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Transplant Infectious Disease : An... Dec 2020
Topics: Cryptorchidism; Facies; Growth Disorders; Hand Deformities, Congenital; Histoplasmosis; Hoarseness; Humans; Intellectual Disability; Kidney Transplantation; Larynx
PubMed: 32510794
DOI: 10.1111/tid.13358 -
Frontiers in Pediatrics 2020Myhre syndrome is a rare condition caused by a mutation in the gene, which leads to a defective TGF-β/BMP signaling, resulting in the proliferation of abnormal fibrous...
Myhre syndrome is a rare condition caused by a mutation in the gene, which leads to a defective TGF-β/BMP signaling, resulting in the proliferation of abnormal fibrous tissues. Clinically, patients with Myhre syndrome manifest with defects of connective tissue (skin, muscles, joints), and cardiovascular and neurological impairment. In our report, we present a case of a 16-year-old female with skeletal abnormalities, reduced articular mobility, skin, and muscular hypertrophy and cardiovascular defects characteristic of Myhre syndrome. Long-term pulmonary hypertension and arterial hypertension were persistent in spite of antihypertensive treatment. Our patient was also diagnosed with chronic kidney disease and Dunbar syndrome, which is an external compression of the coeliac trunk or coeliac artery by the surrounding tissues. Until now, only a few cases of renal complications in Myhre syndrome have been published. We describe for the first time a female patient with genetically confirmed Myhre syndrome caused by the p.Ile500Val mutation presenting with an unusual occurrence of congenital vesicoureteral reflux, proteinuria with a decreased renal function, and a condition recognized as Dunbar syndrome.
PubMed: 32175297
DOI: 10.3389/fped.2020.00072 -
Molecular Syndromology Jan 2020Myhre syndrome is a rare autosomal dominant multisystemic disorder. Typical features of this disorder include distinctive facial appearance, deafness, intellectual...
Myhre syndrome is a rare autosomal dominant multisystemic disorder. Typical features of this disorder include distinctive facial appearance, deafness, intellectual disability, cardiovascular abnormalities, short stature, brachydactyly, and skeletal anomalies. Gain-of-function mutations in the gene are responsible for this syndrome. Herein, we present a 9.6-year-old Turkish girl with molecularly confirmed Myhre syndrome who had novel findings including bilateral Axenfield Rieger anomaly with secondary glaucoma and bilateral enlarged vestibular aqueducts.
PubMed: 32021609
DOI: 10.1159/000504829 -
American Journal of Medical Genetics.... Feb 2020Myhre syndrome is an increasingly diagnosed rare syndrome that is caused by one of two specific heterozygous gain-of-function pathogenic variants in SMAD4. The phenotype...
Myhre syndrome is an increasingly diagnosed rare syndrome that is caused by one of two specific heterozygous gain-of-function pathogenic variants in SMAD4. The phenotype includes short stature, characteristic facial appearance, hearing loss, laryngotracheal stenosis, arthritis, skeletal abnormalities, learning and social challenges, distinctive cardiovascular defects, and a striking fibroproliferative response in the ear canals, airways, and serosal cavities (peritoneum, pleura, pericardium). Confirmation of the clinical diagnosis is usually prompted by the characteristic appearance with developmental delay and autistic-like behavior using targeted gene sequencing or by whole exome sequencing. We describe six patients (two not previously reported) with molecularly confirmed Myhre syndrome and neoplasia. Loss-of-function pathogenic variants in SMAD4 cause juvenile polyposis syndrome and we hypothesize that the gain-of-function pathogenic variants observed in Myhre syndrome may contribute to neoplasia in the patients reported herein. The frequency of neoplasia (9.8%, 6/61) in this series (two new, four reported patients) and endometrial cancer (8.8%, 3/34, mean age 40 years) in patients with Myhre syndrome, raises the possibility of cancer susceptibility in these patients. We alert clinicians to the possibility of detecting this syndrome when cancer screening panels are used. We propose that patients with Myhre syndrome are more susceptible to neoplasia, encourage increased awareness, and suggest enhanced clinical monitoring.
