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Lymphatic malformation 3(LMPHM3)

MedGen UID:
1652857
•Concept ID:
C4747646
•
Disease or Syndrome
Synonyms: LMPHM3; Lymphedema, hereditary, IC
 
Gene (location): GJC2 (1q42.13)
 
Monarch Initiative: MONDO:0013278
OMIM®: 613480

Definition

Hereditary primary lymphedema is caused by anatomic or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes, such as nail dysplasia or papillomatosis. Onset is usually at birth or in early childhood but can occur later, and the severity is variable (summary by Gordon et al., 2013 and Balboa-Beltran et al., 2014). For a discussion of genetic heterogeneity of lymphatic malformation, see 153100. [from OMIM]

Clinical features

From HPO
Cellulitis
MedGen UID:
40174
•Concept ID:
C0007642
•
Disease or Syndrome
A bacterial infection and inflammation of the skin und subcutaneous tissues.
See: Feature record | Search on this feature
Recurrent skin infections
MedGen UID:
377848
•Concept ID:
C1853193
•
Disease or Syndrome
Infections of the skin that happen multiple times.
See: Feature record | Search on this feature
Lymphedema
MedGen UID:
6155
•Concept ID:
C0024236
•
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Juvenile parkinsonism: Differential diagnosis, genetics, and treatment.
Niemann N, Jankovic J
Parkinsonism Relat Disord 2019 Oct;67:74-89. Epub 2019 Jun 30 doi: 10.1016/j.parkreldis.2019.06.025. PMID: 31272925
A review of the management of lymphangiomas.
Ha J, Yu YC, Lannigan F
Curr Pediatr Rev 2014;10(3):238-48. doi: 10.2174/1573396309666131209210751. PMID: 25088344
Normalization of the vasculature for treatment of cancer and other diseases.
Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK
Physiol Rev 2011 Jul;91(3):1071-121. doi: 10.1152/physrev.00038.2010. PMID: 21742796Free PMC Article

Recent clinical studies

Etiology

Neurological manifestation of 22q11.2 deletion syndrome.
Bayat M, Bayat A
Neurol Sci 2022 Mar;43(3):1695-1700. Epub 2022 Jan 18 doi: 10.1007/s10072-021-05825-8. PMID: 35039989
Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
Dar P, Jacobsson B, Clifton R, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Daly S, Hallingström M, MacPherson C, Kao C, Hakonarson H, Norton ME
Am J Obstet Gynecol 2022 Jul;227(1):79.e1-79.e11. Epub 2022 Jan 13 doi: 10.1016/j.ajog.2022.01.002. PMID: 35033576
22q11.2 duplications: Expanding the clinical presentation.
Bartik LE, Hughes SS, Tracy M, Feldt MM, Zhang L, Arganbright J, Kaye A
Am J Med Genet A 2022 Mar;188(3):779-787. Epub 2021 Nov 29 doi: 10.1002/ajmg.a.62577. PMID: 34845825
Neurobiological perspective of 22q11.2 deletion syndrome.
Zinkstok JR, Boot E, Bassett AS, Hiroi N, Butcher NJ, Vingerhoets C, Vorstman JAS, van Amelsvoort TAMJ
Lancet Psychiatry 2019 Nov;6(11):951-960. Epub 2019 Aug 5 doi: 10.1016/S2215-0366(19)30076-8. PMID: 31395526Free PMC Article
Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis.
Grande M, Jansen FA, Blumenfeld YJ, Fisher A, Odibo AO, Haak MC, Borrell A
Ultrasound Obstet Gynecol 2015 Dec;46(6):650-8. doi: 10.1002/uog.14880. PMID: 25900824

