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Multiple symmetric lipomatosis(MSL)

MedGen UID:
7349
Concept ID:
C0023804
Disease or Syndrome
Synonyms: Benign symmetrical lipomatosis; Launois-Bensaude syndrome; Lipodystrophy, cephalothoracic; Lipomatosis familial benign cervical; Madelung disease; Madelung's disease
SNOMED CT: Multiple symmetrical lipomatosis (238902007); LMS - Multiple symmetrical lipomatosis (238902007); Launois Bensaude lipomatosis (238902007); Madelung disease (238902007); Madelung neck (238902007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Mitochondrial inheritance
MedGen UID:
165802
Concept ID:
C0887941
Genetic Function
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy).
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): MFN2 (1p36.22)
 
Monarch Initiative: MONDO:0007908
OMIM®: 151800
Orphanet: ORPHA2398

Definition

Multiple symmetric lipomatosis (MSL) is an autosomal recessive metabolic disorder characterized by the growth of unencapsulated masses of adipose tissue with predilection for the cervical and thoracic regions. The lipoma growth is striking and disfiguring, and growth around the neck may cause difficulty swallowing or breathing. The age at onset ranges from childhood to young adulthood. Most, but not all, patients develop axonal peripheral neuropathy, which can appear at any age and varies in severity. Laboratory studies in MSL show low leptin (164160), low adiponectin (605441), variably increased lactate, and increased FGF21 (609436). Some patients may have insulin resistance. The disorder is exclusively associated with a particular MFN2 mutation (R707W; 608507.0013), usually in the homozygous state, but sometimes in the compound heterozygous state (Rocha et al., 2017; Capel et al., 2018). [from OMIM]

Clinical features

From HPO
Multiple lipomas
MedGen UID:
677074
Concept ID:
C0745730
Finding
The presence of multiple lipomas (a type of benign tissue made of fatty tissue).
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Progressive muscle weakness
MedGen UID:
68704
Concept ID:
C0240421
Finding
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.

Professional guidelines

PubMed

Hansson E, Svensson H, Brorson H
Orphanet J Rare Dis 2012 Apr 30;7:23. doi: 10.1186/1750-1172-7-23. PMID: 22546240Free PMC Article

Recent clinical studies

Etiology

Precone V, Barati S, Paolacci S, Salgarello M, Visconti G, Gentileschi S, Guerri G, Gagliardi L, Aquilanti B, Matera G, Velluti V, Miggiano GAD, Herbst KL, Bertelli M
Acta Biomed 2019 Sep 30;90(10-S):90-92. doi: 10.23750/abm.v90i10-S.8767. PMID: 31577262Free PMC Article
Bassetto F, Scarpa C, De Stefano F, Busetto L
Ann Plast Surg 2014 Nov;73(5):559-62. doi: 10.1097/SAP.0b013e31827f5295. PMID: 23657050
Gomes da Silva R, Detoffol Bragança R, Ribeiro Costa C, Torres de Melo L, Weiss Telles R, Costa Silva L
J Cutan Med Surg 2011 Jul-Aug;15(4):230-5. doi: 10.2310/7750.2011.10026. PMID: 21781630
Lee HW, Kim TH, Cho JW, Ryu BY, Kim HK, Choi CS
Dermatol Surg 2003 Mar;29(3):235-40. doi: 10.1046/j.1524-4725.2003.29056.x. PMID: 12614415
Enzi G, Busetto L, Ceschin E, Coin A, Digito M, Pigozzo S
Int J Obes Relat Metab Disord 2002 Feb;26(2):253-61. doi: 10.1038/sj.ijo.0801867. PMID: 11850759

Diagnosis

Lemaitre M, Chevalier B, Jannin A, Bourry J, Espiard S, Vantyghem MC
Presse Med 2021 Nov;50(3):104077. Epub 2021 Oct 21 doi: 10.1016/j.lpm.2021.104077. PMID: 34687914
Precone V, Barati S, Paolacci S, Salgarello M, Visconti G, Gentileschi S, Guerri G, Gagliardi L, Aquilanti B, Matera G, Velluti V, Miggiano GAD, Herbst KL, Bertelli M
Acta Biomed 2019 Sep 30;90(10-S):90-92. doi: 10.23750/abm.v90i10-S.8767. PMID: 31577262Free PMC Article
Prahlow SP, Kosciuk P, Prahlow JA
J Forensic Sci 2018 Jan;63(1):312-315. Epub 2017 Jun 23 doi: 10.1111/1556-4029.13536. PMID: 28643398
Hudzik B, Szkodziński J, Gąsior M, Zubelewicz-Szkodzińska B
Pol Arch Intern Med 2017 Jun 30;127(6):450-451. Epub 2017 Jun 29 doi: 10.20452/pamw.4050. PMID: 28680030
Gomes da Silva R, Detoffol Bragança R, Ribeiro Costa C, Torres de Melo L, Weiss Telles R, Costa Silva L
J Cutan Med Surg 2011 Jul-Aug;15(4):230-5. doi: 10.2310/7750.2011.10026. PMID: 21781630

