Telangiectasia, Hereditary Hemorrhagic, Type 4 (HHT4)

Categories: Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Neuronal diseases, Rare diseases, Respiratory diseases, Skin diseases

Aliases & Classifications for Telangiectasia, Hereditary Hemorrhagic, Type 4

MalaCards integrated aliases for Telangiectasia, Hereditary Hemorrhagic, Type 4:

Name: Telangiectasia, Hereditary Hemorrhagic, Type 4 57 13 70
Hht4 57 20
Hereditary Hemorrhagic Telangiectasia Type 4 20



57 (Updated 05-Apr-2021)
autosomal dominant

genetic heterogeneity (see hht1, )


telangiectasia, hereditary hemorrhagic, type 4:
Inheritance autosomal dominant inheritance heterogeneous


External Ids:

OMIM® 57 610655
OMIM Phenotypic Series 57 PS187300
MedGen 41 C1857688
UMLS 70 C1857688

Summaries for Telangiectasia, Hereditary Hemorrhagic, Type 4

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 774 Definition An inherited disorder of angiogenesis characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Epidemiology The prevalence is approximately 1/6,000 Clinical description The most common clinical signs of hereditary hemorrhagic telangiectasia (HHT) include recurrent epistaxis (nosebleeds), frequently from childhood, and cutaneous or mucosal telangiectases generally presenting later, and increasing with age, where anemia may become an important part of the disease. Visceral arteriovenous malformations (AVMs) are usually asymptomatic but can lead to complications that produce highly variable manifestations. The age of onset of AVM-related complications is variable, ranging from childhood to geriatric age, with a few cases reported during the neonatal period. Pulmonary AVMs may manifest with brain abscesses, strokes, transient ischemic attacks, signs of chronic hypoxaemia or, rarely, haemorrhagic rupture. AVMs of the central nervous system can be haemorrhagic or, rarely, produce signs of slow compression. Hepatic AVMs, which can remain latent for a long time, in a limited proportion of patients become severe leading to high-output cardiac failure, portal hypertension, pulmonary hypertension or ischemic cholangitis. Hemorrhagic digestive telangiectases increase with age and can worsen chronic anemia. Etiology This genetic disorder is due to pathogenic variants primarily in ENG (9q34.11) or ACVRL1 (12q13.13), encoding proteins involved in vascular development and angiogenic homeostasis of capillaries. Mutations in SMAD4 (18q21.2) occur in rare cases (1-3%) and result in HHT associated with juvenile polyposis. In a small proportion of HHT families, the pathogenic gene variant has not yet been identified. Diagnostic methods The diagnosis is clinical and/or molecular. The clinical diagnosis is based on having at least three of the four Curacao criteria: recurrent epistaxis, cutaneous/mucosal telangiectases, visceral involvement, and a first line family member with HHT. Genetic testing can be used to screen, to confirm a diagnosis, or to rule out the diagnosis if the pathogenic variant is known in the family. Differential diagnosis The differential diagnosis includes limited cutaneous systemic sclerosis, digestive angiodysplasias, isolated sporadic AVMs in the lungs, liver and brain, other vascular anomaly syndromes that cause AVMs; benign hereditary telangiectasia; and other causes of recurrent epistaxis (coagulation disorders or other local nasal factors). Antenatal diagnosis Prenatal genetic testing is possible in families where the pathogenic variant has been identified in the family, but is not necessary for proper pregnancy and delivery management. Decisions about prenatal genetic testing are the choice of the parents, but discussion of all related issues is appropriate. The usual antenatal scans will be offered, and sonographers aware of the presence of HHT in the family will detect most major AVMs. Genetic counseling Transmission is autosomal dominant. Penetrance is age dependent, the majority having symptoms before 50 years of age. The phenotype is highly variable, even between members of the same family. Management and treatment Disease management includes prevention and treatment of epistaxis and anaemia, screening for AVMs, and guidance regarding pregnancy-related issues. The management of pulmonary AVM(s) relies on early detection, occlusion where feasible, and ongoing care in cases of persistent pulmonary AVMs. For severe liver involvement, multidisciplinary patient assessment in a center with expertise in HHT is recommended. Usually, cerebral AVMs that have not bled are not treated, whereas cerebral AVMs that have already bled or have become symptomatic usually require treatment. Gastrointestinal telangiectases may sometimes be the cause of significant anemia, especially in older patients, and need specific management. Awareness of the possibility of AVMs/HHT is important for optimal management of diverse medical states. HHT due to a SMAD4 pathogenic variant requires polyposis screening and aortic follow up. Prognosis Life expectancy is reduced in unscreened patients. In patients assessed and treated for pulmonary AVMs in an HHT Center, life expectancy is comparable to the general population. Pregnancy-related death has been reported, and is a particular risk for women with pulmonary arteriovenous malformations.

