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Multiple symmetric lipomatosis (MSL) primarily affects men and has a sex ratio of 15:1 to 30:1, depending on the region. The disorder may occur in all ethnic groups. Prevalence and incidence are not known but estimates are available for certain countries (e.g. prevalence for males in Italy 1/25,000). More than 300 cases have been reported.

MSL generally occurs in mid- to late-adulthood (30-60 years of age), but cases in childhood, adolescence and in elderly have also been reported. The course of the disease is characterized by rapid early development, followed by slow progressive growth of adipose deposits in and around the face, neck, occipital region, supraclavicular fossa, and shoulder areas. The thighs may be affected. Patients often initially present to medical attention for esthetic reasons and/or difficulties when dressing. Over time, neck muscles may become compressed, reducing the size of the trachea and esophagus with associated respiratory obstruction and obstructive sleep apnea. Patients also often have polyneuropathy, liver disease, and metabolic syndrome with abnormal glucose tolerance, and hyperlipidemia. Most affected patients are obese but some rare cases (10%) show a normal body weight. Malignant transformation into liposarcoma has been reported in very rare cases. MSL can also be associated with partial lipodystrophy and myopathy.

The pathogenesis of MSL is not fully understood, but it may be related to defective noradrenergic regulation of mitochondria in brown fat. The disease is strongly associated with alcohol abuse (up to 90% of patients). Rare genetic forms have also been described, generally occurring earlier in a familial form. Disease-causing mutations have been reported in MFN2 (1p36.22) and LIPE (19q13.2) genes, encoding the mitofusin 2 and the hormone sensitive lipase, respectively.

Diagnosis of MSL may be complicated because of confusion with obesity. Clinical findings showing a specific distribution of adipose tissue are diagnostic (specifically, sparing of the distal arms and legs), as is alcohol abuse. Nevertheless, a family history of MSL should be searched. Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) can confirm the presence of symmetrical, non-encapsulated fat deposits. Biopsy of fatty masses can also be used to rule out liposarcoma. Dyslipidemia, insulin resistance and diabetes should also be investigated.

Obesity and liposarcoma are the main differential diagnoses. Other disorders to consider include Cushing syndrome, familial partial lipodystrophy, especially Dunnigan syndrome related to LMNA gene mutations, familial angiolipomatosis, Prune belly syndrome and lymphoma.

A mitochondrial and autosomal recessive inheritance have been reported. MSL can also be transmitted following an autosomal dominant mode of inheritance.

In some patients, treatment may not be required. When treatment is needed for esthetic reasons, or due to sleep apnea, aerodigestive tract compression, or severe pain, it generally involves surgery such as lipectomy, liposuction (or ultrasound-assisted liposuction). Cessation of alcohol intake is recommended but generally not associated with a decrease of lipomatosis. Weight loss may help in halting progression in some cases. The treatment of associated morbidities (diabetes, cirrhosis) is required. Screening for alcohol- (and often tobacco-) associated cancers is useful.

MSL is basically a benign condition but in some cases, there may be serious physical, cosmetic and psychological repercussions. Associated disorders may affect the prognosis. Alcoholism plays a greater role in morbidity and mortality than MSL itself.