Familial Multiple Lipomatosis Research Articles

Lipomatoses

Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple, encapsulated or not, subcutaneous or sometimes visceral. In some cases, they form large areas of non-encapsulated fat hypertrophy, with a variable degree of fibrosis. They can develop despite the absence of obesity. They may be familial or acquired. At difference with lipodystrophy syndromes, they are not associated with lipoatrophy areas, except in some rare cases such as type 2 familial partial lipodystrophy syndromes (FPLD2). Their metabolic impact is variable in part depending on associated obesity. They may have functional or aesthetic consequences. Lipomatosis may be isolated, be part of a syndrome, or may be visceral. Isolated lipomatoses include multiple symmetrical lipomatosis (Madelung disease or Launois-Bensaude syndrome), familial multiple lipomatosis, the painful Dercum's disease also called Adiposis Dolorosa or Ander syndrome, mesosomatic lipomatosis also called Roch-Leri lipomatosis, familial angiolipomatosis, lipedema and hibernomas. Syndromic lipomatoses include PIK3CA-related disorders, Cowden/PTEN hamartomas-tumor syndrome, some lipodystrophy syndromes, and mitochondrial diseases, especially MERRF, multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson disease, Pai or Haberland syndromes. Finally, visceral lipomatoses have been reported in numerous organs and sites: pancreatic, adrenal, abdominal, epidural, mediastinal, epicardial… The aim of this review is to present the main types of lipomatosis and their physiopathological component, when it is known.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

A rare case report of familial multiple lipomatosis and its diagnostic approach with review of literatures

Lipoma is a well-known and most common soft tissue tumor. But multiple lipomatosis are rare. Also, syndromic associations were documented. Familial multiple lipomatosis (FML) is an autosomal dominant disorder. It presents as multiple lipomas in the body at specific sites. In presenting case 26-year-old patient complained of multiple swellings in his forearms, both thigh, and anterior abdominal wall for 5 years. A diagnosis of multiple lipomatosis is made by Fine needle aspiration cytology and confirmed by histopathological examination.

Familial Multiple Lipomatosis: A Case Report

A 32-year-old man presents to the clinic with multiple subcutaneous masses. Further history and a review of the literature are discussed. This is a case study of a patient with familial multiple lipomatosis and our management. Liposuction was performed after informed consent was obtained to manage familial multiple lipomatosis in an aesthetically pleasing manner without recurrence. Liposuction is an excellent technique for an aesthetically pleasing outcome to manage familial multiple lipomatosis. Additional therapy modalities including laser, chemicals, high-pressure tumescent injection, and Vibration Amplification of Sound Energy at Resonance (VASER) are reviewed. To avoid multiple incisions and scars, liposuction for familial multiple lipomatosis is an aesthetically pleasing, definitive treatment modality with no recurrence of lipomas.

Lipomas: genetic basis of common skin lesions and their occurrence in rare diseases.

Lipomas are usually sporadic, asymptomatic lesions, and their clinical and histologic presentation does not pose diagnostic difficulties. In ambiguous cases, however, knowledge of genetics is necessary. HMGA2 expression in adipose cells enables the differentiation of normal adipose tissue from lipoma and liposarcoma. Moreover, lipomas can be associated with genetic diseases, such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson's disease, or mitochondrial diseases. Lipomas can run in families (familial multiple lipomatosis) or be a part of genetic syndromes such as PTEN hamartoma tumor syndrome, Proteus syndrome, and Pai syndrome. This study aims to present the genetic basis of lipomas and diseases in which these lesions occur in the clinical picture.

A 57-year-old alcoholic woman with soft neck mass

A 57-year-old woman was diagnosed with an anterior cervical mass (figure 1). No peripheral neuropathy or cervical lymph nodes were detected from the physical examination. The mass has slowly and painlessly grown for 30 years with no dyspnea or dysphagia. She had a history of chronic alcohol consumption and heavy tobacco use for 25 years. No standard medications were taken.
 Multiple symmetric lipomatosis is a disease characterized by the accumulation of multiple, benign, symmetric, and nonencapsulated fatty tissue masses. This is more common in males (15:1) and in the Mediterranean population. Malignancy is rarely observed in this case. Masses can be found on the head and neck, including the upper trunk, shoulders, upper back, mediastinum, perineum, scrotum, and tongue. Besides the aesthetic effects, masses can cause airways or digestive compressive symptoms, as well as limitations in head or neck movements, urinating, or sexual intercourse. The involvement of peripheral nerves can cause neurological symptoms.
 
