RESUMEN
Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, unusual face and breathing abnormalities and can be caused by haploinsufficiency of TCF4. The majority of cases are sporadic. Somatic mosaicism was reported infrequently. We report on a proband with typical manifestations of PTHS and his younger brother with a less striking phenotype. In both, a heterozygous frameshift mutation (c.1901_1909delinsA, p.Ala634AspfsX67) was found in exon 19 of TCF4. The same mutation was found at low levels in DNA extracted from the mother's blood, urine and saliva. This report of familial recurrence with somatic mosaicism in a healthy mother has important consequences for genetic counseling. We suggest careful studies in parents of other patients with PTHS to determine the frequency of germline and somatic mosaicism for TCF4 mutations.
Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Hiperventilación/genética , Discapacidad Intelectual/genética , Mosaicismo , Factores de Transcripción/genética , Adulto , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/sangre , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/orina , Niño , Preescolar , Facies , Femenino , Mutación del Sistema de Lectura , Asesoramiento Genético , Haploinsuficiencia/genética , Humanos , Hiperventilación/sangre , Hiperventilación/diagnóstico , Hiperventilación/orina , Discapacidad Intelectual/sangre , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/orina , Masculino , Madres , Fenotipo , Factor de Transcripción 4 , Factores de Transcripción/sangre , Factores de Transcripción/orinaRESUMEN
BACKGROUND: Increased post-void residual urine volume (PVR) is often seen in geriatric populations. People with intellectual disabilities (ID) have risk factors in common with these populations. AIMS: To investigate in adults with ID: Feasibility of portable ultrasound bladder scanning; Prevalence of PVR; and Relations with proposed risk factors for PVR. METHODS: In a cross-sectional design, PVR was measured using ultrasound scanning in 346 adults with moderate to severe ID aged 18-82 years. Relationship between increased PVR and the following risk factors was assessed: age, level of ID, gender, ambulancy, medication, chronic illnesses, incontinence and profound multiple disabilities (PMD). Acceptation of scanning and manageability were noted. RESULTS: Feasibility: All participants were cooperatively undergoing the ultrasound scan and all outcomes were sufficiently interpretable. Prevalence: PVR >or= 150 mL was newly identified in 30/346 persons (8.7%, 95% confidence interval 5.92-12.14). Associations: Higher age (P = 0.001), laxative use (P = 0.001), chronic illnesses other than epilepsy (P = 0.005), profound ID (P = 0.008), incontinence (P = 0.048) and immobility(P = 0.005) are determinants that were associated with urinary retention. CONCLUSIONS: The bladder ultrasound scan is a feasible method to identify increased PVR in adults with more severe levels of ID. The prevalence of PVR in adults is similar to prevalences found in the geriatric general population.