Fertility and obstetrical complications in women with LMNA-related familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy due to LMNA (lamin A/C) mutations is a rare disorder characterized by a selective loss of adipose tissue and insulin resistance. Dyslipidemia and severe diabetes often occur during its evolution. Only isolated and contradictory case reports have been published on the obstetrical prognosis in lipodystrophy. The aim of our study was to compare the fertility and occurrence of obstetrical complications of women with familial partial lipodystrophy due to LMNA (lamin A/C) mutations with those of nonaffected relatives, women from the general population, and women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: Data were obtained from clinical follow-up of seven families with patients exhibiting mutations in LMNA (five R482W, one R482Q, one R439C) (14 affected among 48 women). RESULTS: The mean number of live children per woman was 1.7 in affected patients vs. 2.8 in nonaffected relatives. Fifty-four percent of LMNA-mutated women exhibited a clinical phenotype of PCOS, 28% suffered from infertility, 50% experienced at least one miscarriage, 36% developed gestational diabetes, and 14% experienced eclampsia and fetal death. Mean blood leptin level was significantly lower in LMNA-mutated patients than in nonaffected relatives (5.0 +/- 3.8 ng/ml vs 14.3 +/- 3.6; P < 0.001) despite similar body mass index (21.0 +/- 4.2 vs 22.4 +/- 2.2; P = 0.49). CONCLUSION: In these LMNA-linked lipodystrophic patients, the prevalence of PCOS, infertility, and gestational diabetes was higher than in the general population. Moreover, the prevalence of gestational diabetes and miscarriages was higher in lipodystrophic LMNA-mutated women than previously reported in PCOS women with similar body mass index. Women with lipodystrophies due to LMNA mutations are at high risk of infertility, gestational diabetes, and obstetrical complications and require reinforced gynecological and obstetrical care.

[Monogenic severe insulin resistance syndromes]. / Syndromes d'insulinorésistance extrême génétiquement déterminés.

PURPOSE: To make a point about monogenic insulin resistance syndromes. CURRENT KNOWLEDGE AND KEY POINTS: Extreme insulin resistance syndromes are rare entities. The clinical and biological presentation is similar to that one of metabolic syndrome. Polycystic ovaries syndrome, non-alcoholic liver steatosis, acanthosis nigricans and overall, lipo-atrophic syndrome must be sought. Genetically determined forms are mainly linked to mutations of the insulin receptor gene and to lipoatrophic syndrome-linked mutations. The three syndromes related to mutations of the insulin receptor gene are Type A syndrome, first described by Kahn in young women, whereas leprechaunism and Rabson-Mendenhall syndromes are of neonatal onset. Main insulin resistance syndromes associated with lipo-atrophy are 1) Berardinelli-Seip or congenital generalized lipo-atrophic syndrome linked to mutations of seipin or AGPAT2 gene, 2) Dunnigan or partial familial lipoatrophic syndrome linked to mutations of lamin A/C, or sometimes PPAR gamma gene, and 3) acro-mandibular dysplasia and Köbberling syndrome. FUTURE PROSPECTS AND PROJECTS: In conclusion, an early onset of insulin resistance, especially in association with lipodystrophy must suggest a monogenic insulin resistance syndrome. Outstanding advances in insulin resistance pheno- and genotype identification, despite incomplete yet, offers a better understanding of insulin resistance, atherosclerosis and ageing mechanisms, that should lead to therapeutic improvement.