Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Berardinelli-Seip congenital lipodystrophy

Reviewed August 2008

What is Berardinelli-Seip congenital lipodystrophy?

Berardinelli-Seip congenital lipodystrophy is a rare condition characterized by a lack of fatty (adipose) tissue in the body. This lack of adipose tissue means that fats must be stored elsewhere in the body, such as in the liver and muscles. The abnormal handling and storage of fats leads to serious medical problems.

The signs and symptoms of Berardinelli-Seip congenital lipodystrophy are apparent from birth or early infancy. Common features of this disorder include high levels of fats (triglycerides) circulating in the bloodstream (hypertriglyceridemia) and insulin resistance, a condition in which the body's tissues are unable to recognize insulin. Insulin is a hormone that helps regulate blood sugar levels. During adolescence, insulin resistance may develop into a more serious disease called diabetes mellitus. Berardinelli-Seip congenital lipodystrophy also causes an abnormal buildup of fats in the liver (hepatic steatosis), which can damage this organ. An accumulation of fats in the heart can cause a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and sudden death.

People with Berardinelli-Seip congenital lipodystrophy have a distinctive physical appearance. The combination of an almost total absence of adipose tissue and an overgrowth of muscle tissue makes these individuals appear very muscular. They also tend to have a large chin, prominent bones above the eyes (orbital ridges), and large hands and feet. Affected females may have an enlarged clitoris (clitoromegaly), and males also tend to have enlarged external genitalia. Many people with this disorder develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.

Researchers have described two similar forms of Berardinelli-Seip congenital lipodystrophy, type 1 and type 2, which are distinguished by their genetic cause. The two types also have a few differences in their typical signs and symptoms. For example, in addition to the features described above, some people with type 1 develop bone cysts in the long bones of the arms and legs after puberty. Type 2 is frequently associated with intellectual disability, which is usually mild to moderate. Intellectual disability is occasionally seen with type 1, although it is much less common.

How common is Berardinelli-Seip congenital lipodystrophy?

Berardinelli-Seip congenital lipodystrophy has an estimated prevalence of 1 in 10 million people worldwide. Although this condition has been reported in populations around the world, it may be more common in certain regions of Lebanon, Brazil, and Portugal.

What genes are related to Berardinelli-Seip congenital lipodystrophy?

Mutations in the AGPAT2 and BSCL2 genes cause the two types of Berardinelli-Seip congenital lipodystrophy. AGPAT2 mutations are responsible for type 1, while mutations in BSCL2 cause type 2.

The proteins produced from the AGPAT2 and BSCL2 genes play important roles in adipocytes, which are the fat-storing cells in adipose tissue. Mutations in either of these genes disrupt the normal development or function of adipocytes, preventing normal adipose tissue from forming. As a result, the body is unable to use and store fats properly. An almost total absence of body fat underlies the varied signs and symptoms of Berardinelli-Seip congenital lipodystrophy.

The protein produced from the BSCL2 gene is also present in the brain and testes, although its function in these tissues is unknown. A loss of this protein in the brain may help explain why many people with Berardinelli-Seip congenital lipodystrophy type 2 have intellectual disability.

In some people with Berardinelli-Seip congenital lipodystrophy, no mutation in the AGPAT2 or BSCL2 gene has been found. Researchers are searching for additional genetic changes that may cause this disorder.

Related Gene(s)

Changes in these genes are associated with Berardinelli-Seip congenital lipodystrophy.

  • AGPAT2
  • BSCL2

How do people inherit Berardinelli-Seip congenital lipodystrophy?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Berardinelli-Seip congenital lipodystrophy?

These resources address the diagnosis or management of Berardinelli-Seip congenital lipodystrophy and may include treatment providers.

  • Gene Review: Berardinelli-Seip Congenital Lipodystrophy (http://www.ncbi.nlm.nih.gov/books/NBK1212)
  • Genetic Testing Registry: Berardinelli-Seip congenital lipodystrophy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0221032)
  • Genetic Testing Registry: Congenital generalized lipodystrophy type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1720862)
  • Genetic Testing Registry: Congenital generalized lipodystrophy type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1720863)
  • Lipodystrophy.info at the University of Texas Southwestern Medical Center (http://www.utsouthwestern.edu/education/medical-school/departments/internal-medicine/divisions/nutrition/lipodystrophy/index.html)
  • MedlinePlus Encyclopedia: Hypertrophic Cardiomypathy (http://www.nlm.nih.gov/medlineplus/ency/article/000192.htm)

You might also find information on the diagnosis or management of Berardinelli-Seip congenital lipodystrophy in Educational resources (http://www.ghr.nlm.nih.gov/condition/berardinelli-seip-congenital-lipodystrophy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/berardinelli-seip-congenital-lipodystrophy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Berardinelli-Seip congenital lipodystrophy?

You may find the following resources about Berardinelli-Seip congenital lipodystrophy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Berardinelli-Seip congenital lipodystrophy?

