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Lymphatic malformation 7(LMPHM7)

MedGen UID:
934596
Concept ID:
C4310629
Disease or Syndrome
Synonyms: Hydrops fetalis, nonimmune, and/or atrial septal defect, susceptibility to; LMPHM7
 
Gene (location): EPHB4 (7q22.1)
 
Monarch Initiative: MONDO:0015009
OMIM®: 617300

Definition

LMPHM7 is an autosomal dominant disorder with variable expressivity. Some patients may develop severe nonimmune lymphatic-related hydrops fetalis (LRHF) in utero, resulting in early death, whereas others may have milder manifestations, such as atrial septal defect (ASD) or varicose veins as adults. The hydrops and/or swelling improves spontaneously in those who survive the neonatal period (summary by Martin-Almedina et al., 2016). For a discussion of genetic heterogeneity of lymphatic malformation, see 153100. [from OMIM]

Clinical features

From HPO
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Pericardial effusion
MedGen UID:
10653
Concept ID:
C0031039
Disease or Syndrome
Accumulation of fluid within the pericardium.
Varicose disease
MedGen UID:
21827
Concept ID:
C0042345
Disease or Syndrome
Enlarged and tortuous veins.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity (between the layers of the peritoneum that lines the abdomen).
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Chylothorax
MedGen UID:
40305
Concept ID:
C0008733
Disease or Syndrome
Accumulation of excessive amounts of lymphatic fluid (chyle) in the pleural cavity.
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Pathologic Function
The presence of an excessive amount of fluid in the pleural cavity.
Pulmonary edema
MedGen UID:
11026
Concept ID:
C0034063
Pathologic Function
Fluid accumulation in the lungs.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Lymphedema
MedGen UID:
6155
Concept ID:
C0024236
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
Facial edema
MedGen UID:
154241
Concept ID:
C0542571
Pathologic Function
Swelling due to an excessive accumulation of fluid in facial tissues.
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).
Increased nuchal translucency
MedGen UID:
869253
Concept ID:
C4023676
Finding
Nuchal translucency is the sonographic appearance of subcutaneous accumulation of liquid in the back of the fetal neck in the first trimester of pregnancy (11-14 gestational weeks of pregnancy).

Professional guidelines

PubMed

Jablonski SA, Mazepa ASW, Tolbert MK
J Vet Intern Med 2024 Jan-Feb;38(1):145-151. Epub 2023 Dec 1 doi: 10.1111/jvim.16966. PMID: 38038236Free PMC Article
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
Bertino F, Trofimova AV, Gilyard SN, Hawkins CM
Pediatr Radiol 2021 Jun;51(7):1162-1184. Epub 2021 Apr 16 doi: 10.1007/s00247-021-04968-2. PMID: 33860862

Recent clinical studies

Etiology

Jablonski SA, Mazepa ASW, Tolbert MK
J Vet Intern Med 2024 Jan-Feb;38(1):145-151. Epub 2023 Dec 1 doi: 10.1111/jvim.16966. PMID: 38038236Free PMC Article
Zwerink L, Praster R, van der Vleuten C
Phlebology 2021 Aug;36(7):549-554. Epub 2021 Jan 26 doi: 10.1177/0268355521989873. PMID: 33499729
Wen Z, Tong G, Liu Y
Clin Nucl Med 2021 Jan;46(1):25-30. doi: 10.1097/RLU.0000000000003361. PMID: 33156055
Barclay SF, Inman KW, Luks VL, McIntyre JB, Al-Ibraheemi A, Church AJ, Perez-Atayde AR, Mangray S, Jeng M, Kreimer SR, Walker L, Fishman SJ, Alomari AI, Chaudry G, Trenor Iii CC, Adams D, Kozakewich HPW, Kurek KC
Genet Med 2019 Jul;21(7):1517-1524. Epub 2018 Dec 13 doi: 10.1038/s41436-018-0390-0. PMID: 30542204Free PMC Article
Manjaly JG, Alexander VR, Pepper CM, Ifeacho SN, Hewitt RJ, Hartley BE
Int J Pediatr Otorhinolaryngol 2015 Jul;79(7):1007-12. Epub 2015 Apr 22 doi: 10.1016/j.ijporl.2015.04.012. PMID: 25921075

