An additional patient with SMAD4-Juvenile Polyposis-Hereditary hemorrhagic telangiectasia and connective tissue abnormalities: SMAD4 loss-of-function and gain-of-function pathogenic variants result in contrasting phenotypes.
Connective Tissue
Cryptorchidism
Facies
Gain of Function Mutation
Growth Disorders
Hand Deformities, Congenital
Humans
Intellectual Disability
Intestinal Polyposis
/ congenital
Mutation
Neoplastic Syndromes, Hereditary
Phenotype
Smad4 Protein
/ genetics
Telangiectasia, Hereditary Hemorrhagic
/ complications
Myhre syndrome
aortic dilation
hypermobility
mitral valve prolapse
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
04
07
2022
received:
10
04
2022
accepted:
11
07
2022
pubmed:
24
7
2022
medline:
15
9
2022
entrez:
23
7
2022
Statut:
ppublish
Résumé
Loss-of-function pathogenic variants in somatic and germline cells in SMAD4 may cause cancer and juvenile polyposis-Hereditary Hemorrhagic Telangiectasia (SMAD4-JP-HHT), respectively. In a similar manner, gain-of-function somatic and germline pathogenic variants in SMAD4 can cause various forms of cancer as well as Myhre syndrome. The different SMAD4 molecular mechanisms result in contrasting clinical phenotypes demonstrated by SMAD4-JP-HHT and Myhre syndrome. We report an additional patient with SMAD4-JP-HHT and aortopathy, and expand the phenotype to include severe valvulopathy, cutaneous, ophthalmologic, and musculoskeletal features consistent with an inherited disorder of connective tissue. We compared this 70-year-old man with SMAD4-JP-HHT to 18 additional literature cases, and also compared patients with SMAD4-JP-HHT to those with Myhre syndrome. In contrast to aorta dilation, hypermobility, and loose skin in SMAD4-JP-HHT, Myhre syndrome has aorta hypoplasia, stiff joints, and firm skin representing an intriguing phenotypic contrast, which can be attributed to different molecular mechanisms involving SMAD4. We remind clinicians about the possibility of significant cardiac valvulopathy and aortopathy, as well as connective tissue disease in SMAD4-JP-HHT. Additional patients and longer follow-up will help determine if more intensive surveillance improves care amongst these patients.
Identifiants
pubmed: 35869926
doi: 10.1002/ajmg.a.62915
doi:
Substances chimiques
SMAD4 protein, human
0
Smad4 Protein
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
3084-3088Informations de copyright
© 2022 Wiley Periodicals LLC.
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