Prenatal Diagnosis of Myhre Syndrome in Two Cases: Further Delineation of the Cardiac and External Phenotype.
Myhre syndrome
NGS
SMAD4
fetal diagnosis
prenatal
Journal
Prenatal diagnosis
ISSN: 1097-0223
Titre abrégé: Prenat Diagn
Pays: England
ID NLM: 8106540
Informations de publication
Date de publication:
08 Aug 2024
08 Aug 2024
Historique:
revised:
20
07
2024
received:
17
04
2024
accepted:
22
07
2024
medline:
9
8
2024
pubmed:
9
8
2024
entrez:
8
8
2024
Statut:
aheadofprint
Résumé
Myhre syndrome is a rare genetic disease caused by recurrent gain-of-function variants in SMAD4 (Ile500Thr, Ile500Val, Arg496Cys, and Ile500Met) characterized by postnatal short stature with pseudo-muscular build, joint stiffness, variable intellectual disability, hearing loss, and a distinctive pattern of dysmorphic facial features. The course can be severe in some cases, with life-threatening cardiac and pulmonary complications caused by connective tissue involvement. These progressive features over time make early clinical diagnosis difficult but possible by astute clinicians who evaluate young children with autism or short stature and unusual appearance. Only two cases of Myhre syndrome diagnosed during the prenatal period have been reported. Here, we present a detailed description of two unrelated fetuses with Myhre syndrome, each molecularly confirmed by genome or exome sequencing, who underwent fetal examination after termination of pregnancy. One had severe intrauterine growth retardation associated with crossed fused renal ectopia, and the other one had pulmonary atresia with ventricular septal defect (a form of tetralogy of Fallot). Both had mild dysmorphic features with a wide nasofrontal angle. Our results and a systematic prenatal literature review add insight into the early natural history of Myhre syndrome and highlight the contribution of prenatal next-generation sequencing in prenatal diagnosis and the importance of fetal autopsy in Myhre syndrome.
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : University Hospital of Dijon
Organisme : French Ministry of Health: PHRC Interrégional DPNI-exome
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
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V. Caputo, L. Cianetti, M. Niceta, et al., “A Restricted Spectrum of Mutations in the SMAD4 Tumor‐Suppressor Gene Underlies Myhre Syndrome,” American Journal of Human Genetics 90, no. 1 (2012): 161–169, https://doi.org/10.1016/j.ajhg.2011.12.011.
D. D. Yang, M. Rio, C. Michot, et al., “Natural History of Myhre Syndrome,” Orphanet Journal of Rare Diseases 17, no. 1 (2022): 304, https://doi.org/10.1186/s13023‐022‐02447‐x.
A. E. Lin, E. R. Scimone, R. P. Thom, et al., “Emergence of the Natural History of Myhre Syndrome: 47 Patients Evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016–2023),” American Journal of Medical Genetics, Part A (2024): e63638, Published ahead of print. https://doi.org/10.1002/ajmg.a.63638.
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L. J. Starr, M. E. Lindsay, D. Perry, et al., “Review of the Pathologic Characteristics in Myhre Syndrome: Gain‐of‐Function Pathogenic Variants in SMAD4 Cause a Multisystem Fibroproliferative Response,” Pediatric and Developmental Pathology 25, no. 6 (2022): 611–623, https://doi.org/10.1177/10935266221079569.