  • Berardinelli-Seip syndrome
  • Brunzell syndrome (with bone cysts)
  • BSCL
  • congenital generalized lipodystrophy
  • generalized lipodystrophy
  • lipodystrophy, congenital generalized
  • Seip syndrome
  • total lipodystrophy

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Berardinelli-Seip congenital lipodystrophy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Berardinelli-Seip congenital lipodystrophy?

acanthosis nigricans ; adipocytes ; adipose tissue ; autosomal ; autosomal recessive ; cardiomyopathy ; cell ; cirrhosis ; congenital ; cysts ; diabetes ; diabetes mellitus ; disability ; gene ; genitalia ; heart failure ; hepatic ; hormone ; hypertriglyceridemia ; hypertrophic ; inherited ; insulin ; insulin resistance ; lipodystrophy ; mutation ; prevalence ; protein ; puberty ; recessive ; syndrome ; testes ; tissue ; triglycerides

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Agarwal AK, Arioglu E, De Almeida S, Akkoc N, Taylor SI, Bowcock AM, Barnes RI, Garg A. AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat Genet. 2002 May;31(1):21-3. Epub 2002 Apr 22. (http://www.ncbi.nlm.nih.gov/pubmed/11967537?dopt=Abstract)
  • Agarwal AK, Barnes RI, Garg A. Genetic basis of congenital generalized lipodystrophy. Int J Obes Relat Metab Disord. 2004 Feb;28(2):336-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14557833?dopt=Abstract)
  • Agarwal AK, Garg A. Genetic basis of lipodystrophies and management of metabolic complications. Annu Rev Med. 2006;57:297-311. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16409151?dopt=Abstract)
  • Agarwal AK, Garg A. Genetic disorders of adipose tissue development, differentiation, and death. Annu Rev Genomics Hum Genet. 2006;7:175-99. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16722806?dopt=Abstract)
  • Agarwal AK, Simha V, Oral EA, Moran SA, Gorden P, O'Rahilly S, Zaidi Z, Gurakan F, Arslanian SA, Klar A, Ricker A, White NH, Bindl L, Herbst K, Kennel K, Patel SB, Al-Gazali L, Garg A. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J Clin Endocrinol Metab. 2003 Oct;88(10):4840-7. (http://www.ncbi.nlm.nih.gov/pubmed/14557463?dopt=Abstract)
  • Fu M, Kazlauskaite R, Baracho Mde F, Santos MG, Brandão-Neto J, Villares S, Celi FS, Wajchenberg BL, Shuldiner AR. Mutations in Gng3lg and AGPAT2 in Berardinelli-Seip congenital lipodystrophy and Brunzell syndrome: phenotype variability suggests important modifier effects. J Clin Endocrinol Metab. 2004 Jun;89(6):2916-22. (http://www.ncbi.nlm.nih.gov/pubmed/15181077?dopt=Abstract)
  • Gene Review: Berardinelli-Seip Congenital Lipodystrophy (http://www.ncbi.nlm.nih.gov/books/NBK1212)
  • Magré J, Delépine M, Khallouf E, Gedde-Dahl T Jr, Van Maldergem L, Sobel E, Papp J, Meier M, Mégarbané A, Bachy A, Verloes A, d'Abronzo FH, Seemanova E, Assan R, Baudic N, Bourut C, Czernichow P, Huet F, Grigorescu F, de Kerdanet M, Lacombe D, Labrune P, Lanza M, Loret H, Matsuda F, Navarro J, Nivelon-Chevalier A, Polak M, Robert JJ, Tric P, Tubiana-Rufi N, Vigouroux C, Weissenbach J, Savasta S, Maassen JA, Trygstad O, Bogalho P, Freitas P, Medina JL, Bonnicci F, Joffe BI, Loyson G, Panz VR, Raal FJ, O'Rahilly S, Stephenson T, Kahn CR, Lathrop M, Capeau J; BSCL Working Group. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet. 2001 Aug;28(4):365-70. (http://www.ncbi.nlm.nih.gov/pubmed/11479539?dopt=Abstract)
  • Van Maldergem L, Magré J, Khallouf TE, Gedde-Dahl T Jr, Delépine M, Trygstad O, Seemanova E, Stephenson T, Albott CS, Bonnici F, Panz VR, Medina JL, Bogalho P, Huet F, Savasta S, Verloes A, Robert JJ, Loret H, De Kerdanet M, Tubiana-Rufi N, Mégarbané A, Maassen J, Polak M, Lacombe D, Kahn CR, Silveira EL, D'Abronzo FH, Grigorescu F, Lathrop M, Capeau J, O'Rahilly S. Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. J Med Genet. 2002 Oct;39(10):722-33. Erratum in: J Med Genet. 2003 Feb;40(2):150.. (http://www.ncbi.nlm.nih.gov/pubmed/12362029?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2008
Published: December 16, 2014