Hereditary hemorrhagic telangiectasia (HHT), also known as Osler disease, is an autosomal dominant vascular dysplasia characterized by severe recurrent nasal and gastrointestinal bleeding and cutaneomucosal telangiectases. HHT is often associated with arteriovenous malformations in the pulmonary, hepatic, cerebral, and spinal circulations. The disease arises from defects in TGF-beta signaling. It has been reported that mutations in SMAD4 cause the combined juvenile polyposis and HHT (JPHT) syndrome.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Structural developmental anomalies primarily affecting one body system
Structural developmental anomalies of the circulatory system
LA90 Structural developmental anomalies of the peripheral vascular system
H00533 Hereditary hemorrhagic telangiectasia
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H00533 Hereditary hemorrhagic telangiectasia
Juvenile polyposis syndrome (JPS) is an autosomal dominant condition identified by the presence of multiple benign, non-cancerous polyps called juvenile polyps in the gastrointestinal tract. A germline mutation in the SMAD4 or BMPR1A gene is found in about 50%-60% of patients with JPS. These genes play a role in the BMP/TGF-beta signalling pathway.
Category
Neoplasm
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Benign neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues
Benign non-mesenchymal neoplasms
2E92 Benign neoplasm of digestive organs
H01023 Juvenile polyposis syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H01023 Juvenile polyposis syndrome
Myhre syndrome (MYHRS) is a developmental disorder characterized by reduced growth, generalized muscular hypertrophy, facial dysmorphism, deafness, cognitive deficits, joint stiffness, and skeletal anomalies. Heterozygous missense mutations in SMAD4 cause this disease. SMAD4 plays a pivotal role in the bone morphogenetic pathway and TGF-beta signaling.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2F Syndromes with multiple structural anomalies, without predominant body system involvement
H02102 Myhre syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H02102 Myhre syndrome
Le Goff C, Mahaut C, Abhyankar A, Le Goff W, Serre V, Afenjar A, Destree A, di Rocco M, Heron D, Jacquemont S, Marlin S, Simon M, Tolmie J, Verloes A, Casanova JL, Munnich A, Cormier-Daire V
Title
Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome.
