Lack of resemblance between Myhre syndrome and other “segmental progeroid” syndromes warrants restraint in applying this classification

Lin, Angela E.; Brunetti‐Pierri, Nicola; Callewaert, Bert; Cormier‐Daire, Valérie; Douzgou, Sofia; Kinane, T. Bernard; Lindsay, Mark E.; Starr, Lois J.

doi:10.1007/s11357-021-00337-x

Cited by 1 publication

(2 citation statements)

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“…Heterozygous SMAD4 c.1499T>C (p.Ile500Thr) is a known gain‐of‐function mutation, which was demonstrated to increase SMAD4 stability and impaired transforming growth factor beta (TGF‐beta) mediated transcriptional control in fibroblasts isolated from Myhre syndrome patients. Such a gain‐of‐function mutation is in contrast to other SMAD4 loss‐of‐function variants, preferably through preventing homo‐and/or‐hetero‐oligomerization with other SMAD proteins, and is associated with a loss of tumor suppressive roles in carcinogenesis 1–3 . Most patients have intellectual disability and growth abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…Such a gain-of-function mutation is in contrast to other SMAD4 loss-of-function variants, preferably through preventing homo-and/or-hetero-oligomerization with other SMAD proteins, and is associated with a loss of tumor suppressive roles in carcinogenesis. [1][2][3] Most patients have intellectual disability and growth abnormalities. Hearing loss, visual problem, midface hypoplasia and thick skin could present in more than half of the patients.…”

Section: Pregnancy Outcomes and Neonatal Findingsmentioning

confidence: 99%

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Prenatal diagnosis of Myhre syndrome with a heterozygous pathogenic variant in SMAD4 gene presented with thick nuchal translucency and cardiac abnormalities

Hui,

Mok,

Luk

et al. 2023

Prenatal Diagnosis

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Prenatal testing was performed in a 39‐year‐old Chinese pregnant woman referred for increased nuchal translucency measuring 5.7 mm. Non‐invasive prenatal testing and SNP array study on amniotic fluid samples were normal. Whole exome sequencing (WES) was initiated further as the fetus had pericardial effusion of 1.2 mm, thickened myocardium over the right ventricular lateral wall and aberrant right subclavian artery. A detailed fetal echocardiogram also revealed persistent left superior vena cava and dilated coronary sinus at 20 weeks. From whole exome sequencing of the trio, a de novo heterozygous variant NM_005359.5(SMAD4): c.1499T>C (p.Ile500Thr) was detected. This pathogenic variant has been reported in the postnatal case cohort of Myhre syndrome. This condition is characterized by facial dysmorphism, intellectual disability, hearing loss, skeletal abnormalities and potential life threatening respiratory or cardiovascular manifestations. Termination of pregnancy was performed at 23 weeks. Small chins, pre‐axial polydactyly, brachydactyly and clinodactyly were noted in the abortus. Ultrasound findings of increased nuchal translucency, thickened myocardium and pericardial effusion prompted further genetic evaluation for the prenatal diagnosis of Myhre syndrome by whole exome sequencing.

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Section: Discussionmentioning

confidence: 99%

Section: Pregnancy Outcomes and Neonatal Findingsmentioning

confidence: 99%