Multiple Symmetric Lipomatosis: Symptoms, Types, Causes and Treatment

Multiple Symmetric Lipomatosis (MSL), also known as Madelung’s disease or Launois–Bensaude syndrome, is a rare disorder characterized by abnormal, symmetric fat deposits in specific regions of the body. Despite being recognized for over a century, its causes, clinical manifestations, and optimal management strategies remain areas of active investigation. This article synthesizes the latest research to provide a comprehensive overview of MSL, focusing on its symptoms, classification types, underlying causes, and available treatments.

Symptoms of Multiple Symmetric Lipomatosis

MSL presents with a variety of symptoms, ranging from cosmetic concerns to significant functional impairments. Recognizing these features is essential for timely diagnosis and appropriate management.

Symptom	Description	Frequency/Impact	Source(s)
Fatty Masses	Symmetric, nonencapsulated fat deposits	Most common, hallmark sign	1 2 3 4 6
Distribution	Neck, shoulders, upper trunk, arms, face	Classical locations	1 2 3 4 6 8
Neurologic Signs	Peripheral neuropathy, sensorimotor polyneuropathy	High prevalence, functional impact	1 2 7 9 12
Compression	Airway/esophagus compression, dyspnea, dysphagia	Can be life-threatening if severe	3 5 12
Metabolic Issues	Hyperlipidemia, glucose intolerance	Frequently associated comorbidities	2 12 8
Cosmetic Issues	Disfigurement, psychological distress	Common reason for seeking treatment	3 4 6 15

Table 1: Key Symptoms

Fat Distribution and Growth Patterns

The signature symptom of MSL is the development of multiple, symmetric, nonencapsulated fat masses. These typically appear on the neck, shoulders, upper trunk, arms, and sometimes the face. The growth of these fatty deposits is usually slow and progressive, often spanning several years before diagnosis. The masses are generally painless but can become conspicuous and disfiguring, leading many patients to seek medical help for cosmetic reasons 1 2 3 4 6.

Neurological Involvement

A substantial proportion of MSL patients experience neurological symptoms—most commonly, peripheral neuropathy. This can present as numbness, tingling, weakness, or even sensorimotor polyneuropathy, which affects both movement and sensation. Central nervous system involvement, such as myoclonus or cerebellar ataxia, though less common, has also been documented 1 2 7 9 12.

Compression Symptoms

As the fatty masses enlarge, they may compress adjacent structures, causing symptoms such as dyspnea (difficulty breathing), dysphagia (difficulty swallowing), or even airway obstruction. In rare cases, this necessitates urgent interventions like tracheostomy to maintain the airway 3 5 12.

Metabolic and Systemic Features

MSL is frequently associated with metabolic abnormalities, including hyperlipidemia and impaired glucose tolerance. These comorbidities can compound the health risks for affected individuals 2 8 12. There is also a notable prevalence of hypertension in some patients 5.

Psychological Impact

The visible and often disfiguring nature of MSL can lead to psychological distress, social withdrawal, and a reduced quality of life. The psychosocial burden should not be underestimated and is a significant factor in patients’ motivation to seek treatment 3 4 6 15.

Types of Multiple Symmetric Lipomatosis

Understanding the classification of MSL helps clinicians tailor management and anticipate disease progression. Several systems have been proposed, with recent research offering new insights.

Type	Key Features	Prevalence/Pattern	Source(s)
Type I	Cervico-thoracic (neck/shoulders)	Most common, classic type	3 4 6 8
Type II	Upper arms, upper trunk	Less frequent	8
Type III	Lower body, legs	Rare, newly recognized	8
Subtypes Ia-c	Further anatomic localization	Improved classification	8

Table 2: Classification Types

Historical Classifications

Traditionally, MSL has been described based on the anatomical location of the fat deposits:

• Type I (Cervico-thoracic): Fatty masses are predominantly located around the neck, shoulders, and upper back—creating a “horse collar” or “pseudo-athletic” appearance 3 4 6.
• Type II (Upper trunk/arms): Involvement of the upper arms and trunk, with less prominent neck involvement 8.
• Type III (Lower body): Rare variant with predominant involvement of the hips, thighs, and legs 8.

Updated Classification Systems

Recent studies have highlighted the limitations of older classification systems. A large German cohort led to a refined classification that divides MSL into five subtypes (Ia, Ib, Ic, II, and III), accounting for the specific body regions affected. This new system allows for more precise categorization of patients, improving communication and guiding management 8.

Clinical Relevance of Types

The type and distribution of fatty masses can influence both the symptoms experienced and the choice of treatment. For example, extensive neck involvement poses a higher risk for airway compression, while extensive limb involvement may impair mobility 3 4 8.

Gender and Demographic Patterns

MSL has long been regarded as a disease predominantly affecting middle-aged men, especially those from Mediterranean regions. However, recent data suggest the gender ratio may be less skewed than previously believed, and cases are increasingly reported in women 2 6 8.

Causes of Multiple Symmetric Lipomatosis

MSL remains a disease of enigmatic origins, but recent research has provided valuable clues into its underlying mechanisms.

Factor	Role/Mechanism	Notes/Associations	Source(s)
Alcoholism	Strongly associated, >90% of cases	Chronic intake, especially wine	2 3 4 6 12
Mitochondrial Dysfunction	Impaired fat metabolism	Mitochondrial DNA mutations	1 7 9 11 12
Genetic Mutations	MFN2, MERRF, possible autosomal dominant	Familial cases documented	9 12
Brown Fat Abnormalities	Origin of lipomas from brown adipose tissue	UCP-1 expression in lipomas	7 12
Impaired Lipolysis	Defective cAMP-mediated fat breakdown	Hormone resistance	10 11 12
MicroRNA Alterations	Dysregulation in adipogenesis pathways	miR-125a-3p, miR-483-5p	13

Table 3: Proposed Causes

Chronic Alcohol Abuse

The most consistent external factor associated with MSL is chronic, heavy alcohol consumption—often defined as more than 80 grams of alcohol per day for over a decade. Alcohol is believed to promote abnormal adipocyte growth, especially in genetically susceptible individuals. However, not all patients have a history of alcoholism, indicating that other factors must be involved 2 3 4 6 12.

