A Novel Generalized Lipodystrophy-Associated Progeroid Syndrome Due to Recurrent Heterozygous LMNA p.T10I Mutation

Area of Science:

• Genetics and Molecular Biology
• Endocrinology
• Cardiology

Background:

• Mutations in the Lamin A/C (LMNA) gene cause various progeroid disorders.
• A recurrent de novo heterozygous LMNA p.T10I mutation was identified in patients with atypical progeroid syndrome (APS).
• This mutation suggests a distinct progeroid syndrome characterized by generalized lipodystrophy.

Observation:

• Nine new patients and two previously reported patients with the LMNA p.T10I mutation were studied.
• Clinical and metabolic features were compared to other APS patients.
• Key features included mottled skin, joint contractures, and cardiomyopathy.

Findings:

• Patients with LMNA p.T10I mutation showed increased prevalence of generalized lipodystrophy, diabetes mellitus, acanthosis nigricans, hypertriglyceridemia, and hepatomegaly.
• Fasting insulin and triglyceride levels were higher, while leptin and HDL cholesterol were lower.
• Three patients required cardiac transplants due to cardiomyopathy.

Implications:

• The LMNA p.T10I mutation defines a distinct syndrome, generalized lipodystrophy-associated progeroid syndrome.
• This syndrome presents unique clinical and metabolic challenges compared to other progeroid conditions.
• Multisystem assessment and regular evaluations are vital for managing hyperglycemia, hypertriglyceridemia, hepatic steatosis, and cardiomyopathy.