Myhre syndrome with facial paralysis and branch pulmonary stenosis

Hawkes, Lara; Kini, Usha

doi:10.1097/mcd.0000000000000068

“…In this study, three distinct heterozygous missense SMAD4 mutations were identified affecting the codon for Ile500 in 11 individuals with Myhre syndrome [4]. To our knowledge, 58 affected individuals with a molecularly confirmed diagnosis of Myhre syndrome have been reported [1,[4][5][6][7][8][9][10][11][12][13][14][15][16]. The four pathogenic variants reported to date are missense variants p.Ile500Thr, p.Ile500Val, p.Ile500Met and p.A496Cys [1,2,4,11].…”

Section: Introductionmentioning

confidence: 82%

A child with Myhre syndrome presenting with moyamoya disease: a case report and literature review

Zheng

¹

,

Wang

²

,

Huang

³

et al. 2019

Preprint

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Background: Myhre syndrome (MS) is a very rare connective tissue disorder characterized by facial dysmorphism, thickened skin, muscular pseudohypertrophy and joint limitation. Developmental delay is common. But there are no reports of MS combined with moyamoya disease (MMD). Here, we present the first Chinese case of MS complicated with MMD. Case presentation: A 7-old-year girl presented with developmental disorder, short stature, brachydactyly, short stature, and intellectual deficiency with behavioral problems. We sequenced SMAD4 using exome sequencing and identified a denovo mutation (p.Ile500Thr) in the patient. In addition, The patient also had recurrent hemiplegia and seizures was diagnosed with definitive MMD by digital subtraction angiography (DSA) according to the diagnostic criteria. Conclusions: MMD has never been described in the individual with the clinical presentation of MS. we present an unusual association of MS with a typical moyamoya syndrome in a young girl who developed recurrent hemiplegia and seizure in an effort to explore whether MS may contribute to the MMD.

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“…The first case of MS was reported in 1981 ( 2 ). To date, 90 confirmed cases have been reported, with the youngest patient being 23 months old ( 3 ). Clinical manifestations include short stature, intrauterine growth restriction, dysmorphic facial features (blepharoptosis, prognathism, and small ears among others), varying degrees of cognitive impairment, decreased joint mobility, skin stiffness, and hearing impairment.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Improved Height in a Patient With Myhre Syndrome Using a Combination of Growth Hormone and Letrozole

Wu

¹

,

Wang

²

,

Cui

³

et al. 2021

Front. Pediatr.

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Myhre syndrome is a rare disorder caused by a heterozygous mutation in the SMAD4 gene. Affected patients may exhibit dysmorphic facial features, intrauterine growth retardation, short stature, obesity, muscle hypertrophy, thickened skin, limited joint movement, hearing impairment, and varying degrees of psychomotor developmental disorder. Serious complications of the cardiovascular and respiratory system may be seen later in life. We report the case of a Chinese boy with Myhre syndrome presenting with a novel symptom of giant testicles where treatment with growth hormone combined with letrozole successfully improved his short stature. This case shows that letrozole combined with growth hormone can improve height in children with Myhre syndrome without adverse effects.

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Molecular Genetics of M yhre Syndrome

Michot

¹

,

Goff

²

,

Cormier‐Daire

³

2016

Encyclopedia of Life Sciences

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Myhre syndrome (MIM 139210) is a rare autosomal‐dominant disorder characterised by short stature, brachydactyly, facial dysmorphism (short palpebral fissures, prognathism and short philtrum), developmental delay with mental retardation or/and behavioural troubles, progressive deafness of mixed conductive and sensory type and a trio of thickened skin, generalised muscle hypertrophy and restricted joint mobility. Life‐threatening complications (obesity, arterial hypertension and bronchopulmonary insufficiency) are observed in the course of the disease leading to an early death. In 2011, SMAD4 (SMAD family member 4) has been identified as the disease‐causing gene. All mutations identified so far are de novo heterozygous missense mutations, mainly involving Ile500. While SMAD4 inactivation is reported in juvenile polyposis syndrome with increased colorectal cancer risk, no increased tumoural risk has been observed in Myhre syndrome. SMAD4 is a key mediator of TGF‐β (transforming growth factor beta)/BMP (bone morphogenetic protein) signalling and the understanding of the consequences of SMAD4 mutations during development will decipher new regulatory network related to TGF‐β/BMP signalling. Key Concepts Myhre syndrome is a rare genetic condition of autosomal‐dominant inheritance due to SMAD4 mutations affecting Arg496 or Ile500 residues. Myhre syndrome is characterised by short stature, brachydactyly, facial dysmorphism, developmental delay, progressive deafness and a trio of thickened skin, generalised muscle hypertrophy and restricted joint mobility. Myhre syndrome is associated to a risk of early death due to possibly life‐threatening health conditions (obesity, arterial hypertension, bronchopulmonary insufficiency, laryngotracheal stenosis and pericarditis). Similar to mothers against decapentaplegic family member 4 ( SMAD4 ) encodes the common partner SMAD of the eight‐member family of SMAD proteins. SMAD4 aggregates into heterotrimer with the receptor‐regulated SMADs (R‐SMADs) once they are activated by phosphorylation by transmembrane serine–threonine receptor kinases in response to stimulation of TGF‐β, activin or BMP receptor pathways. The SMAD4 mutations identified in Myhre syndrome are expected to disturb the monoubiquitination of SMAD4 which occurs at Lys519 and also to disturb the function of the SMAD heterotrimer which regulates the expression of target genes. Germline heterozygous mutations in SMAD4 are known to cause juvenile polyposis syndrome (JPS) and JPS‐hereditary hemorrhagic telangiectasia. The SMAD4 mutations observed in JPS and JPS‐HHT include nonsense, missense, splice‐site changes and deletions, consistent with a loss‐of‐function mechanism. Increased tumoural risk has not been observed so far in Myhre syndrome. The development of tissue‐specific mouse models of Smad4 deficiency further highlighted the important role of Smad4 in a wide range of embryonic developmental processes.

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Myhre syndrome with facial paralysis and branch pulmonary stenosis

Cited by 12 publications

References 7 publications

A child with Myhre syndrome presenting with moyamoya disease: a case report and literature review

A child with Myhre syndrome presenting with moyamoya disease: a case report and literature review

Case Report: Improved Height in a Patient With Myhre Syndrome Using a Combination of Growth Hormone and Letrozole

Molecular Genetics of M yhre Syndrome

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