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Lymphatic malformation 12(LMPHM12)

MedGen UID:
1823976
Concept ID:
C5774203
Disease or Syndrome
Synonyms: CENTRAL CONDUCTING LYMPHATIC ANOMALY; LMPHM12
 
Gene (location): MDFIC (7q31.1-31.2)
 
Monarch Initiative: MONDO:0031043
OMIM®: 620014

Definition

Lymphatic malformation-12 (LMPHM12) is characterized by abnormalities in the development and function of major truncal lymphatic vessels, causing nonimmune hydrops fetalis that results in stillbirth in some cases. Other affected individuals experience postnatal subcutaneous lymphedema and chylothorax, with pleural and pericardial effusions and ascites (Byrne et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of lymphatic malformation, see LMPHM1 (153100). [from OMIM]

Clinical features

From HPO
Hydrocele testis
MedGen UID:
318568
Concept ID:
C1720771
Congenital Abnormality
Accumulation of clear fluid in the between the layers of membrane (tunica vaginalis) surrounding the testis.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Pleural thickening
MedGen UID:
538648
Concept ID:
C0264545
Disease or Syndrome
An increase in the thickness of the pleura, generally related to scarring of the pleural tissue.
Recurrent upper and lower respiratory tract infections
MedGen UID:
375014
Concept ID:
C1842777
Finding
Increased susceptibility to upper and lower respiratory tract infections, as manifested by recurrent episodes of upper and lower respiratory tract infections.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Lymphedema
MedGen UID:
6155
Concept ID:
C0024236
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Non-immune hydrops fetalis
MedGen UID:
105327
Concept ID:
C0455988
Disease or Syndrome
Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100).
Fetal ascites
MedGen UID:
226930
Concept ID:
C1285291
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity during the fetal period.
Fetal pleural effusion
MedGen UID:
759277
Concept ID:
C3532164
Pathologic Function
Fetal pleural effusion is the accumulation of excess fluid in the layers of tissue (pleura) lining the lungs and wall of the chest. It may be primary, also termed hydrothorax, occurring as an isolated finding or it may be secondary, most commonly resulting from non-immune hydrops.
Fetal pericardial effusion
MedGen UID:
759278
Concept ID:
C3532165
Pathologic Function
An abnormal accumulation of fluid in which the heart is partially or completely surrounded by fluid that is seen in all views and the thickness of the fluid as observed by prenatal ultrasound is above age-dependent norms.
Fetal chylothorax
MedGen UID:
1814192
Concept ID:
C5676614
Pathologic Function
The presence of chyle (a type of lipid-rich lymph) in the pleural space (the space surrounding the lung) as observed in a fetus.

Professional guidelines

PubMed

Sharma P, Shaheen NJ, Katzka D, Bergman JJGHM
Gastroenterology 2020 Feb;158(3):760-769. Epub 2019 Nov 12 doi: 10.1053/j.gastro.2019.09.051. PMID: 31730766
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
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

Ghaffarpour N, Baselga E, Boon LM, Diociaiuti A, Dompmartin A, Dvorakova V, El Hachem M, Gasparella P, Haxhija E, Kyrklund K, Irvine AD, Kapp FG, Rößler J, Salminen P, van den Bosch C, van der Vleuten C, Kool LS, Vikkula M
Eur J Med Genet 2022 Dec;65(12):104637. Epub 2022 Oct 9 doi: 10.1016/j.ejmg.2022.104637. PMID: 36223836
Pieper CC, Wagenpfeil J, Henkel A, Geiger S, Köster T, Hoss K, Luetkens JA, Hart C, Attenberger UI, Müller A
Sci Rep 2022 Jul 1;12(1):11164. doi: 10.1038/s41598-022-13806-w. PMID: 35778409Free PMC Article
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
Sharma P, Shaheen NJ, Katzka D, Bergman JJGHM
Gastroenterology 2020 Feb;158(3):760-769. Epub 2019 Nov 12 doi: 10.1053/j.gastro.2019.09.051. PMID: 31730766
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