Diagnosis

Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
Dar P, Jacobsson B, Clifton R, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Daly S, Hallingström M, MacPherson C, Kao C, Hakonarson H, Norton ME
Am J Obstet Gynecol 2022 Jul;227(1):79.e1-79.e11. Epub 2022 Jan 13 doi: 10.1016/j.ajog.2022.01.002. PMID: 35033576
Prenatal phenotype of 22q11 micro-duplications: A systematic review and report on 12 new cases.
Mary L, Lavillaureix A, Perrot A, Loget P, Launay E, Leborgne AS, Demurger F, Fradin M, Le Bouar G, Quélin C, Dubourg C, Pasquier L, Odent S, Belaud-Rotureau MA, Jaillard S
Eur J Med Genet 2022 Feb;65(2):104422. Epub 2022 Jan 10 doi: 10.1016/j.ejmg.2022.104422. PMID: 35026468
22q11.2 duplications: Expanding the clinical presentation.
Bartik LE, Hughes SS, Tracy M, Feldt MM, Zhang L, Arganbright J, Kaye A
Am J Med Genet A 2022 Mar;188(3):779-787. Epub 2021 Nov 29 doi: 10.1002/ajmg.a.62577. PMID: 34845825
Neurobiological perspective of 22q11.2 deletion syndrome.
Zinkstok JR, Boot E, Bassett AS, Hiroi N, Butcher NJ, Vingerhoets C, Vorstman JAS, van Amelsvoort TAMJ
Lancet Psychiatry 2019 Nov;6(11):951-960. Epub 2019 Aug 5 doi: 10.1016/S2215-0366(19)30076-8. PMID: 31395526Free PMC Article
Practical guidelines for managing adults with 22q11.2 deletion syndrome.
Fung WL, Butcher NJ, Costain G, Andrade DM, Boot E, Chow EW, Chung B, Cytrynbaum C, Faghfoury H, Fishman L, García-Miñaúr S, George S, Lang AE, Repetto G, Shugar A, Silversides C, Swillen A, van Amelsvoort T, McDonald-McGinn DM, Bassett AS
Genet Med 2015 Aug;17(8):599-609. Epub 2015 Jan 8 doi: 10.1038/gim.2014.175. PMID: 25569435Free PMC Article

Therapy

Sirolimus (Rapamycin) for Slow-Flow Malformations in Children: The Observational-Phase Randomized Clinical PERFORMUS Trial.
Maruani A, Tavernier E, Boccara O, Mazereeuw-Hautier J, Leducq S, Bessis D, Guibaud L, Vabres P, Carmignac V, Mallet S, Barbarot S, Chiaverini C, Droitcourt C, Bursztejn AC, Lengellé C, Woillard JB, Herbreteau D, Le Touze A, Joly A, Léauté-Labrèze C, Powell J, Bourgoin H, Gissot V, Giraudeau B, Morel B
JAMA Dermatol 2021 Nov 1;157(11):1289-1298. doi: 10.1001/jamadermatol.2021.3459. PMID: 34524406Free PMC Article
Genetic Basis and Therapies for Vascular Anomalies.
Queisser A, Seront E, Boon LM, Vikkula M
Circ Res 2021 Jun 25;129(1):155-173. Epub 2021 Jun 24 doi: 10.1161/CIRCRESAHA.121.318145. PMID: 34166070
Juvenile parkinsonism: Differential diagnosis, genetics, and treatment.
Niemann N, Jankovic J
Parkinsonism Relat Disord 2019 Oct;67:74-89. Epub 2019 Jun 30 doi: 10.1016/j.parkreldis.2019.06.025. PMID: 31272925
Plastic Bronchitis.
Rubin BK
Clin Chest Med 2016 Sep;37(3):405-8. Epub 2016 Jun 15 doi: 10.1016/j.ccm.2016.04.003. PMID: 27514587
A review of the management of lymphangiomas.
Ha J, Yu YC, Lannigan F
Curr Pediatr Rev 2014;10(3):238-48. doi: 10.2174/1573396309666131209210751. PMID: 25088344

Prognosis

Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
Dar P, Jacobsson B, Clifton R, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Daly S, Hallingström M, MacPherson C, Kao C, Hakonarson H, Norton ME
Am J Obstet Gynecol 2022 Jul;227(1):79.e1-79.e11. Epub 2022 Jan 13 doi: 10.1016/j.ajog.2022.01.002. PMID: 35033576
Neonatal lymphatic flow disorders: impact of lymphatic imaging and interventions on outcomes.
Pinto E, Dori Y, Smith C, DeWitt A, Williams C, Griffis H, Escobar F, Biko DM, Krishnamurthy G, Rome J, Glatz AC, Liu M, Ravishankar C, Zhang H, Taha D
J Perinatol 2021 Mar;41(3):494-501. Epub 2020 Sep 2 doi: 10.1038/s41372-020-00771-3. PMID: 32879418
Vascular anomalies in pediatrics.
Fevurly RD, Fishman SJ
Surg Clin North Am 2012 Jun;92(3):769-800, x. Epub 2012 Apr 26 doi: 10.1016/j.suc.2012.03.016. PMID: 22595720
Primary lymphoedema and lymphatic malformation: are they the two sides of the same coin?
Lee BB, Villavicencio JL
Eur J Vasc Endovasc Surg 2010 May;39(5):646-53. Epub 2010 Feb 21 doi: 10.1016/j.ejvs.2010.01.018. PMID: 20176496
Gallbladder cancer.
Bartlett DL
Semin Surg Oncol 2000 Sep-Oct;19(2):145-55. doi: 10.1002/1098-2388(200009)19:2<145::aid-ssu7>3.0.co;2-6. PMID: 11126379