 Alcohol abuse has been long associated with this disease. A genetic cause has been suggested, but a hereditary pattern has not been identified in most cases. A link was suggested with liver disease, but there is no mention of liver abscess in the literature.
 
 The diagnostic is based on image finds. Solitary lipoma is a benign soft tissue tumor, rarely found in the neck region. It mostly occurs in females and obese patients, and it is enclosed by a fibrous capsule that helps to differentiate it from other fat aggregations. Liposarcoma represents 1% of neck and head sarcomas. Patients are mostly men and the medium age is 70 years. Familial multiple lipomatosis is a rare autosomal dominant disease that is manifested in the thirties and is more prevalent in females (2:1). In this case, the discrete multiple subcutaneous nodules are movable, painless, and soft and have no associated conditions.
 
 Lipectomy is the concerned treatment, but recurrence is common. Liposuction is an alternative to extensive lipectomy. No medicinal therapy is effective; however, alcohol abstinence can reduce the recurrence frequency.
 
 Clinics must be aware of this uncommon disease in order to diagnose it and treat it appropriately.
 
 Statement of Ethics
 Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
 
 Conflict of Interest Statement
 The authors have no conflicts of interest to declare.
 
 Funding Sources
 The authors had no funding sources in the preparation of data or the manuscript.

Multiple symmetric and multiple familial lipomatosis

Lipomas are the most common soft tissue tumors and are malignant in only 1% of cases. Lipomatosis is defined as the presence of multiple benign lipomas on the body, without lipoatrophy. Their impact on quality of life is significant. Different entities have been described such as symmetrical multiple lipomatosis (MSL), also called Madelung's disease and familial multiple lipomatosis (FML). MSL occurs preferentially in men (but also women) who are alcohol abuser. There are different subtypes of the disease, the most classic of which affects the upper body and the nuchal region with a buffalo hump appearance. A metabolic component with obesity is frequent. In contrast to Dercum's disease, there is no pain. SAOS, complications of the metabolic syndrome and of alcohol abuse including cancers, may be associated and should be screened. FML has been little described in the literature since Brodie's first report in 1846. FML occurs preferentially in the third decade but equally in women and men. Its autosomal dominant component is classically accepted with variable penetrance within the same family. Association with naevi, angiomas, polyneuropathies and with gastrointestinal comorbidities has been reported. Interestingly, and in contrast with most lipodystrophy disorders, the patients show an insulin sensitivity profile. A better understanding of the underlying pathophysiological mechanisms would open up avenues on therapeutic research, since treatments are only symptomatic to date.

26286 Familial multiple lipomatosis: A reported case and brief review of similar diagnoses characterized by multiple lipomas

Familial multiple lipomatosis (FML) is a rare genetic disorder characterized by many encapsulated lipomas with a predilection for the trunk and extremities. Although it is benign, it carries with it a distinctive clinical presentation. FML should be distinguished from multiple symmetric lipomatosis (MSL), characterized by symmetric fatty infiltration of underlying tissue typically in the neck and shoulder areas and associated with alcoholism. There is a very low risk of malignant transformation to liposarcoma from lipomas of FML. The only treatment for FML is excision, and the concerns are usually cosmetic. We present a case of FML in a 48-year-old male with multiple subcutaneous soft nodules on the arms and lower trunk since the age of 14. We also conduct a brief review of the literature of FML as well as MSL and sporadic multiple lipomatosis, a separate disorder with clinical similarity to FML but with no documented family history of multiple lipomas.

