Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. DISCUSSION: Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

[Reliability for detection of developmental problems using the semaphore from the Child Development Evaluation test: Is a yellow result different from a red result?] / Confiabilidad de la detección de problemas de desarrollo mediante el semáforo de la prueba de Evaluación del Desarrollo Infantil: ¿es diferente un resultado amarillo de uno rojo?

BACKGROUND: The Child Development Evaluation (CDE) is a screening tool designed and validated in Mexico for detecting developmental problems. The result is expressed through a semaphore. In the CDE test, both yellow and red results are considered positive, although a different intervention is proposed for each. The aim of this work was to evaluate the reliability of the CDE test to discriminate between children with yellow/red result based on the developmental domain quotient (DDQ) obtained through the Battelle Development Inventory, 2nd edition (in Spanish) (BDI-2). METHODS: The information was obtained for the study from the validation. Children with a normal (green) result in the CDE were excluded. Two different cut-off points of the DDQ were used (BDI-2): <90 to include low average, and developmental delay was considered with a cut-off<80 per domain. Results were analyzed based on the correlation of the CDE test and each domain from the BDI-2 and by subgroups of age. RESULTS: With a cut-off DDQ<90, 86.8% of tests with yellow result (CDE) indicated at least one domain affected and 50% 3 or more compared with 93.8% and 78.8% for red result, respectively. There were differences in every domain (P<0.001) for the percent of children with DDQ<80 between yellow and red result (CDE): cognitive 36.1% vs. 61.9%; communication: 27.8% vs. 50.4%, motor: 18.1% vs. 39.9%; personal-social: 20.1% vs. 28.9%; and adaptive: 6.9% vs. 20.4%. CONCLUSIONS: The semaphore result yellow/red allows identifying different magnitudes of delay in developmental domains or subdomains, supporting the recommendation of different interventions for each one.

Confiabilidad de la detección de problemas de desarrollo mediante el semáforo de la prueba de Evaluación del Desarrollo Infantil: ¿es diferente un resultado amarillo de uno rojo? / Reliability for detection of developmental problems using the semaphore from the Child Development Evaluation test: Is a yellow result different from a red result?

Introducción: La prueba Evaluación del Desarrollo Infantil (EDI) es un instrumento de tamizaje de problemas en el desarrollo diseñado y validado en México. La calificación obtenida se expresa como semáforo. Se consideran positivos tanto el resultado amarillo como el rojo, aunque se plantea una intervención diferente para cada uno. El objetivo de este trabajo fue evaluar la capacidad de la prueba EDI para discriminar entre los niños identificados con semáforo amarillo y los identificados con rojo al compararse con el Inventario de Desarrollo de Battelle 2.ª edición (IDB-2) en cuanto al cociente de desarrollo del dominio (CDD). Métodos: El análisis se llevó a cabo utilizando la información obtenida para el estudio de la validación. Se excluyeron los pacientes con resultado normal (verde) en EDI. Se utilizaron 2 puntos de CDD (IDB-2) por dominio: < 90 para incluir normal-bajo y < 80 para diagnóstico de retraso. Se analizó el resultado con base en la correlación del resultado del semáforo de EDI (amarillo o rojo) y el IDB-2, total y por subgrupos de edad. Resultados: Al considerar un CDD < 90 en amarillo, el 86.8% tuvo al menos un dominio afectado, y el 50%, 3 o más dominios, en comparación con el 93.8% y el 78.8% para el resultado en rojo, respectivamente. Hubo diferencias en todos los dominios entre amarillos y rojos (p < 0.001) para el porcentaje de niños con un CDD < 80: cognitivo (36.1 vs. 61.9%); comunicación (27.8 vs. 50.4%); motor (18.1 vs. 39.9%); personal-social (20.1 vs. 28.9%); y adaptativo (6.9 vs. 20.4%). Conclusiones: Los resultados de semáforo (amarillo o rojo) permiten identificar diferente magnitud de los problemas en el desarrollo y apoyan intervenciones diferenciadas.

