Lipedema: an inherited condition.
01 Apr 2010-American Journal of Medical Genetics Part A (Am J Med Genet A)-Vol. 152, Iss: 4, pp 970-976
TL;DR: It is proposed that lipedema is a genetic condition with either X‐linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation, and appears to be a condition almost exclusively affecting females, presumably estrogen‐requiring as it usually manifests at puberty.
Abstract: Lipedema is a condition characterized by swelling and enlargement of the lower limbs due to abnormal deposition of subcutaneous fat. Lipedema is an under-recognized condition, often misdiagnosed as lymphedema or dismissed as simple obesity. We present a series of pedigrees and propose that lipedema is a genetic condition with either X-linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation. Lipedema appears to be a condition almost exclusively affecting females, presumably estrogen-requiring as it usually manifests at puberty. Lipedema is an entity distinct from obesity, but may be wrongly diagnosed as primary obesity, due to clinical overlap. The phenotype suggests a condition distinct from obesity and associated with pain, tenderness, and easy bruising in affected areas.
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TL;DR: The lymphatic vascular system is crucial for the regulation of tissue fluid homeostasis, immune function, and fat metabolism, and may lead to lymphedema, a debilitating condition characterized by chronic tissue edema, impaired immunity, and accumulation of subcutaneous fat.
Abstract: The lymphatic vascular system is crucial for the regulation of tissue fluid homeostasis, immune function, and fat metabolism. Lymphatic dysfunction, either due to gene mutations or secondary to damage to the lymph vessels, may lead to lymphedema, a debilitating condition characterized by chronic tissue edema, impaired immunity, and accumulation of subcutaneous fat.
The lymphatic and blood vascular systems function in concert to regulate the tissue fluid homeostasis of the body. The pumping force of the heart generates a hydrostatic pressure, which pushes fluid out of the semipermeable blood capillaries into the interstitial space. Most of the extravasated interstitial fluid and macromolecules are absorbed back by the lymphatic vessels, whereas some reabsorption may also occur in the venules, depending on the tissue (Figure 1).1 Increased endothelial permeability, venous obstruction or insufficiency, and lymphatic vessel dysfunction lead to tissue swelling, or edema (Figure 1).
Figure 1.
Contributions of the blood and lymphatic vascular systems to tissue fluid homeostasis. A through D , Mechanisms leading to tissue edema.1 Normal fluid homeostasis in tissues is schematically illustrated in A : Colloid proteins and associated water are constantly filtrated from the arterial side of the capillary bed into the interstitial space (red arrows). The majority of the filtrate is collected by the lymphatic capillaries (green arrows); some of the fluid may be reabsorbed into the capillaries on the venous side of the capillary bed (blue arrows). B , Under the conditions of increased blood vascular permeability, such as in inflammation, the amount of filtrate is dramatically increased. Although the lymphatic vessels have a remarkable capacity to increase their drainage, sometimes the system is overwhelmed and net edema remains. C , Obstruction of the veins, for example, due to venous thrombosis or venous insufficiency will impair reabsorption (Reabs) and increase blood pressure within the …
150 citations
TL;DR: In this article, lymphatic decongestive therapy, medications and supplements are recommended to reduce the abnormal subcutaneous adipose tissue (SAT) of rare adipose disorders.
Abstract: Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.
123 citations
TL;DR: Early diagnosis and treatment are mandatory for this disorder otherwise gradual enlargement of fatty deposition causes impaired mobility and further comorbidities like arthrosis and lymphatic insufficiency.
Abstract: Lipedema is a disproportionate, symmetrical fatty swelling characterized by pain and bruising existing almost exclusively among women. We undertook a systematic review of the available literature about lipedema, given the lack of knowledge and little evidence about this disorder especially among obesity experts. Diagnosis of lipedema is usually based on clinical features. Symmetrical edema in the lower limbs with fatty deposits located to hips and thighs usually appears at puberty and often affects several members of the same family. Main disorders considered for differential diagnosis are lymphedema, obesity, lipohypertrophy and phlebedema. Treatment protocols comprise conservative (decongestive lymphatic therapy) and surgical (liposuction) approaches. Early diagnosis and treatment are mandatory for this disorder otherwise gradual enlargement of fatty deposition causes impaired mobility and further comorbidities like arthrosis and lymphatic insufficiency.