A REVIEW ON LIPOMA AND ITS GENETIC INTERVENTIONS

Lipomas are benign soft tissue fatty tumours that most commonly appear in the third decade of life when fatty tissue accumulates. Histologically, lipoma is composed of mature fat cells with a thin fibrous capsule. Simple lipomas account for 80% of adipose tissue tumours. The aetiology may be genetic like Familial Multiple Lipomatosis. Some tumours, like the well differentiated Liposarcomas never metastasize unless they undergo de-differentiation. They can be introduced as Atypical Lipomatous Tissue, ALT. Southern blot analysis is performed by obtaining DNA from ALT, cases in which most of them are characterized by the presence of supernumerary ring and long marker chromosomes. The complex chromosome region contains genes MDM2, CDK4, HMGI- C, SAS, GLI, CHOP, OS4 and OSP. Most of ALTs, after analysis revealed amplification of CDK4 and MDM2 proto- oncogenes that play major role in permitting over ride of block operated on cell proliferation. Immuno-histochemical results have shown MDM2 over expression in about 50% of ALTs along with weak CDK4 immuno-positivity. Also the lipomas with Gene fusion transcripts have the expression of certain genes, HMGA2/LPP, HMGA2/RDCI and HMGA2/NFIB. Of these 98% of cases were analyzed for the possible expression of HMGA2/LPP and LPP- HMGA2 fusion genes using reverse transcription polymerase chain reaction. Over all these cases, shows non-enhanced adipocyte apoptosis and enhanced adipogenesis in lipoma tissue. Thus studies provide insights into molecular pathogenesis of lipomatous tumour and representation of distinctive subset of mesenchymal neoplasms with mature adipocyte differentiation.

Clinical and Molecular Investigation of Familial Multiple Lipomatosis: Variants in the HMGA2 Gene.

BackgroundFamilial multiple lipomatosis (FML) is an autosomal dominant disorder characterized by the slow growth of encapsulated nodules spread across the trunk and limbs. Currently, there is no specific etiology; therefore, its molecular and biological bases need to be better understood. High-throughput sequencing technologies appear to be a cost-effective tool and have a pivotal role in elucidating different genodermatoses.ObjectiveThis study aimed to perform a clinical and molecular characterization of constitutional DNA of seven individuals belonging to five unrelated families diagnosed with FML.Patients and methodsClinical aspects were obtained from medical records and physical examination. HMGA2 gene was investigated using Sanger sequencing method. Mutational analysis of other genes associated with syndromic lipomatosis AKT1, APC, PIK3CA, MEN-1, and PTEN was performed through next-generation sequencing.ResultsIn this series, FML was predominant among women who were overweight and reaching the age of thirty and was associated with gastrointestinal comorbidity. Histopathological diagnosis of biopsies revealed typical features of both lipoma and angiolipoma. We identified two identical novel variants with unknown significance in exon 5 of the HMGA2 gene in two participants of different families. There were no additional changes in exons 1 to 4 of the HMGA2 gene. Multi-gene panel was normal in all cases.ConclusionVariants found in exon 5 of the HMGA2 gene have not been described and have an uncertain significance in the genesis of FML. Further studies, including a more significant number of affected individuals and functional analysis of the novel variants of HGMA2 gene, should be undertaken to better understand its biological role in FML.

Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis

Little is known on the causes and pathogenesis of the adipose tissue disorder (familial) Multiple Symmetric Lipomatosis (MSL). In a four-generation MSL-family, we performed whole exome sequencing (WES) in 3 affected individuals and 1 obligate carrier and identified Calcyphosine-like (CAPSL) as the most promising candidate gene for this family. Screening of 21 independent patients excluded CAPSL coding sequence variants as a common monogenic cause, but using immunohistochemistry we found that CAPSL was down-regulated in adipose tissue not only from the index patient but also in 10 independent sporadic MSL-patients. This suggests that CAPSL is regulated in sporadic MSL irrespective of the underlying genetic/multifactorial cause. Furthermore, we cultivated pre-adipocytes from MSL-patients and generated 3T3-L1-based Capsl knockout and overexpressing cell models showing altered autophagy, adipogenesis, lipogenesis and Sirtuin-1 (SIRT1) expression. CAPSL seems to be involved in adipocyte biology and perturbation of autophagy is a potential mechanism in the pathogenesis of MSL. Downregulation of CAPSL and upregulation of UCP1 were common features in MSL fat while the known MSL genes MFN2 and LIPE did not show consistent alterations. CAPSL immunostainings could serve as first diagnostic tools in MSL clinical care with a potential to improve time to diagnosis and healthcare options.