Background: The Child Development Evaluation (CDE) is a screening tool designed and validated in Mexico for detecting developmental problems. The result is expressed through a semaphore. In the CDE test, both yellow and red results are considered positive, although a different intervention is proposed for each. The aim of this work was to evaluate the reliability of the CDE test to discriminate between children with yellow/red result based on the developmental domain quotient (DDQ) obtained through the Battelle Development Inventory, 2nd edition (in Spanish) (BDI-2). Methods: The information was obtained for the study from the validation. Children with a normal (green) result in the CDE were excluded. Two different cut-off points of the DDQ were used (BDI-2): < 90 to include low average, and developmental delay was considered with a cut-off < 80 per domain. Results were analyzed based on the correlation of the CDE test and each domain from the BDI-2 and by subgroups of age. Results: With a cut-off DDQ <90, 86.8% of tests with yellow result (CDE) indicated at least one domain affected and 50% 3 or more compared with 93.8% and 78.8% for red result, respectively. There were differences in every domain (P < 0.001) for the percent of children with DDQ < 80 between yellow and red result (CDE): cognitive 36.1% vs. 61.9%; communication: 27.8% vs. 50.4%, motor: 18.1% vs. 39.9%; personal-social: 20.1% vs. 28.9%; and adaptive: 6.9% vs. 20.4%. Conclusions: The semaphore result yellow/red allows identifying different magnitudes of delay in developmental domains or subdomains, supporting the recommendation of different interventions for each one.

Validación de un instrumento para la detección oportuna de problemas de desarrollo en menores de 5 años en México / Validation of an instrument for early detection of developmental problems in children under 5 years in Mexico

Introducción. En México, no se contaba con una prueba de evaluación del desarrollo infantil con propiedades psicométricas. La prueba de evaluación del desarrollo infantil (EDI) se desarrolló con este fin. El objetivo de este trabajo fue determinar las propiedades psicométricas de la EDI como prueba de tamizaje para los problemas de desarrollo infantil en menores de 5 años. Métodos. Se realizó un estudio transversal que incluyó pacientes menores de 5 años en tres entidades de la República Mexicana: Chihuahua, Yucatán y Distrito Federal. El espectro de la población incluyó niños con factores de riesgo biológico, ambiental y sin riesgo para retraso en el desarrollo. Se excluyeron los pacientes con alteraciones neurológicas evidentes. Se consideró, como prueba diagnóstica, el Inventario de Desarrollo de Battelle-2 en las tres entidades. En el Distrito Federal, adicionalmente, se aplicó Bayley-III. A cada participante se le aplicaron la prueba de tamizaje en dos versiones y la prueba diagnóstica, el mismo día o en un lapso no mayor a una semana. La persona que aplicó la prueba diagnóstica no conocía el resultado de la prueba de tamizaje. Se definió retraso cuando el cociente total de desarrollo resultó menor a 90. Resultados. Se incluyeron, en total, 438 niños menores de 5 años provenientes del Distrito Federal (n =152, 34.7%), Yucatán (n =151, 34.5%) y Chihuahua (n =135, 30.8%). Del total, 43.4% fueron del sexo femenino (n =190). La clasificación por tipo de riesgo fue biológico (n =197, 45%), ambiental (n =137, 31.3%) y sin riesgo (n =104, 23.7%). Se encontró una sensibilidad de 0.81 (IC 95%: 0.75-0.86), especificidad de 0.61 (IC 95%: 0.54-0.67), concordancia 0.70 (IC 95%: 0.66-0.74). La correlación parcial de las áreas del desarrollo entre la prueba de tamizaje y la prueba Bayley III (n =87) ajustada por grupo de edad del tamizaje fue la siguiente: área motor fino 0.468, motor grueso 0.441, lenguaje 0.508, social 0.336 y adaptativo 0.355 (p ≤0.001). Conclusiones. La prueba EDI posee propiedades adecuadas y similares a las pruebas más utilizadas en América.

