RESUMO
Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.
Assuntos
Fenótipo , Proteína Smad4 , Humanos , Feminino , Masculino , Criança , Adolescente , Proteína Smad4/genética , Pré-Escolar , Adulto , Lactente , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Criptorquidismo/genética , Criptorquidismo/patologia , Massachusetts/epidemiologia , Adulto Jovem , Fácies , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Transtornos do Crescimento/epidemiologia , Genótipo , Hospitais Gerais , Pé Torto Equinovaro/genética , Pé Torto Equinovaro/patologia , Pé Torto Equinovaro/epidemiologia , Mutação/genética , Deformidades Congênitas da MãoRESUMO
Given the increasing use of MRI in the pediatric population, the need for sedation in MRI performed in young children is a topic of growing importance. Although sedation is generally tolerated well by children, the financial and operational impacts of anesthesia on MRI workflow, as well as potential adverse effects of anesthetic medications, highlight the need to perform MRI in children without sedation whenever possible. This review focuses on current techniques to facilitate non-sedation MRI in children, including exam preparation with MRI simulation; asleep but not sedated techniques; awake and relaxed techniques using certified child life specialists, animal-assisted therapy, a child-friendly environment and in-scan entertainment; and non-sedated MRI protocol modifications such as shorter scan time, prioritizing sequences, reducing motion artifact, noise reduction, limiting use of gadolinium, employing an open MRI and modifying protocols.