Lipoma

This soft-tissue tumor was removed from the thigh. The photograph shows a cross section of a well-delineated, irregularly lobulated, pale yellow lipoma. What is most accurate regarding lipomas?a.Lipomas are usually identified in children and are rare in adultsb.Lipomas frequently have chromosomal aberrationsc.Multiple lipomas are more common than solitary lipomasd.Most lipomas occur in the setting of a genetic syndrome Answer: b. Lipomas frequently have chromosomal aberrations Lipomas are benign, often asymptomatic tumors that are most often identified in adults. Lipomas are usually subcutaneous or superficial, and deep lipomas are less common. Although benign, most lipomas are associated with chromosomal aberrations. Aberrations involving 12q13-15 are common in conventional lipomas and may involve the HMGA2 gene, but other chromosomal aberrations can also occur.1Bartuma H. Hallor K.H. Panagopoulos I. et al.Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype.Genes Chromosomes Cancer. 2007; 46: 594-606Crossref PubMed Scopus (66) Google Scholar, 2Gamez J. Playan A. Andreu A.L. et al.Familial multiple symmetric lipomatosis associated with the A8344G mutation of mitochondrial DNA.Neurology. 1998; 51: 258-260Google Scholar Most lipomas are solitary tumors, but multiple lipomas can occur, including in syndromes such as familial multiple lipomatosis.

Subcutaneous Nodules in a Kidney Transplant Recipient: Familial Multiple Lipomatosis

Subcutaneous Nodules in a Kidney Transplant Recipient: Familial Multiple Lipomatosis

Bariatric Endocrinology, Adiposopathy, and Disorders of Regional Fat Distribution

Bariatric Endocrinology, Adiposopathy, and Disorders of Regional Fat Distribution

A rare case of familial multiple subcutaneous lipomatosis with novel PALB2 mutation and increased predilection to cancers

We describe the association of familial multiple subcutaneous lipomatosis with a PALB2 gene mutation (c.2716delT) and its increased predilection to cancers.

Familial multiple lipomatosis and #8212;a rare syndrome diagnosed on FNAC

Familial multiple lipomatosis (FML) is a very rare benign condition with the prevalence of 0.002% in general population (1:50,000). It is inherited as an autosomal dominant disease. It is more prevalent in men. It is characterized by multiple, soft-tissue swellings on hand, forearm, thigh, and abdomen. We are presenting this case of a 24-year-old man with the clinical and cytological pictures of FML with a family history to put more emphasis on its differential diagnosis of multiple symmetric lipomatosis and the use of fine needle aspiration cytology as a definitive diagnostic tool for these soft-tissue lesions.

Syndromic lipomatosis of the head and neck: a review of the literature.

Patients with syndromic causes of lipomatosis of the head and neck, although rare, often present late in the course of the disease in a myriad of ways, including concomitant airway obstruction, severe functional limitations, and/or significant cosmetic defects. The goal of this report was to review the literature and present a concise overview of the major syndromes causing lipomatosis of the head and neck. A literature search was performed to gather information on syndromic lipomatosis of the head and neck region. PubMed was searched for the following conditions: Familial multiple lipomatosis (FML), multiple symmetrical lipomatosis (MSL), congenital infiltrating lipomatosis of the face (CIL-F), and Nasopalpebral lipoma-coloboma syndrome (NLCS). Data gathered included results of surgical cases of the head and neck region. A total of 48 reports comprising 172 cases of syndromic lipomatosis of the head and neck region were deemed eligible for review. Eighty-five percent of patients were male with an average age of 35 years. Seventy-four percent of cases appeared in the neck region, whereas 23 % presented in the face and scalp. 89 % of cases were treated with surgical excision, with 11 % of cases treated with liposuction. The most common complications were hematoma and seroma in MSL, recurrence in FML, neuropraxia in CIL-F, and mild telecanthus in NLCS. Syndromic causes of lipomatosis are generally benign in nature but difficult to control long term. Because these conditions include frequent recurrence and subsequent difficulty in clearing the disease, the authors advocate early and aggressive surgical excision of syndromic lipomatosis. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Retinoblastoma plus lipomatosis: an autosomal dominant syndrome.