Background. The ''Evaluación del Desarrollo Infantil'' (EDI) test was developed as an screening tool for the developmental evaluation of Mexican children younger than 5 years old. The objective of this study was to evaluate the psychometric properties of EDI as a screening tool for children with developmental problems. Methods. We carried out a cross-sectional study including patients from urban and rural areas in three locations: Mexico City, Yucatan and Chihuahua. The disease spectrum was defined according to biological risk, environmental risk or without risk for developmental problems. Patients with obvious neurological disabilities or genetic syndromes were excluded. The gold standards were the Battelle Developmental Inventory 2 (in Spanish) and Bayley-III. Each participant had two complete applications of the EDI test (all interrogated and all observed) and the gold standard (Bayley-III only in Mexico City). Developmental delay was defined as a total development quotient <90. Results. The study included 438 children <5 years old. Distribution by site includes Mexico City (n =152, 34.7%), Yucatan (n =151, 34.5%), Chihuahua (n =135, 30.8%); female gender (n =190, 43.4%). Classification by risk includes biological (n =197, 45%), environmental (n =137, 31.3%), without risk (n =104, 23.7%). With BDI-II as the gold standard, the modified version of EDI (interrogated plus observation) has a sensitivity of 0.81 (95% CI: 0.75-0.86), specificity 0.61 (95% CI: 0.54-0.67), and concordance 0.70 (95% CI: 0.66-0.74). The partial correlation between EDI areas and Bayley-III areas (n =87) was adjusted by test group: fine motor 0.468, gross motor 0.441, language 0.508, social 0.336 and adaptive 0.355 (p ≤0.001). Conclusions. The modified version of EDI has similar properties as the various developmental screening tools available in the U.S. or Latin America and could be a good screening tool in Spanish.

Pruebas de tamizaje de neurodesarrollo global para niños menores de 5 años de edad validadas en Estados Unidos y Latinoamérica: revisión sistemática y análisis comparativo / Global neurodevelopmental screening tests for children under 5 years of age in the United States and Latin America: systematic review and comparative analysis

Introducción. La Academia Americana de Pediatría recomienda aplicar, sistemáticamente, pruebas de tamizaje del neurodesarrollo para el oportuno diagnóstico y tratamiento. Para lograr referir apropiadamente a los pacientes, es importante tener información bien fundamentada sobre estas herramientas. Métodos. Se realizó una revisión sistemática de estudios de validación de pruebas de tamizaje de neurodesarrollo para menores de 5 años en Estados Unidos y Latinoamérica, de 1980 a 2012. Resultados. Se encontraron 13 pruebas con diferentes características de evaluación y calificación. Obtuvieron la mejor sensibilidad y especificidad Battelle Developmental Inventory Screening (2nd Edition) (0.93 y 0.88) y PRUNAPE con VPP 0.94 y VPN 0.97. Conclusiones. De 1980 a 2012, se encontraron 13 pruebas de tamizaje del neurodesarrollo para menores de 5 años en Estados Unidos y Latinoamérica. La Battelle Developmental Inventory Screening obtuvo la mayor validez de criterio, y la PRUNAPE fue la más predictiva. No se encontraron estudios de validación en México. Por lo tanto, se consideró de vital importancia contar con una herramienta validada en nuestro país.

Background. The American Academy of Pediatrics recommends the application of neurodevelopmental screening tests for early intervention of neurodevelopmental disorders. In order to refer these tests appropriately, it is important to have well-founded information in regard to these tools. Methods. A systematic literature search targeted on validation studies of neurodevelopmental screening tests in children <5 years of age in the U.S. and Latin America from 1980 to 2012 was conducted. Results. We found 19 validation studies of 13 screening tests. Battelle Developmental Screening Inventory (2nd edition) reported the best sensitivity and specificity (0.93/0.88) and PRUNAPE with predictive positive and negative values (0.94/0.97). Conclusions. From 1980-2012we found 13 neurodevelopmental screening tests in the U.S. and Latin America for children <5 years of age. The best criterion and predictive validity was for Battelle Developmental Inventory Screening and PRUNAPE, respectively. No validation studies were found in Mexico; therefore, we consider it important to have a validated tool in our country.