Clinical prediction guides

Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
Dar P, Jacobsson B, Clifton R, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Daly S, Hallingström M, MacPherson C, Kao C, Hakonarson H, Norton ME
Am J Obstet Gynecol 2022 Jul;227(1):79.e1-79.e11. Epub 2022 Jan 13 doi: 10.1016/j.ajog.2022.01.002. PMID: 35033576
Prenatal phenotype of 22q11 micro-duplications: A systematic review and report on 12 new cases.
Mary L, Lavillaureix A, Perrot A, Loget P, Launay E, Leborgne AS, Demurger F, Fradin M, Le Bouar G, Quélin C, Dubourg C, Pasquier L, Odent S, Belaud-Rotureau MA, Jaillard S
Eur J Med Genet 2022 Feb;65(2):104422. Epub 2022 Jan 10 doi: 10.1016/j.ejmg.2022.104422. PMID: 35026468
Sirolimus (Rapamycin) for Slow-Flow Malformations in Children: The Observational-Phase Randomized Clinical PERFORMUS Trial.
Maruani A, Tavernier E, Boccara O, Mazereeuw-Hautier J, Leducq S, Bessis D, Guibaud L, Vabres P, Carmignac V, Mallet S, Barbarot S, Chiaverini C, Droitcourt C, Bursztejn AC, Lengellé C, Woillard JB, Herbreteau D, Le Touze A, Joly A, Léauté-Labrèze C, Powell J, Bourgoin H, Gissot V, Giraudeau B, Morel B
JAMA Dermatol 2021 Nov 1;157(11):1289-1298. doi: 10.1001/jamadermatol.2021.3459. PMID: 34524406Free PMC Article
A review of the management of lymphangiomas.
Ha J, Yu YC, Lannigan F
Curr Pediatr Rev 2014;10(3):238-48. doi: 10.2174/1573396309666131209210751. PMID: 25088344
Primary lymphoedema and lymphatic malformation: are they the two sides of the same coin?
Lee BB, Villavicencio JL
Eur J Vasc Endovasc Surg 2010 May;39(5):646-53. Epub 2010 Feb 21 doi: 10.1016/j.ejvs.2010.01.018. PMID: 20176496

Recent systematic reviews

Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.
Boot E, Óskarsdóttir S, Loo JCY, Crowley TB, Orchanian-Cheff A, Andrade DM, Arganbright JM, Castelein RM, Cserti-Gazdewich C, de Reuver S, Fiksinski AM, Klingberg G, Lang AE, Mascarenhas MR, Moss EM, Nowakowska BA, Oechslin E, Palmer L, Repetto GM, Reyes NGD, Schneider M, Silversides C, Sullivan KE, Swillen A, van Amelsvoort TAMJ, Van Batavia JP, Vingerhoets C, McDonald-McGinn DM, Bassett AS
Genet Med 2023 Mar;25(3):100344. Epub 2023 Feb 2 doi: 10.1016/j.gim.2022.11.012. PMID: 36729052
Prenatal phenotype of 22q11 micro-duplications: A systematic review and report on 12 new cases.
Mary L, Lavillaureix A, Perrot A, Loget P, Launay E, Leborgne AS, Demurger F, Fradin M, Le Bouar G, Quélin C, Dubourg C, Pasquier L, Odent S, Belaud-Rotureau MA, Jaillard S
Eur J Med Genet 2022 Feb;65(2):104422. Epub 2022 Jan 10 doi: 10.1016/j.ejmg.2022.104422. PMID: 35026468
Sclerotherapy for lymphatic malformations of head and neck: Systematic review and meta-analysis.
De Maria L, De Sanctis P, Balakrishnan K, Tollefson M, Brinjikji W
J Vasc Surg Venous Lymphat Disord 2020 Jan;8(1):154-164. Epub 2019 Nov 14 doi: 10.1016/j.jvsv.2019.09.007. PMID: 31734224
Parkes Weber syndrome-Diagnostic and management paradigms: A systematic review.
Banzic I, Brankovic M, Maksimović Ž, Davidović L, Marković M, Rančić Z
Phlebology 2017 Jul;32(6):371-383. Epub 2016 Aug 9 doi: 10.1177/0268355516664212. PMID: 27511883
Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis.
Grande M, Jansen FA, Blumenfeld YJ, Fisher A, Odibo AO, Haak MC, Borrell A
Ultrasound Obstet Gynecol 2015 Dec;46(6):650-8. doi: 10.1002/uog.14880. PMID: 25900824

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