Abstract Introduction Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by symmetrical, unencapsulated lipomatous masses, most commonly involving the neck and upper trunk. Beyond cosmetic disfigurement, MSL can be associated with systemic complications such as insulin resistance, type 2 diabetes, peripheral neuropathy, and hepatosplenomegaly. In this report, we present a genetically confirmed syndromic MSL case carrying a homozygous pathogenic variant in the Mitofusin-2 (MFN2) gene, consistent with MSL and axonal sensorimotor neuropathy, together with a homozygous variant in the Gonadotropin-Releasing Hormone Receptor (GNRHR) gene, consistent with hypogonadotropic hypogonadism type 7. Clinical Case A 52-year-old male patient with type 2 diabetes diagnosed in 2022 (HbA1c: 7.2%) and treated with oral antidiabetics (linagliptin and pioglitazone) presented with bilateral limb weakness, glove-and-stocking paresthesia, cervical swelling, and inadequately controlled diabetes. His medical history included hepatic steatosis and two prior spinal surgeries for benign lipomatous tumors. Family history revealed paternal consanguinity and a sibling with similar neuromuscular symptoms resulting in immobility. Physical examination showed cervical lipomatosis, parotid gland enlargement, scoliosis, and lower extremity motor deficits and a BMI of 23.9 kg/m². Laboratory results demonstrated insulin resistance (C-peptide: 10.1 μg/L), hypertriglyceridemia (229 mg/dL), hypoalbuminemia, and pancytopenia consistent with hypersplenism. Imaging confirmed hepatosplenomegaly, marked cervical subcutaneous lipomatous infiltration, and peripheral neuropathy. Neck MRI revealed bilateral parathyroid region masses, more prominent on the right side, consistent with lipomatous lesions (right: 45×45 mm; left: 40×35 mm). Genetic testing identified a homozygous pathogenic variant in the MFN2 gene (c.2119CT, p.Arg707Trp), consistent with MSL and axonal sensorimotor neuropathy. Additionally, a homozygous GNRHR variant (c.317AG, p.Gln106Arg) was detected, consistent with hypogonadotropic hypogonadism type 7. Despite normal testosterone levels, the patient had a history of infertility, and relatives reported delayed puberty. The patient is currently treated with linagliptin and pioglitazone for glycemic control, nutritional support, and symptomatic therapy for neuropathy. Metformin was avoided due to the risk of lactic acidosis in mitochondrial dysfunction, and SGLT-2 inhibitors were contraindicated due to prior SGLT-2–induced urticaria. Conclusion This genetically confirmed syndromic form of MSL was associated with insulin resistance, hepatic steatosis, and axonal neuropathy. Early diagnosis, genetic counseling, and multidisciplinary management are essential for the recognition of rare familial lipomatosis disorders. As one of the few reported cases with concurrent MFN2 and GNRHR mutations, this case further expands the genotype–phenotype spectrum of MSL.Figure 1:Neck MRI demonstrating extensive bilateral subcutaneous lipomatous infiltration, more prominent on the right side, with masses in the parathyroid regions (right: 45×45 mm; left: 40×35 mm), consistent with multiple symmetric lipomatosis.
Yavuz et al. (Thu,) studied this question.