Diagnosis

Rosenberg TL, Phillips JD
Otolaryngol Clin North Am 2022 Dec;55(6):1215-1231. doi: 10.1016/j.otc.2022.07.019. PMID: 36371136
Klosterman T, O TM
Otolaryngol Clin North Am 2018 Feb;51(1):213-223. doi: 10.1016/j.otc.2017.09.013. PMID: 29217064
Manjaly JG, Alexander VR, Pepper CM, Ifeacho SN, Hewitt RJ, Hartley BE
Int J Pediatr Otorhinolaryngol 2015 Jul;79(7):1007-12. Epub 2015 Apr 22 doi: 10.1016/j.ijporl.2015.04.012. PMID: 25921075
Yang SY, Kwon SK, Choi SI
J Gastroenterol Hepatol 2006 Jul;21(7):1215. doi: 10.1111/j.1440-1746.2006.04556.x. PMID: 16824080
Askin DF, Young S
Neonatal Netw 2001 Dec;20(8):7-13. doi: 10.1891/0730-0832.20.8.7. PMID: 12144107

Therapy

Shu W, Wang Y, Deji Z, Li C, Chen C, Ding W, Du P, Wang X
Inflamm Res 2024 Jul;73(7):1157-1172. Epub 2024 May 7 doi: 10.1007/s00011-024-01889-2. PMID: 38713235
Jablonski SA, Mazepa ASW, Tolbert MK
J Vet Intern Med 2024 Jan-Feb;38(1):145-151. Epub 2023 Dec 1 doi: 10.1111/jvim.16966. PMID: 38038236Free PMC Article
Reddy S, Handler SS, Wu S, Rabinovitch M, Wright G
J Am Heart Assoc 2020 Apr 7;9(7):e015871. Epub 2020 Mar 19 doi: 10.1161/JAHA.119.015871. PMID: 32188306Free PMC Article
Thomas DM, Wieck MM, Grant CN, Dossa A, Nowicki D, Stanley P, Zeinati C, Howell LK, Anselmo DM
J Vasc Interv Radiol 2016 Dec;27(12):1846-1856. Epub 2016 Oct 22 doi: 10.1016/j.jvir.2016.08.012. PMID: 27776983
Wang Z, Li K, Yao W, Dong K, Xiao X, Zheng S
Pediatr Blood Cancer 2015 Jul;62(7):1291-3. Epub 2015 Jan 18 doi: 10.1002/pbc.25422. PMID: 25598153

Prognosis

Hammer C, Pierson S, Acevedo A, Goldberg J, Westover T, Chawla D, Mabey B, Muzzey D, Johansen Taber K
Prenat Diagn 2024 Jul;44(8):925-935. Epub 2024 Apr 15 doi: 10.1002/pd.6562. PMID: 38622914
Carragher DJ, Towler A, Mileva VR, White D, Hancock PJB
Cogn Res Princ Implic 2022 Apr 5;7(1):30. doi: 10.1186/s41235-022-00381-x. PMID: 35380315Free PMC Article
Butensky A, de Rinaldis CP, Patel S, Edman S, Bailey A, McGinn DE, Zackai E, Crowley TB, McDonald-McGinn DM, Min J, Goldmuntz E
Am J Med Genet A 2021 Mar;185(3):753-758. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62032. PMID: 33369133
Barclay SF, Inman KW, Luks VL, McIntyre JB, Al-Ibraheemi A, Church AJ, Perez-Atayde AR, Mangray S, Jeng M, Kreimer SR, Walker L, Fishman SJ, Alomari AI, Chaudry G, Trenor Iii CC, Adams D, Kozakewich HPW, Kurek KC
Genet Med 2019 Jul;21(7):1517-1524. Epub 2018 Dec 13 doi: 10.1038/s41436-018-0390-0. PMID: 30542204Free PMC Article
Beaton EA, Qin Y, Nguyen V, Johnson J, Pinter JD, Simon TJ
Psychiatry Res 2010 Feb 28;181(2):108-13. Epub 2010 Jan 13 doi: 10.1016/j.pscychresns.2009.10.009. PMID: 20074913Free PMC Article

