Unmet clinical needs and burden in Angelman syndrome: a review of the literature

Abstract

BackgroundAngelman syndrome (AS) is a rare disorder with a relatively well-defined phenotype. Despite this, very little is known regarding the unmet clinical needs and burden of this condition, especially with regard to some of the most prevalent clinical features—movement disorders, communication impairments, behavior, and sleep.Main textA targeted literature review using electronic medical databases (e.g., PubMed) was conducted to identify recent studies focused on specific areas of the AS phenotype (motor, communication, behavior, sleep) as well as epidemiology, diagnostic processes, treatment, and burden. 142 articles were reviewed and summarized. Findings suggest significant impairment across the life span in all areas of function. While some issues may resolve as individuals get older (e.g., hyperactivity), others become worse (e.g., movement disorders, aggression, anxiety). There are no treatments focused on the underlying etiology, and the symptom-based therapies currently prescribed do not have much, if any, empirical support.ConclusionsThe lack of standardized treatment protocols or approved therapies, combined with the severity of the condition, results in high unmet clinical needs in the areas of motor functioning, communication, behavior, and sleep for individuals with AS and their families.

Anxiety‐associated and separation distress‐associated behaviours in Angelman syndrome

“…Sleep difficulties, seizures and other medical and behavioural features are also frequently present (see Wheeler et al . for a review).…”

“…Included in the consistent features are functionally severe developmental delays, little to no use of speech, movement disorders and a unique behavioural profile that includes frequent laughing, smiling and excitability as well as hyperactivity. Sleep difficulties, seizures and other medical and behavioural features are also frequently present (see Wheeler et al 2017 for a review).…”

Historias de vida de familias con hijos e hijas con síndrome de Angelman

“…El síndrome de Angelman como enfermedad rara que afecta a las familias E l síndrome de Angelman (SA) fue descrito por primera vez por el doctor Harry Angelman en 1965 (Artigas, Brun, Gabau, Guitart y Camprubí, 2005;Napier, Tones, Simons, Heussler, Hunter, Cross y Bellgard, 2017. Se trata de un trastorno raro con un fenotipo relativamente bien definido (Wheeler, Sacco y Cabo, 2017), ya que es un trastorno del neurodesarrollo poco frecuente causado por la pérdida de la función UBE3A, un gen impreso y expresado en el cromosoma 15 (Napier et al, 2017;Wheeler et al, 2017;Wulffaert, Scholte y van Berckelaer-Onnes, 2010). Según Wheeler et al (2017), existen 4 tipologías conocidas del SA responsables del gen UBE3A: deleción en el cromosoma 15q11-q13 (en el 70% de los casos); disomía uniparental paterna (UPD, en el 2% de los casos); defecto de impresión (en el 3% de los casos); y mutación puntual (en el 10% de los casos).…”

“…La prevalencia del SA se estima generalmente, aproximadamente en uno de cada 15000 nacimientos, aunque la verdadera prevalencia no está bien caracterizada (Wheeler et al, 2017). Según Napier et al (2017), la prevalencia estimada es de 1 entre 15000-24000 y cabe destacar que actualmente no existe cura.…”

“…Dicho trastorno se caracteriza por una discapacidad grave del desarrollo, pérdida del habla, dificultades en el control y planificación motriz, dificultades significativas del sueño, riesgo elevado de convulsiones y características únicas de conducta (Hong et al 2017;Wheeler et al, 2017). Napier et al (2017) también añaden la epilepsia y una disposición de felicidad.…”