RESUMEN
PURPOSE: Describe the clinical and molecular findings of patients with Kabuki syndrome (KS) who present with hypoglycemia due to congenital hyperinsulinism (HI), and assess the incidence of KS in patients with HI. METHODS: We documented the clinical features and molecular diagnoses of 9 infants with persistent HI and KS via a combination of sequencing and copy-number profiling methodologies. Subsequently, we retrospectively evaluated 100 infants with HI lacking a genetic diagnosis, for causative variants in KS genes. RESULTS: Molecular diagnoses of KS were established by identification of pathogenic variants in KMT2D (n = 5) and KDM6A (n = 4). Among the 100 infants with HI of unknown genetic etiology, a KS diagnosis was uncovered in one patient. CONCLUSIONS: The incidence of HI among patients with KS may be higher than previously reported, and KS may account for as much as 1% of patients diagnosed with HI. As the recognition of dysmorphic features associated with KS is challenging in the neonatal period, we propose KS should be considered in the differential diagnosis of HI. Since HI in patients with KS is well managed medically, a timely recognition of hyperinsulinemic episodes will improve outcomes, and prevent aggravation of the preexisting mild to moderate intellectual disability in KS.
Asunto(s)
Anomalías Múltiples/genética , Hiperinsulinismo Congénito/genética , Proteínas de Unión al ADN/genética , Cara/anomalías , Enfermedades Hematológicas/genética , Histona Demetilasas/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Enfermedades Vestibulares/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/fisiopatología , Preescolar , Hiperinsulinismo Congénito/complicaciones , Hiperinsulinismo Congénito/diagnóstico , Hiperinsulinismo Congénito/fisiopatología , Cara/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/fisiopatología , Humanos , Lactante , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/fisiopatología , Masculino , Mutación , Patología Molecular , Estudios Retrospectivos , Enfermedades Vestibulares/complicaciones , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/fisiopatologíaRESUMEN
The author Diva D. De Leon was incorrectly listed as instead of Diva D. De Leó-Critchlow in the original version of this paper.