[MIM 608 594, 269 700]

(Berardinelli-Seip-Lawrence syndrome; Lawrence-Seip syndrome syndrome; Seip syndrome, lipodystrophy-acromegaloid gigantism , lipodystrophy type Berardinelli, BSCL acronym of Berardinelli-Seip Congenital Lipodystrophy, congenital generalized lipodystrophy)

Extremely rare: prevalence estimated at 0.2/100,000. Transmission: autosomal recessive. 

Different types:

-         type 1 (BSCL1):  mutations of the AGPAT2 gene (9q34) which encodes 1-acylglycerol-3-phosphate-acyltransferase: most frequent in North Africa and sub-Saharan countries, and in West Indies (Antilles)

-         type 2 (BSCL2): mutations of the gene encoding seipin (11q13) responsible for the transformation of pre-adipocytes into adipocytes: this form is more severe and often associated with intellectual deficit. More frequent in Lebanon, Portugal, Brazil, Turkey and Japan

-        type 3 (very rare): mutations of the CAV1 gene (7q31) coding for caveoline 1: that protein is part of the cellular membrane and present in adipocytes, fibroblasts and endothelial cells

-        type 4 (very rare): mutations of the PTRF or CAVIN1 gene (17q21.2) [MIM 613 327] coding for the cytoplasmic protein cavin-1 which combines with caveolin 3; association of congenital lipodystrophy with muscular dystrophy (exercise-inducd myalgia, muscle rippling following its percussion, elevated CK level) and heart rhythm disorders (supraventricular tachycardia, long QT, Wolff-Parkinson-White) with a significant risk of sudden death (non-compaction of the left ventricle); hypertrophy of some smooth muscles, rigidity of the spine with hyperlordosis, (see also: Rippling muscle disease)

Lipoatrophy is widespread, present from birth, and associated with insulin resistance. Subcutaneous and visceral adipose tissue is absent from birth and fat accumulates in ectopic tissues such as the liver.

Insulin resistance causes important anabolism with:

-         an acromegalic (macroglossia) phenotype with an athletic look (muscle hypertrophy) and accelerated growth; organomegaly

-         high blood pressure and risk of hypertrophic cardiomyopathy (BSCL 2); coronary artery disease (cause of death)

-         abundant hair and hypertrichosis

-         hepatomegaly with steatosis, risk of cirrhosis with splenomegaly, esophageal varices

-         hypertriglyceridemia with risk of pancreatitis

-         acanthosis nigricans: brown or black skin lesions, at the level of flexor areas (neck, axilla, groin)

-         rounded bone defects in the epiphyses of long bones during childhood and adolescence

-         mental retardation in about 50 % of cases (BSCL2)

Treatment: caloric restriction, insulin, hypolipidemic drugs.

Anesthetic implications: 

Management of insulinotherapy and of the cardiovascular risk (hypertension, angina). Monitoring of BP, ECG, echocardiography (types 2 and 4). Check liver function.

Macroglossia and tonsillar hypertrophy can cause upper airway obstruction and obstructive sleep apnea. In case of hypertriglyceridemia, it is better to avoid TIVA with propofol : risk of acute pancreatitis.

A case of delayed wake-up after a 70 minutes anesthesia with sevoflurane has been reported. In another case of lipodystrophy, it has been shown that delayed wake-up (and onset of anesthesia) was directly linked to the increase in solubility of sevoflurane in relation with hyperlipidemia. In case of type 4, it is probably wise to avoid the halogenated agents and tsuccinylcholine.

References : 

• Capeau J, Magré L, Lascols O, Caron M, Béréziat V, Vigouroux C. 
  Lipodystrophies primitives. 
  Encyclopédie Orphanet février 2007
• Bustamante SE, Appachi E. 
  Acute pancreatitis after anesthesia with propofol in a child with glycogen storage disease type IA. 
  Pediatr Anesth 2006; 16: 680-3.
• Bennett T, Allford M. 
  Delayed emergence from anesthesia in a child with congenital generalized lipodystrophy (Berardinelli-Seip syndrome). 
  Pediatr Anesth 2012; 22: 299-300.
• Steen ER, De Baerdemaeker LEC, Van Limmen E, Wouters P. 
  Some pharmacokinetics of sevoflurane in a child with severe lipodystrophy. 
  A & A Case Reports 2014; 2: 61-4. 
• Gomes Lima J, Ferreira dos Santos MC , Araujo de Melo Campos JT. 
  Congenital generalized lipodystrophy.
  J Rare Dis Res Treat 2018 ; 3 : 1-6.
• Magalhaes-Montenegro R, Oliveira-Fernandez V, Penaforte Saboia JG, Dias Rangel Montenegro AP et al.
  Type 2 congenital generalized lipodystrophy : the diagnosis is in your hands.
  J Pediatrics 2019 ; 207 : 257
• Al Aamri I, Nagathan SD, Al-Abri IA, Al Murshedi FM, Maddali MM.
  Child with Congenital Generalized Lipodystrophy Type 4 for electrophysiology study and catheter ablation: anesthetic challenges.
  J  Cardiothor Vasc Anesth 2022 ; 36 : 4228-9
  
  

Updated: January 2023