Topics: Adult; Cryptorchidism; Endometrial Neoplasms; Facies; Female; Gain of Function Mutation; Growth Disorders; Hand Deformities, Congenital; Heterozygote; Humans; Intellectual Disability; Male; Middle Aged; Mutation; Neoplasms; Phenotype; Smad4 Protein; Transforming Growth Factor beta; Exome Sequencing
PubMed: 31837202
DOI: 10.1002/ajmg.a.61430 -
Clinica Chimica Acta; International... Jan 2020Myhre syndrome is a rare autosomal dominant multi-organ disorder characterized by growth retardation, skeletal anomalies, muscular hypertrophy, joint stiffness, facial...
Myhre syndrome is a rare autosomal dominant multi-organ disorder characterized by growth retardation, skeletal anomalies, muscular hypertrophy, joint stiffness, facial dysmorphism, deafness, cardiovascular disease, and abnormal sexual development. Here we described the first two Chinese Myhre syndrome patients diagnosed by whole-exome sequencing. They both had de novo c.1498A > G (p.Ile500Val) variant in SMAD4 and presented with key characteristics of Myhre syndrome but also revealed uncommon features (polydactyly in the girl and precocious puberty in the boy). We performed functional analysis on four previously reported SMAD4 pathogenic variants in Myhre syndrome patients using dual-luciferase assay. Our results revealed that the pathogenic variants resulted in a variable degree of increased transcription activity of target genes that contain the minimal SMAD binding elements in their promoter regions. The boy responded to the recombinant human growth hormone treatment with improved height but also led to hyperinsulinemia and advanced bone age. Because of his precocious puberty, we subsequently combined the recombinant human growth hormone and gonadotrophin-releasing hormone agonist treatments, which resulted in overall improved height. We reviewed the sexual features of reported Myhre syndrome cases and discussed the possible mechanism of SMAD4 variants in Myhre syndrome that lead to the abnormal hypothalamic-pituitary-gonadal axis.
Topics: Base Sequence; Child, Preschool; China; Cryptorchidism; Facies; Female; Genetic Variation; Growth Disorders; Hand Deformities, Congenital; Humans; Infant; Intellectual Disability; Male; Pregnancy; Smad4 Protein
PubMed: 31654632
DOI: 10.1016/j.cca.2019.10.006 -
American Journal of Medical Genetics.... Dec 2019Myhre syndrome is a rare multisystem connective tissue disorder, characterized by short stature, facial dysmorphology, variable intellectual disability, skeletal...
Myhre syndrome is a rare multisystem connective tissue disorder, characterized by short stature, facial dysmorphology, variable intellectual disability, skeletal abnormalities, arthropathy, cardiopathy, laryngotracheal anomalies, and stiff skin. So far, all molecularly confirmed cases harbored a de novo heterozygous gain-of-function mutation in SMAD4, encoding the SMAD4 transducer protein required for both transforming growth factor-beta and bone morphogenic proteins signaling. We report on four novel patients (one female proband and her two affected children, and one male proband) with Myhre syndrome harboring the recurrent c.1486C>T (p.Arg496Cys) mutation in SMAD4. The female proband presented with a congenital heart defect, vertebral anomalies, and facial dysmorphic features. She developed severe tracheal stenosis requiring a total laryngectomy. With assisted reproductive treatment, she gave birth to two affected children. The second proband presented with visual impairment following lensectomy in childhood, short stature, brachydactyly, stiff skin, and decreased peripheral sensitivity. Transmission electron microscopy (TEM) of the dermis shows irregular elastin cores with globular deposits and almost absent surrounding microfibrils and suggests age-related increased collagen deposition. We report on the first familial case of Myhre syndrome and illustrate the variable clinical spectrum of the disorder. Despite the primarily fibrotic nature of the disease, TEM analysis mainly indicates elastic fiber anomalies.
Topics: Adult; Alleles; Amino Acid Substitution; Biopsy; Cryptorchidism; Facies; Female; Genotype; Growth Disorders; Hand Deformities, Congenital; Humans; Intellectual Disability; Male; Middle Aged; Mutation; Phenotype; Radiography; Recurrence; Skin; Smad4 Protein
PubMed: 31595668
DOI: 10.1002/ajmg.a.61377 -
American Journal of Respiratory and... Mar 2020
Topics: Administration, Oral; Adult; Hamartoma Syndrome, Multiple; Humans; Male; Steroids; Tracheal Stenosis; Tracheotomy; Treatment Outcome
PubMed: 31539271
DOI: 10.1164/rccm.201905-0922IM