121 citations
Cites background from "Lipedema: an inherited condition."
...These strong familial background suggests that lipedema is a genetic disorder (22)....
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...have recently found a Pit-1 mutation in members of a family with lipedema (47) and screening of lipedema family members strongly suggests inheritance (22)....
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TL;DR: Surgical therapy with tumescent liposuction is used for about 10 years in women with circumscribed increased subcutaneous fatty tissue, oedema, pain and bruising.
Abstract: Summary
Background Lipoedema is a painful disease in women with circumscribed increased subcutaneous fatty tissue, oedema, pain and bruising. Whereas conservative methods with combined decongestive therapy (manual lymphatic drainage, compression garments) have been well established over the past 50 years, surgical therapy with tumescent liposuction has only been used for about 10 years and long-term results are unknown.
Objectives To determine the efficacy of liposuction concerning appearance (body shape) and associated complaints after a long-term period.
Methods A total of 164 patients who had undergone conservative therapy over a period of years, were treated by liposuction under tumescent local anaesthesia with vibrating microcannulas. In a monocentric study, 112 could be re-evaluated with a standardized questionnaire after a mean of 3 years and 8 months (range 1 year and 1 month to 7 years and 4 months) following the initial surgery and a mean of 2 years and 11 months (8 months to 6 years and 10 months) following the last surgery.
Results All patients showed a distinct reduction of subcutaneous fatty tissue (average 9846 mL per person) with improvement of shape and normalization of body proportions. Additionally, they reported either a marked improvement or a complete disappearance of spontaneous pain, sensitivity to pressure, oedema, bruising, restriction of movement and cosmetic impairment, resulting in a tremendous increase in quality of life; all these complaints were reduced significantly (P < 0·001). Patients with lipoedema stage II and III showed better improvement compared with patients with stage I. Physical decongestive therapy could be either omitted (22·4% of cases) or continued to a much lower degree. No serious complications (wound infection rate 1·4%, bleeding rate 0·3%) were observed following surgery.
Conclusions Tumescent liposuction is a highly effective treatment for lipoedema with good morphological and functional long-term results.
102 citations
TL;DR: The effect of obesity on the skin is reviewed, including how increased body mass index affects skin physiology, skin barrier, collagen structure, and wound healing.
Abstract: Obesity is a worldwide major public health problem with an alarmingly increasing prevalence over the past 2 decades. The consequences of obesity in the skin are underestimated. In this paper, we review the effect of obesity on the skin, including how increased body mass index affects skin physiology, skin barrier, collagen structure, and wound healing. Obesity also affects sebaceous and sweat glands and causes circulatory and lymphatic changes. Common skin manifestations related to obesity include acanthosis nigricans, acrochordons, keratosis pilaris, striae distensae, cellulite, and plantar hyperkeratosis. Obesity has metabolic effects, such as causing hyperandrogenism and gout, which in turn are associated with cutaneous manifestations. Furthermore, obesity is associated with an increased incidence of bacterial and Candida skin infections, as well as onychomycosis, inflammatory skin diseases, and chronic dermatoses like hidradenitis suppurativa, psoriasis, and rosacea. The association between atopic dermatitis and obesity and the increased risk of skin cancer among obese patients is debatable. Obesity is also related to rare skin conditions and to premature hair graying. As physicians, understanding these clinical signs and the underlying systemic disorders will facilitate earlier diagnoses for better treatment and avoidance of sequelae.
78 citations
References
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TL;DR: Type or categories of scalp hairiness which can be used as standards for classitication and grading of the extent of common baldness are established and the relationship of scdp types to factors which influence the development of baldness is studied.