Diagnosis

Parida L
Dig Liver Dis 2022 Dec;54(12):1723-1724. Epub 2022 Jul 13 doi: 10.1016/j.dld.2022.06.026. PMID: 35840486
Zenker M, Edouard T, Blair JC, Cappa M
Arch Dis Child 2022 Dec;107(12):1073-1078. Epub 2022 Mar 4 doi: 10.1136/archdischild-2021-322858. PMID: 35246453Free PMC Article
Khan TA, Revah O, Gordon A, Yoon SJ, Krawisz AK, Goold C, Sun Y, Kim CH, Tian Y, Li MY, Schaepe JM, Ikeda K, Amin ND, Sakai N, Yazawa M, Kushan L, Nishino S, Porteus MH, Rapoport JL, Bernstein JA, O'Hara R, Bearden CE, Hallmayer JF, Huguenard JR, Geschwind DH, Dolmetsch RE, Paşca SP
Nat Med 2020 Dec;26(12):1888-1898. Epub 2020 Sep 28 doi: 10.1038/s41591-020-1043-9. PMID: 32989314Free PMC Article
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
Sadick M, Müller-Wille R, Wildgruber M, Wohlgemuth WA
Rofo 2018 Sep;190(9):825-835. Epub 2018 Jun 6 doi: 10.1055/a-0620-8925. PMID: 29874693

Therapy

Wiegand S, Dietz A, Wichmann G
Eur Arch Otorhinolaryngol 2022 Aug;279(8):3801-3810. Epub 2022 May 8 doi: 10.1007/s00405-022-07378-8. PMID: 35526176Free PMC Article
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
Sharma P, Shaheen NJ, Katzka D, Bergman JJGHM
Gastroenterology 2020 Feb;158(3):760-769. Epub 2019 Nov 12 doi: 10.1053/j.gastro.2019.09.051. PMID: 31730766
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
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

Prognosis

Triana P, López-Gutierrez JC
Pediatr Blood Cancer 2021 Mar;68(3):e28867. Epub 2020 Dec 27 doi: 10.1002/pbc.28867. PMID: 33369022
Rasmussen JC, Zhu B, Morrow JR, Aldrich MB, Sahihi A, Harlin SA, Fife CE, O'Donnell TF Jr, Sevick-Muraca EM
J Vasc Surg Venous Lymphat Disord 2021 May;9(3):720-730.e2. Epub 2020 Sep 22 doi: 10.1016/j.jvsv.2020.09.007. PMID: 32977070Free PMC Article
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
Li J, Zhong W, Geng X, Liu X, Zhang X, Wang Y, Li H
BMC Pediatr 2020 Sep 19;20(1):441. doi: 10.1186/s12887-020-02337-w. PMID: 32950065Free PMC Article
Cheng J
J Pediatr Surg 2015 Dec;50(12):2143-6. Epub 2015 Sep 4 doi: 10.1016/j.jpedsurg.2015.08.051. PMID: 26421368

Clinical prediction guides

Drmic IE, MacKinnon Modi B, McConnell B, Jilderda S, Hoang N, Noor A, Bassett AS, Speevak M, Stavropoulos DJ, Carter MT
Am J Med Genet A 2022 Oct;188(10):2999-3008. Epub 2022 Jul 28 doi: 10.1002/ajmg.a.62916. PMID: 35899837
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
Davies RW, Fiksinski AM, Breetvelt EJ, Williams NM, Hooper SR, Monfeuga T, Bassett AS, Owen MJ, Gur RE, Morrow BE, McDonald-McGinn DM, Swillen A, Chow EWC, van den Bree M, Emanuel BS, Vermeesch JR, van Amelsvoort T, Arango C, Armando M, Campbell LE, Cubells JF, Eliez S, Garcia-Minaur S, Gothelf D, Kates WR, Murphy KC, Murphy CM, Murphy DG, Philip N, Repetto GM, Shashi V, Simon TJ, Suñer DH, Vicari S, Scherer SW; International 22q11.2 Brain and Behavior Consortium, Bearden CE, Vorstman JAS
Nat Med 2020 Dec;26(12):1912-1918. Epub 2020 Nov 9 doi: 10.1038/s41591-020-1103-1. PMID: 33169016Free PMC Article
Burke S, Maramaldi P
Fetal Pediatr Pathol 2017 Feb;36(1):33-41. Epub 2016 Oct 12 doi: 10.1080/15513815.2016.1231248. PMID: 27732116
Cheng J
J Pediatr Surg 2015 Dec;50(12):2143-6. Epub 2015 Sep 4 doi: 10.1016/j.jpedsurg.2015.08.051. PMID: 26421368

Recent systematic reviews

Wiegand S, Dietz A, Wichmann G
Eur Arch Otorhinolaryngol 2022 Aug;279(8):3801-3810. Epub 2022 May 8 doi: 10.1007/s00405-022-07378-8. PMID: 35526176Free PMC Article
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
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
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
Cheng J
J Pediatr Surg 2015 Dec;50(12):2143-6. Epub 2015 Sep 4 doi: 10.1016/j.jpedsurg.2015.08.051. PMID: 26421368

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