Therapy

Caretto A, Errichiello E, Patricelli MG, Zuffardi O, Cristel G, Ravelli S, Sirtori M, Scavini M, Bosi E, Martinenghi S
Medicine (Baltimore) 2021 Dec 23;100(51):e28360. doi: 10.1097/MD.0000000000028360. PMID: 34941153Free PMC Article
Busetto L, Sträter D, Enzi G, Coin A, Sergi G, Inelmen EM, Pigozzo S
Int J Obes Relat Metab Disord 2003 Nov;27(11):1419-22. doi: 10.1038/sj.ijo.0802427. PMID: 14574355
Cossarizza A, Mussini C, Viganò A
Bioessays 2001 Nov;23(11):1070-80. doi: 10.1002/bies.1152. PMID: 11746223
Martínez-Escribano JA, Gonzalez R, Quecedo E, Febrer I
Int J Dermatol 1999 Jul;38(7):551-4. doi: 10.1046/j.1365-4362.1999.00743.x. PMID: 10440290
Stavropoulos PG, Zouboulis CC, Trautmann C, Orfanos CE
Dermatology 1997;194(1):26-31. doi: 10.1159/000246052. PMID: 9031787

Prognosis

Sawyer SL, Cheuk-Him Ng A, Innes AM, Wagner JD, Dyment DA, Tetreault M; Care4Rare Canada Consortium, Majewski J, Boycott KM, Screaton RA, Nicholson G
Hum Mol Genet 2015 Sep 15;24(18):5109-14. Epub 2015 Jun 17 doi: 10.1093/hmg/ddv229. PMID: 26085578
Hansson E, Svensson H, Brorson H
Orphanet J Rare Dis 2012 Apr 30;7:23. doi: 10.1186/1750-1172-7-23. PMID: 22546240Free PMC Article
Yoshioka N, Suzuki S
Ann Plast Surg 1989 Nov;23(5):456-8. doi: 10.1097/00000637-198911000-00015. PMID: 2690720

Clinical prediction guides

Prahlow SP, Kosciuk P, Prahlow JA
J Forensic Sci 2018 Jan;63(1):312-315. Epub 2017 Jun 23 doi: 10.1111/1556-4029.13536. PMID: 28643398
Sawyer SL, Cheuk-Him Ng A, Innes AM, Wagner JD, Dyment DA, Tetreault M; Care4Rare Canada Consortium, Majewski J, Boycott KM, Screaton RA, Nicholson G
Hum Mol Genet 2015 Sep 15;24(18):5109-14. Epub 2015 Jun 17 doi: 10.1093/hmg/ddv229. PMID: 26085578
Tremp M, Wettstein R, Tchang LA, Schaefer DJ, Rieger UM, Kalbermatten DF
Surg Obes Relat Dis 2015 Jan-Feb;11(1):155-60. Epub 2014 May 16 doi: 10.1016/j.soard.2014.05.004. PMID: 25393046
Lee HW, Kim TH, Cho JW, Ryu BY, Kim HK, Choi CS
Dermatol Surg 2003 Mar;29(3):235-40. doi: 10.1046/j.1524-4725.2003.29056.x. PMID: 12614415
Enzi G, Busetto L, Ceschin E, Coin A, Digito M, Pigozzo S
Int J Obes Relat Metab Disord 2002 Feb;26(2):253-61. doi: 10.1038/sj.ijo.0801867. PMID: 11850759

Recent systematic reviews

Liu Q, Lyu H, Xu B, Lee JH
Aesthetic Plast Surg 2021 Jun;45(3):977-986. Epub 2021 Jan 25 doi: 10.1007/s00266-020-02083-5. PMID: 33492475

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