 | Sibling of 269700.7.... |
| 269700.7.3 | Lebanon | Male | Yes | Yes | Decreased serum leptin; Reduced subcu... Decreased serum leptin; Reduced subcutaneous adipose tissue; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Agarwal et al. 2003 | Sibling of 269700.7.... |
| 269700.8 | Lebanon | Male | Diabetes mellitus; Cardiomyopathy; Dec... Diabetes mellitus; Cardiomyopathy; Decreased serum leptin; Reduced subcutaneous adipose tissue; Intellectual Disability; ; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Agarwal et al. 2003 | |||
| 269700.9 | Lebanon | Male | Diabetes mellitus; Cardiomyopathy; D... Diabetes mellitus; Cardiomyopathy; Decreased serum leptin; Reduced subcutaneous adipose tissue; Intellectual Disability; Cardiomyopathy; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Agarwal et al. 2003 | |||
| 269700.10 | Oman | Female | Yes | Generalized muscle hypertrophy; Lipodys... Generalized muscle hypertrophy; Lipodystrophy; Acanthosis nigricans; Insulin resistance; | NM_001122955.3:c.969G>A | Homozygous | Autosomal, Recessive | Heathcote et al. 2002 | ||
| 269700.11 | Oman | Female | Yes | Generalized muscle hypertrophy; Lipody... Generalized muscle hypertrophy; Lipodystrophy; Acanthosis nigricans; Insulin resistance; | NM_001122955.3:c.969G>A | Homozygous | Autosomal, Recessive | Heathcote et al. 2002 | ||
| 269700.12 | Oman | Female | Yes | Generalized muscle hypertrophy; Lipo... Generalized muscle hypertrophy; Lipodystrophy; Acanthosis nigricans; Insulin resistance; | NM_001122955.3:c.864-2A>C | Homozygous | Autosomal, Recessive | Heathcote et al. 2002 | ||
| 269700.G.1 | Lebanon | Lipoatrophy; Hyperlipidemia; Hepatom... Lipoatrophy; Hyperlipidemia; Hepatomegaly; Insulin resistance; | NM_001122955.3:c.509_513delATCGT | Homozygous | Autosomal, Recessive | Van Maldergem et al. 2002 | Group of 21 patients... |
Raygada and Rennert (2005) described an affected sib pair born to consangunoeus healthy parents. One maternal first cousin had been earlier diagnosed with the condiiton. Both children were born with paucity of fat, protruding abdomen, and acromegaloid features. Both brother and sister showed signs of precocious puberty, which developed earlier in the female patient. Intellectual disability was more prnonounced in the male sibling.
Agarwal et al. (2003) analyzed a consanguineous family from Palestine with a daughter affected with congenital generalized lipodystrophy. Genotyping showed no substantial alterations in the coding regions of the BSCL2 and AGPAT2 genes, indicating that a mutation in a yet unmapped gene resulted in the observed phenotype.