RESUMEN
Chromosome 22q11.2 deletion syndrome is common and presents with a range of clinical features from cardiac malformations to hypocalcemia. Laryngeal anomalies are not a common feature of this syndrome. We describe newly born twins who presented with unexpected severe birth depression secondary to severe type IV glottic webs requiring extensive resuscitation and emergency tracheostomy. They were diagnosed postnatally to have deletion of 22q11.2. The successful resuscitation of these infants at birth was only possible because they were born in a tertiary care hospital. This report shows the critical nature of prenatal diagnosis of 22q11.2 deletion syndrome.
Asunto(s)
Síndrome de Deleción 22q11/diagnóstico , Enfermedades en Gemelos/diagnóstico , Hipotermia Inducida/métodos , Laringoestenosis/diagnóstico , Traqueostomía/métodos , Síndrome de Deleción 22q11/complicaciones , Síndrome de Deleción 22q11/terapia , Adulto , Enfermedades en Gemelos/complicaciones , Enfermedades en Gemelos/genética , Enfermedades en Gemelos/terapia , Padre , Femenino , Humanos , Recién Nacido , Laringoscopía , Laringoestenosis/complicaciones , Laringoestenosis/genética , Laringoestenosis/terapia , Embarazo , Embarazo Gemelar , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , GemelosRESUMEN
An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.