Retinoblastoma plus lipomatosis: an autosomal dominant syndrome.

Letter to the Editor Madelung’s disease in a patient with chronic alcohol abuse

A 47-year-old man with a history of chronic alcohol abuse was admitted to our hospital because of symmetrical face soft tissue enlargement for differential diagnosis. The lesions had appeared 4 years earlier and had been asymptomatic. Physical examination revealed painless, elastic tumors of the subcutaneous tissue in the mandibular angle region, with no clear relation to lymph nodes or salivary glands (Figure 1A). The laboratory tests showed elevated aspartate aminotransferase (ALT), 127 U/l; elevated alanine aminotransferase (ALT), 91 U/l, elevated γ-glutamyl transpeptidase (GGT), 643 U/l, and elevated lactate dehydrogenase (LDH) activity, 342 U/l. Test for antinuclear antibodies (ANA) was negative. HIV and HCV infections were excluded. Lipid profile results were within the normal range. An abdominal ultrasound revealed a fatty liver, but no other abnormality was noted. Ultrasonography of the parotid, submandibular and cervical region confirmed the correct size and structure of the salivary and thyroid glands and slight enlargement of the lymph nodes in both submandibular regions. In the place of visible symmetric thickening there was a tissue described as lipofibroma, 49 mm × 24 mm on the right side and 44 mm × 23 mm in size on the left side. Fine-needle biopsy revealed lipomatous tissue. A diagnosis of Madelung's disease was made. Figure 1 A – Frontal view of the patient at time of first hospitalization with visible symmetrical fatty masses. B, C – Frontal and lateral view of the patient at follow-up visit after 1 year; increase in the primary fatty deposit At the follow-up visit after 1 year, the patient had a computed tomography (CT) scan performed, which showed a slight increase in the primary fatty deposit and the appearance of another in the neck area (Figure 2A–C). Six months later the patient was disqualified from surgical treatment. The decision was motivated by the non-life-threatening condition and asymptomatic nature of the masses. Figure 2A–C Head and neck CT showing the symmetrical enhancement of the lipomatous tissue Madelung's disease (also known as benign symmetric lipomatosis or Launois-Bensaude syndrome) is a rare metabolic disorder of unknown etiology [1]. This disease usually affects men at the age of 30 to 60 years from the Mediterranean area. In reported cases, almost 90% of patients had a history of long-term alcohol abuse [2]. The disease is characterized by the presence of prominent, symmetrical deposits of non-encapsulated adipose tissue in the region of head, neck, nape and upper parts of the trunk [2, 3]. In contrast to other cases described in the literature, in our patient, the primary subcutaneous fat masses appeared in the parotid region, while the most common initial location is the neck. Although benign in nature, sometimes the fatty masses can reach very large sizes causing dyspnea, dysphagia, fatigue, and reduced neck movement ability [4]. The differential diagnosis includes familial multiple lipomatosis, simple obesity, Cushing's syndrome, angiolipoma, neurofibroma and liposarcoma [2, 4, 5]. The most effective treatment is surgery, especially in patients with esthetic deformity or compression of the aerodigestive tract [1, 3].

Do you know this syndrome?

Lipomas are among the most common tumors seen in the soft body parts and usually are solitary lesions. The authors report a case of a male patient that presented for evaluation of multiple subcutaneous nodules that caused important functional and cosmetic impairment. The diagnosis of familial multiple lipomatosis was made. Physicians should be able to recognize and characterize this rare disease.