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Hennekam lymphangiectasia-lymphedema syndrome 3(HKLLS3)

MedGen UID:
1648368
Concept ID:
C4748408
Disease or Syndrome
Synonyms: HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME 3; HKLLS3
 
Gene (location): ADAMTS3 (4q13.3)
 
Monarch Initiative: MONDO:0032564
OMIM®: 618154

Definition

Hennekam lymphangiectasia-lymphedema syndrome-3 (HKKLLS3) is characterized by widespread congenital edema that is more severe in more dependent areas of the body. Associated features include facial dysmorphism and protein-losing enteropathy of variable severity (Brouillard et al., 2017). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510). [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.
Protein-losing enteropathy
MedGen UID:
19522
Concept ID:
C0033680
Disease or Syndrome
Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption. Some patients also exhibit bowel inflammation, recurrent infections associated with hypogammaglobulinemia, and/or angiopathic thromboembolic disease. Patient T lymphocytes show increased complement activation, causing surface deposition of complement and generating soluble C5a (Ozen et al., 2017).
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.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Facial edema
MedGen UID:
154241
Concept ID:
C0542571
Pathologic Function
Swelling due to an excessive accumulation of fluid in facial tissues.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Professional guidelines

PubMed

Shinwari K, Wu Y, Rehman HM, Xiao N, Bolkov M, Tuzankina I, Chereshnev V
BMC Bioinformatics 2023 Jun 15;24(1):251. doi: 10.1186/s12859-023-05361-6. PMID: 37322437Free PMC Article

Recent clinical studies

Etiology

Shinwari K, Wu Y, Rehman HM, Xiao N, Bolkov M, Tuzankina I, Chereshnev V
BMC Bioinformatics 2023 Jun 15;24(1):251. doi: 10.1186/s12859-023-05361-6. PMID: 37322437Free PMC Article
Jones GE, Mansour S
Clin Med (Lond) 2017 Dec;17(6):552-557. doi: 10.7861/clinmedicine.17-6-552. PMID: 29196357Free PMC Article

Diagnosis

Shinwari K, Wu Y, Rehman HM, Xiao N, Bolkov M, Tuzankina I, Chereshnev V
BMC Bioinformatics 2023 Jun 15;24(1):251. doi: 10.1186/s12859-023-05361-6. PMID: 37322437Free PMC Article
Fattorusso A, Pieri ES, Dell'Isola GB, Prontera P, Mencaroni E, Stangoni G, Esposito S
Medicine (Baltimore) 2020 Jul 2;99(27):e20995. doi: 10.1097/MD.0000000000020995. PMID: 32629717Free PMC Article
Boone PM, Paterson S, Mohajeri K, Zhu W, Genetti CA, Tai DJC, Nori N, Agrawal PB, Bacino CA, Bi W, Talkowski ME, Hogan BM, Rodan LH
Am J Med Genet A 2020 Jan;182(1):189-194. Epub 2019 Oct 21 doi: 10.1002/ajmg.a.61392. PMID: 31633297Free PMC Article
Scheuerle AE, Sweed NT, Timmons CF, Smith ED, Alcaraz WA, Shinde DN
Am J Med Genet A 2018 Dec;176(12):2858-2861. Epub 2018 Nov 18 doi: 10.1002/ajmg.a.40633. PMID: 30450763
Jones GE, Mansour S
Clin Med (Lond) 2017 Dec;17(6):552-557. doi: 10.7861/clinmedicine.17-6-552. PMID: 29196357Free PMC Article

Prognosis

Shinwari K, Wu Y, Rehman HM, Xiao N, Bolkov M, Tuzankina I, Chereshnev V
BMC Bioinformatics 2023 Jun 15;24(1):251. doi: 10.1186/s12859-023-05361-6. PMID: 37322437Free PMC Article
Fattorusso A, Pieri ES, Dell'Isola GB, Prontera P, Mencaroni E, Stangoni G, Esposito S
Medicine (Baltimore) 2020 Jul 2;99(27):e20995. doi: 10.1097/MD.0000000000020995. PMID: 32629717Free PMC Article
Brouillard P, Dupont L, Helaers R, Coulie R, Tiller GE, Peeden J, Colige A, Vikkula M
Hum Mol Genet 2017 Nov 1;26(21):4095-4104. doi: 10.1093/hmg/ddx297. PMID: 28985353

Clinical prediction guides

Shinwari K, Wu Y, Rehman HM, Xiao N, Bolkov M, Tuzankina I, Chereshnev V
BMC Bioinformatics 2023 Jun 15;24(1):251. doi: 10.1186/s12859-023-05361-6. PMID: 37322437Free PMC Article
Fattorusso A, Pieri ES, Dell'Isola GB, Prontera P, Mencaroni E, Stangoni G, Esposito S
Medicine (Baltimore) 2020 Jul 2;99(27):e20995. doi: 10.1097/MD.0000000000020995. PMID: 32629717Free PMC Article
Brouillard P, Dupont L, Helaers R, Coulie R, Tiller GE, Peeden J, Colige A, Vikkula M
Hum Mol Genet 2017 Nov 1;26(21):4095-4104. doi: 10.1093/hmg/ddx297. PMID: 28985353

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