Clinical prediction guides

Bhattarai D, McGinn DE, Crowley TB, Giunta V, Gaiser K, Zackai EH, Emanuel BS, Heimall J, Jyonouchi S, Lee J, Sun D, McDonald-McGinn DM, Sullivan KE
J Clin Immunol 2023 May;43(4):794-807. Epub 2023 Feb 3 doi: 10.1007/s10875-023-01443-5. PMID: 36735193Free PMC Article
Mauro J, Diaz M, Córdova T, Villanueva K, Cáceres T, Bassi A, Fritsch R, Repetto GM, Ocampo-Garcés A
Sleep 2022 Feb 14;45(2) doi: 10.1093/sleep/zsab300. PMID: 34962269
Guo T, Diacou A, Nomaru H, McDonald-McGinn DM, Hestand M, Demaerel W, Zhang L, Zhao Y, Ujueta F, Shan J, Montagna C, Zheng D, Crowley TB, Kushan-Wells L, Bearden CE, Kates WR, Gothelf D, Schneider M, Eliez S, Breckpot J, Swillen A, Vorstman J, Zackai E, Benavides Gonzalez F, Repetto GM, Emanuel BS, Bassett AS, Vermeesch JR, Marshall CR, Morrow BE; International Chromosome 22q11.2, International 22q11.2 Brain and Behavior Consortia
Hum Mol Genet 2018 Apr 1;27(7):1150-1163. doi: 10.1093/hmg/ddy028. PMID: 29361080Free PMC Article
Boon LM, Ballieux F, Vikkula M
Clin Plast Surg 2011 Jan;38(1):7-19. doi: 10.1016/j.cps.2010.08.012. PMID: 21095468Free PMC Article
Cavalli LR, Cavaliéri LM, Ribeiro LA, Cavalli IJ, Silveira R, Rogatto SR
Hereditas 1997;126(3):261-8. doi: 10.1111/j.1601-5223.1997.00261.x. PMID: 9350140

Recent systematic reviews

Nzelu D, Panayotidis I, Smith GD, Pandya P
J Ultrasound Med 2024 Dec;43(12):2327-2337. Epub 2024 Sep 9 doi: 10.1002/jum.16566. PMID: 39248487
Dietrich E, Grimaux X, Martin L, Samimi M
Ann Dermatol Venereol 2022 Dec;149(4):228-237. Epub 2022 Oct 11 doi: 10.1016/j.annder.2022.03.011. PMID: 36229262
Scarpazza C, Lattanzi GM, Antoniades M, Di Fabio F, Sartori G, Eickhoff SB, McGuire P, Tognin S
Neurosci Biobehav Rev 2019 Dec;107:143-153. Epub 2019 Sep 4 doi: 10.1016/j.neubiorev.2019.09.004. PMID: 31493414
Homans JF, Tromp IN, Colo D, Schlösser TPC, Kruyt MC, Deeney VFX, Crowley TB, McDonald-McGinn DM, Castelein RM
Am J Med Genet A 2018 Oct;176(10):2104-2120. Epub 2017 Nov 21 doi: 10.1002/ajmg.a.38545. PMID: 29159873
D'Antonio F, Khalil A, Zidere V, Carvalho JS
Ultrasound Obstet Gynecol 2016 Apr;47(4):423-32. Epub 2016 Mar 16 doi: 10.1002/uog.15805. PMID: 26643657

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