Abstract: This account summarizes certain aspects of a study which is to be published in detail eisewhere and has the following aims: (1) To establish types or categories of scalp hairiness which can be used as standards for classitication and grading of the extent of common ba1dness.t (2) To survey the incidence of these scalp types in members of each sex throughout life, beginning with the first appearance of hair in the fetus. (3) To gain information regarding the relationship of scdp types to factors which influence the development of baldness, in particular to genetic, age, and endocrine factors. (4) To ascertain if bald men, as compared with men who did not become bald, have higher titers of urinary ketosteroids or a greater development of a secondary sex character, axillary hair, which can be measured quantitatively and used as an index of certain aspects of the endocrine status. This part af the study stems from the fact that common baldness is induced by androgenic stimulation (Hamilton, 1942). ( 5 ) To test if the tendency to acquire baldness of the scalp is associated with a disposition to baldness on another part of the body where alopecia is common, i e . , on the lateral surfaces of the legs.
770 citations
TL;DR: COS-7 cells expressing the mutant LH receptor exhibited markedly increased cyclic AMP production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LH receptor.
Abstract: Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. Affected males generally exhibit signs of puberty by age 4. Testosterone production and Leydig cell hyperplasia occur in the context of prepubertal levels of luteinizing hormone (LH). The LH receptor is a member of the family of G-protein-coupled receptors, and we hypothesized that FMPP might be due to a mutant receptor that is activated in the presence of little or no agonist. A single A-->G base change that results in substitution of glycine for aspartate at position 578 in the sixth transmembrane helix of the LH receptor was found in affected individuals from eight different families. Linkage of the mutation to FMPP was supported by restriction-digest analysis. COS-7 cells expressing the mutant LH receptor exhibited markedly increased cyclic AMP production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LH receptor.
707 citations
"Lipedema: an inherited condition." refers background in this paper
...gene that codes for the receptor for luteinizing hormone [Schedewie et al., 1981; Shenker et al., 1993]....
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...The latter condition is inherited in an autosomal dominant manner, and is due to mutations in the gene that codes for the receptor for luteinizing hormone [Schedewie et al., 1981; Shenker et al., 1993]....
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TL;DR: In this paper, a systematic resequencing of 737 X chromosome genes was carried out to identify different protocadherin 19 (PCDH19) gene mutations in seven families with EFMR.
Abstract: Epilepsy and mental retardation limited to females (EFMR) is a disorder with an X-linked mode of inheritance and an unusual expression pattern. Disorders arising from mutations on the X chromosome are typically characterized by affected males and unaffected carrier females. In contrast, EFMR spares transmitting males and affects only carrier females. Aided by systematic resequencing of 737 X chromosome genes, we identified different protocadherin 19 (PCDH19) gene mutations in seven families with EFMR. Five mutations resulted in the introduction of a premature termination codon. Study of two of these demonstrated nonsense-mediated decay of PCDH19 mRNA. The two missense mutations were predicted to affect adhesiveness of PCDH19 through impaired calcium binding. PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation.
359 citations
01 Jan 2009
TL;DR: Seven protocadherin 19 (PCDH19) gene mutations in seven families with EFMR resulted in the introduction of a premature termination codon and two missense mutations were predicted to affect adhesiveness of PCDH19 through impaired calcium binding.
337 citations
"Lipedema: an inherited condition." refers background in this paper
...The former shows X-linked dominant inheritance, and the causative gene is protocadherin 19 [Dibbens et al., 2008]....
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TL;DR: There is little in the literature on abnormal localized depositions of body fat to clarify the syndrome of lipedema of the legs, but two of us (E. V. and E. A. H.) described it in 1940.
Abstract: Excerpt There is little in the literature on abnormal localized depositions of body fat to clarify the syndrome of lipedema of the legs which two of us (E. V. A. and E. A. H.) described in 1940.1Co...
188 citations
"Lipedema: an inherited condition." refers background in this paper
...Affected individuals develop bilateral and symmetrical ‘‘fatty’’ non-pitting swelling usually confined to the legs and hips [Wold et al., 1951]....
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