familial partial lipodystrophy, Dunnigan type

Familial partial lipodystrophy, Dunnigan type is a rare inherited disorder that affects the distribution of body fat and is characterized by loss of subcutaneous fat in the limbs and trunk with relative accumulation in the face, neck, axillary, and pelvic regions. It is associated with metabolic complications such as insulin resistance, diabetes mellitus, dyslipidemia, and liver steatosis. Pathogenic variants in the LMNA gene underlie this condition, which follows an autosomal dominant pattern of inheritance. Although precise prevalence data are not available, the condition is recognized as an uncommon but significant genetic disorder.

Individuals with familial partial lipodystrophy, Dunnigan type exhibit a distinctive pattern of fat loss, with marked loss of subcutaneous adipose tissue in the limbs and truncal areas while developing increased fat deposition in the face and neck. Muscular hypertrophy is commonly observed and many patients experience myopathy and exercise-induced myalgia. Metabolic abnormalities appear early and include insulin resistance, glucose intolerance, and insulin-resistant diabetes mellitus, accompanied by features such as hyperglycemia, dyslipidemia, and hepatic steatosis. Other characteristic findings include hepatomegaly, splenomegaly, and constrictive median neuropathy. Not all individuals experience every feature and severity varies considerably.

This condition is caused by pathogenic variants in the LMNA gene, which encodes proteins that play a key role in maintaining the structure of the cell nucleus. Disruption of LMNA function leads to abnormal fat distribution and contributes to metabolic complications. Familial partial lipodystrophy, Dunnigan type is inherited in an autosomal dominant manner, meaning that a single copy of the altered gene can cause the condition, and it can be passed from an affected parent to approximately half of their children. Genetic counseling is recommended for families to understand the implications of this inheritance pattern and for guidance with family planning.

Currently, management of familial partial lipodystrophy, Dunnigan type focuses on supportive care and symptom management rather than a specific curative treatment. Treatment is tailored to the individual and typically involves a multidisciplinary team to address metabolic complications and musculoskeletal concerns. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients should discuss treatment options with their healthcare team, and genetic counseling is advised to help families navigate the implications of this inherited condition.

The long-term outlook for individuals with familial partial lipodystrophy, Dunnigan type varies depending on the severity of metabolic complications and other clinical features. With current standards of care and ongoing advances in medical management, many individuals can lead productive lives into adulthood although careful management of insulin resistance, dyslipidemia, and liver health remains critical. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to seek genetic counseling and connect with specialists experienced in managing metabolic and musculoskeletal complications. That severity and symptoms vary widely between individuals.