Anomalías cromosómicas subteloméricas en pacientes con retraso mental criptogénico / Subtelomeric rearrangements in cryptogenic mental retardation

Introducción: El retraso mental afecta al 3% de la población. En el 50% no es posible determinar la etiología. Las alteraciones cromosómicas submicroscópicas subteloméricas, no detectables con técnicas citogenéticas convencionales, pueden explicar algunos casos de retraso mental criptogénicos. Pacientes y métodos: Cohorte de 200 pacientes, con edades comprendidas entre los 2,5 y los 15 años, y retraso psicomotor (< 6 años) o retraso mental (> 6 años) criptogénicos. Variables: grado de retraso, dismorfias (faciales, manuales, macrosomía/microsomía), crecimiento intrauterino retardado, epilepsia. Identificación de reordenamientos cromosómicos subteloméricos mediante MLPA (multiplex ligation dependent probe amplification), que detecta pérdidas o ganancias de material genético. Confirmación de los hallazgos patológicos mediante FISH (fluorescent in situ hybridization) y/o array de CGH (comparative genomic hybridization). Resultados: Se detectaron anomalías subteloméricas en 9 pacientes, lo que representa el 4,5% de los casos. El estudio de progenitores demostró en un caso una traslocación en equilibrio. El resto eran alteraciones «de novo». Existía asociación significativa con la presencia de más de un rasgo fenotípico dismórfico o el antecedente de crecimiento intrauterino retardado, pero no con el grado de retraso ni con la presencia de epilepsia. Conclusiones: Las alteraciones cromósomicas submicroscópicas subteloméricas explican el 4,5% de los retrasos mentales de causa desconocida en nuestra serie. En nuestra población se asocian a la presencia de más de un rasgo fenotípico anormal o al antecedente de crecimiento intrauterino retardado (AU)

Introduction: Mental retardation affects 3% of the population, the origin of which cannot be established in 50% of cases. Subtelomeric rearrangements, not detected by routine cytogenetic studies, might explain some cases of unknown cause. Patients and methods: A study was conducted on 200 subjects with unexplained mental retardations using multiplex ligation dependent probe amplification (MLPA). Abnormal findings were confirmed by fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization technology (CGH-array). Results: A subtelomeric aberration was identified in 9 patients. Eight were «de novo»; one was inherited from a phenotypically normal parent. There was a statistically significant association with the presence of more than one dysmorphic feature or with intrauterine growth retardation, but not with the severity of retardation or epilepsy. Conclusions: Subtelomeric rearrangements explained 4.5% of cases of mental retardation in our series. The presence of more than one dysmorphic feature or intrauterine uterine growth retardation increases the probability of this type of chromosomal aberration (AU)

[Subtelomeric rearrangements in cryptogenic mental retardation]. / Anomalías cromosómicas subteloméricas en pacientes con retraso mental criptogénico.

INTRODUCTION: Mental retardation affects 3% of the population, the origin of which cannot be established in 50% of cases. Subtelomeric rearrangements, not detected by routine cytogenetic studies, might explain some cases of unknown cause. PATIENTS AND METHODS: A study was conducted on 200 subjects with unexplained mental retardations using multiplex ligation dependent probe amplification (MLPA). Abnormal findings were confirmed by fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization technology (CGH-array). RESULTS: A subtelomeric aberration was identified in 9 patients. Eight were «de novo¼; one was inherited from a phenotypically normal parent. There was a statistically significant association with the presence of more than one dysmorphic feature or with intrauterine growth retardation, but not with the severity of retardation or epilepsy. CONCLUSIONS: Subtelomeric rearrangements explained 4.5% of cases of mental retardation in our series. The presence of more than one dysmorphic feature or intrauterine uterine growth retardation increases the probability of this type of chromosomal aberration.