HHT4
MCID: TLN010
MIFTS: 21

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, 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 58 13 74
Hht4 58 54
Hereditary Hemorrhagic Telangiectasia Type 4 54

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity (see hht1, )


HPO:

33
telangiectasia, hereditary hemorrhagic, type 4:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Telangiectasia, Hereditary Hemorrhagic, Type 4

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 774Disease definitionAn inherited disorder of angiogenesis characterized by mucocutaneous telangiectases and visceral arteriovenous malformations.EpidemiologyThe prevalence is approximately 1/6,000Clinical descriptionThe 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.EtiologyThis 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 methodsThe diagnosis is clinical and/or molecular. The clinical diagnosis is based on having at least three of the four CuraƧao 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 diagnosisThe 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 diagnosisPrenatal 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 counselingTransmission 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 treatmentDisease 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.PrognosisLife 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.Visit the Orphanet disease page for more resources.

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 brain, testes and liver, and related phenotypes are dyspnea and transient ischemic attack

Description from OMIM: 610655

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:

33 (show all 22)
# Description HPO Frequency HPO Source Accession
1 dyspnea 33 HP:0002094
2 transient ischemic attack 33 HP:0002326
3 migraine 33 HP:0002076
4 conjunctival telangiectasia 33 HP:0000524
5 subarachnoid hemorrhage 33 HP:0002138
6 cerebral hemorrhage 33 HP:0001342
7 cyanosis 33 HP:0000961
8 high-output congestive heart failure 33 HP:0001722
9 spontaneous, recurrent epistaxis 33 HP:0004406
10 pulmonary arteriovenous malformation 33 HP:0006548
11 cerebral arteriovenous malformation 33 HP:0002408
12 arteriovenous fistulas of celiac and mesenteric vessels 33 HP:0002642
13 ischemic stroke 33 HP:0002140
14 spinal arteriovenous malformation 33 HP:0002390
15 lip telangiectasia 33 HP:0000214
16 right-to-left shunt 33 HP:0001694
17 venous varicosities of celiac and mesenteric vessels 33 HP:0002626
18 tongue telangiectasia 33 HP:0000227
19 nasal mucosa telangiectasia 33 HP:0000434
20 palate telangiectasia 33 HP:0002707
21 dilatation of mesenteric artery 33 HP:0011934
22 dilatation of celiac artery 33 HP:0100858

Symptoms via clinical synopsis from OMIM:

58
Respiratory:
dyspnea

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

Cardiovascular Vascular:
arteriovenous fistulas of celiac and mesenteric vessels
arterial aneurysm of celiac and mesenteric vessels
venous varicosities of celiac and mesenteric vessels

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
ischemic stroke
spinal arteriovenous malformation
more
Cardiovascular Heart:
high-output congestive heart failure
right-to-left shunt

Head And Neck Eyes:
conjunctival telangiectases

Head And Neck Mouth:
lip telangiectases
tongue telangiectases
palate telangiectases

Clinical features from OMIM:

610655

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:

42
Brain, Testes, Liver, Tongue, Skin, Eye

Publications for Telangiectasia, Hereditary Hemorrhagic, Type 4

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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