MalaCards based summary : Telangiectasia, Hereditary Hemorrhagic, Type 4, is also known as hht4, and has symptoms including dyspnea and cyanosis. An important gene associated with Telangiectasia, Hereditary Hemorrhagic, Type 4 is HHT4 (Telangiectasia, Hereditary Hemorrhagic, Type 4). Affiliated tissues include liver, tongue and heart, and related phenotypes are conjunctival telangiectasia and dyspnea

More information from OMIM: 610655 PS187300

Related Diseases for Telangiectasia, Hereditary Hemorrhagic, Type 4

Symptoms & Phenotypes for Telangiectasia, Hereditary Hemorrhagic, Type 4

Human phenotypes related to Telangiectasia, Hereditary Hemorrhagic, Type 4:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 conjunctival telangiectasia 31 HP:0000524
2 dyspnea 31 HP:0002094
3 transient ischemic attack 31 HP:0002326
4 migraine 31 HP:0002076
5 subarachnoid hemorrhage 31 HP:0002138
6 cerebral hemorrhage 31 HP:0001342
7 cyanosis 31 HP:0000961
8 arteriovenous fistulas of celiac and mesenteric vessels 31 HP:0002642
9 cerebral arteriovenous malformation 31 HP:0002408
10 spinal arteriovenous malformation 31 HP:0002390
11 lip telangiectasia 31 HP:0000214
12 ischemic stroke 31 HP:0002140
13 high-output congestive heart failure 31 HP:0001722
14 spontaneous, recurrent epistaxis 31 HP:0004406
15 pulmonary arteriovenous malformation 31 HP:0006548
16 right-to-left shunt 31 HP:0001694
17 dilatation of mesenteric artery 31 HP:0011934
18 tongue telangiectasia 31 HP:0000227
19 nasal mucosa telangiectasia 31 HP:0000434
20 venous varicosities of celiac and mesenteric vessels 31 HP:0002626
21 palate telangiectasia 31 HP:0002707
22 dilatation of celiac artery 31 HP:0100858

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)

Respiratory Lung:
pulmonary arteriovenous malformation (pavm), especially lower lobes

Cardiovascular Heart:
high-output congestive heart failure
right-to-left shunt

Head And Neck Nose:
spontaneous, recurrent epistaxis (onset childhood)
nasal mucosa telangiectases

Skin Nails Hair Skin:
telangiectases (especially on tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips)

Neurologic Central Nervous System:
transient ischemic attack
subarachnoid hemorrhage
cerebral arteriovenous malformation
spinal arteriovenous malformation
ischemic stroke
Cardiovascular Vascular:
arteriovenous fistulas of celiac and mesenteric vessels
venous varicosities of celiac and mesenteric vessels
arterial aneurysm of celiac and mesenteric vessels

Head And Neck Eyes:
conjunctival telangiectases

Head And Neck Mouth:
lip telangiectases
tongue telangiectases
palate telangiectases

Clinical features from OMIM®:

610655 (Updated 05-Apr-2021)

UMLS symptoms related to Telangiectasia, Hereditary Hemorrhagic, Type 4:

dyspnea; cyanosis

Drugs & Therapeutics for Telangiectasia, Hereditary Hemorrhagic, Type 4

Search Clinical Trials , NIH Clinical Center for Telangiectasia, Hereditary Hemorrhagic, Type 4

Genetic Tests for Telangiectasia, Hereditary Hemorrhagic, Type 4

Anatomical Context for Telangiectasia, Hereditary Hemorrhagic, Type 4

MalaCards organs/tissues related to Telangiectasia, Hereditary Hemorrhagic, Type 4:

Liver, Tongue, Heart

Publications for Telangiectasia, Hereditary Hemorrhagic, Type 4

Articles related to Telangiectasia, Hereditary Hemorrhagic, Type 4:

# Title Authors PMID Year
A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7. 57 61
16969873 2006
Fine mapping of the qHTB1-1QTL, which confers heat tolerance at the booting stage, using an Oryza rufipogon Griff. introgression line. 61
31989206 2020
Current Status of Clinical Diagnosis and Genetic Analysis of Hereditary Hemorrhagic Telangiectasia in South Korea: Multicenter Case Series and a Systematic Review. 61
31455059 2019
Cooperation of tumor-derived HBx mutants and p53-249(ser) mutant in regulating cell proliferation, anchorage-independent growth and aneuploidy in a telomerase-immortalized normal human hepatocyte-derived cell line. 61
20017137 2010
Deposition and function of histone H3 variants in Tetrahymena thermophila. 61
16908532 2006

Variations for Telangiectasia, Hereditary Hemorrhagic, Type 4

Expression for Telangiectasia, Hereditary Hemorrhagic, Type 4

Search GEO for disease gene expression data for Telangiectasia, Hereditary Hemorrhagic, Type 4.

Pathways for Telangiectasia, Hereditary Hemorrhagic, Type 4

GO Terms for Telangiectasia, Hereditary Hemorrhagic, Type 4

Sources for Telangiectasia, Hereditary Hemorrhagic, Type 4

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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