Mitochondrial and Genetic Factors

MSL is increasingly recognized as a mitochondrial disorder, particularly affecting the metabolism of brown adipose tissue (BAT). Mitochondrial DNA mutations, including those seen in MERRF (myoclonic epilepsy with ragged-red fibers), and more recently, pathogenic variants in the MFN2 gene, have been implicated. These defects impair mitochondrial function, leading to abnormal fat accumulation and, in some cases, associated neuropathy 1 7 9 11 12.

Some cases display familial aggregation, suggesting autosomal dominant inheritance. However, most cases remain sporadic 9 12.

Brown Adipose Tissue Dysfunction

MSL lipomas differ from ordinary subcutaneous fat, showing markers typical of brown adipose tissue (such as UCP-1 expression). This suggests that the abnormal growth may originate from BAT precursors, which have increased proliferative capacity and altered metabolic regulation 7 11 12.

Impaired Lipolytic Pathways

Studies have shown that lipomatous tissue in MSL is resistant to catecholamine-stimulated lipolysis, likely due to defects in cyclic AMP-mediated activation of hormone-sensitive lipase. This impaired fat breakdown contributes to the accumulation of fatty masses 10 11 12.

MicroRNA and Stem Cell Abnormalities

Emerging research indicates that specific microRNAs (miR-125a-3p, miR-483-5p) are upregulated in MSL, promoting adipogenesis via suppression of the RhoA/ROCK1/ERK1/2 pathway. Additionally, adipose-derived stem cells from MSL patients display higher proliferative activity, pointing to a stem cell-driven process in the disease’s evolution 11 13.

Treatment of Multiple Symmetric Lipomatosis

While MSL is benign, its complications and impact on quality of life make effective management essential. Treatment primarily focuses on symptom relief and improving function and appearance.

Treatment	Description	Indication/Effectiveness	Source(s)
Surgery	Lipectomy (open removal), excision	Most effective for large masses	2 3 4 6 14 16
Liposuction	Power-assisted/standard liposuction	Less invasive, good for diffuse	14 15 16
Mesotherapy	Phosphatidylcholine injections	Minimally invasive, limited data	17
Alcohol Abstinence	Cessation of alcohol consumption	May slow progression, prevent recurrence	2 3 6 12
Medical Therapy	Address comorbidities (lipid/glucose control)	Supportive, not curative	2 8 12
Airway Management	Tracheostomy in severe compression	Emergency intervention	5

Table 4: Treatment Options

Surgical Removal

Open lipectomy and excision remain the gold standard for managing significant or compressive lipomatous masses. Surgery provides immediate and dramatic symptom relief, particularly in cases of airway or esophageal compromise. However, the diffuse and nonencapsulated nature of the fat can make complete removal difficult, and recurrence is common 2 3 4 6 14 16.

Liposuction Techniques

Liposuction, especially power-assisted (PAL), offers a less invasive alternative that can achieve high patient satisfaction, good cosmetic outcomes, and skin tightening. It is particularly useful for diffuse or superficial deposits. Recurrence rates are variable but generally acceptable, and recovery is often quicker than open surgery 14 15 16.

Mesotherapy

Mesotherapy with phosphatidylcholine injections has shown promise in isolated cases, providing localized fat reduction without surgery. While minimally invasive, larger studies are needed to confirm its long-term efficacy and safety 17.

Alcohol Abstinence

Given the strong association between alcohol and MSL, abstinence is universally recommended. While it may not reverse existing masses, it can slow disease progression and reduce the risk of recurrence after surgery 2 3 6 12.

Managing Comorbidities

Patients with MSL often have associated metabolic disorders such as hyperlipidemia, diabetes, and hypertension. Addressing these conditions is essential for overall health and may indirectly influence disease course 2 8 12.

Airway and Emergency Interventions

In rare, severe cases where masses threaten the airway, urgent interventions such as tracheostomy may be necessary to maintain breathing 5. Such emergencies underscore the importance of early recognition and proactive management.

Long-Term Considerations

Despite treatment, recurrence is common. Lifelong monitoring, repeated interventions, and comprehensive care—including neurological assessment and psychological support—are important for optimizing patient quality of life 2 4 15.

Conclusion

Multiple Symmetric Lipomatosis is a rare but impactful disorder that requires a multidisciplinary approach for optimal management. Recent advances in understanding its pathogenesis and classification are informing better diagnosis and treatment strategies.

Main Points Covered:

• MSL is characterized by symmetric, nonencapsulated fat deposits, most commonly on the neck, shoulders, and upper trunk.
• Symptoms range from cosmetic disfigurement to serious complications like airway compression and neurological deficits.
• Several classification systems exist, with recent updates improving clinical relevance.
• Causes include chronic alcoholism, mitochondrial dysfunction, genetic mutations (such as MFN2), brown fat abnormalities, impaired lipolysis, and microRNA/stem cell dysregulation.
• Treatment is primarily surgical (lipectomy or liposuction), with alcohol abstinence and management of comorbidities as important adjuncts. Minimally invasive therapies are emerging.
• Recurrence is common, necessitating long-term follow-up and supportive care.

Understanding the diverse features and complexities of MSL empowers patients and clinicians to make informed decisions and pursue the best available care.