RESUMEN
Intrachromosomal triplications are rare and can be mistaken for duplications. The majority of triplications reported are de novo, mostly involving chromosome 15q, and have a middle inverted repeat. We report on the clinical, cytogenetic, and molecular analyses of a patient with a novel triplication 13q21.1-q21.33 secondary to a familial duplication 13q21.1-q21.33 with mild phenotypic effect in three generations. The propositus was an 8-year-old boy referred because of language delay and mild mental retardation. His weight, height and OFC were above the 97th centile. He had delayed tooth eruption and subtle dysmorphic features. Chromosome analysis (550 band stage) showed extra material in 13q21. Family history was unremarkable except for adult-onset sensorineural hearing loss in the father and paternal grandfather. Their karyotypes and those of both brothers of the propositus also showed an abnormal chromosome 13 but with less extra genetic material. FISH analysis with several BAC clones showed a triplication in the propositus between 204N9 and 184B18 (which mapped to 13q21.1 and 13q21.33, respectively) and a direct duplication for the same fragment (around 12 Mb) in the rest of the family members with the abnormal chromosome 13. The FISH signals did not show a middle inverted repeat. We describe the first intrachromosomal triplication 13q21.1-q21.33 derived from a paternal duplication. Meiotic instability in the transmission of a duplication has not been previously observed. Phenotypic variability may be explained by chromosomal non-penetrance or dosage critical loci located in the triplicate/duplicate segment.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 13/genética , Anomalías Craneofaciales/genética , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Adolescente , Adulto , Niño , Cromosomas Artificiales Bacterianos , Anomalías Craneofaciales/patología , Femenino , Pérdida Auditiva Sensorineural/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Paternidad , Linaje , Fenotipo , Erupción Dental/genéticaRESUMEN
INTRODUCTION: Hirayama disease is a rare children's muscular atrophy that affects young Asian males, with muscular atrophy usually in one of the upper limbs that progresses slowly and later stabilises. It is diagnosed by means of electromyographic/electroneurographic with conduction speed studies (EMG/ENG-CS) and by magnetic resonance imaging (MRI) of the spinal cord in a neutral position and with cervical flexion. Treatment is based on the cervical collar and surgery (severe cases). Very few studies have been conducted on patients at the paediatric age. CASE REPORT: We report the case of a 7-year-old girl with atrophy of the muscles of the left hand and forearm, and a disease history of two years. The EMG/ENG-CS scans presented signs of very severe chronic denervation in the myotomes of C7, C8 and T1 on the left side, with conservation of the amplitudes of sensory evoked potentials, consistent with cervical myelopathy. Results of an MRI scan of the cervical spinal cord in a neutral position were normal at that level. Later, owing to suspicions pointing towards Hirayama disease, a new MRI scan of the cervical spinal cord was performed in a neutral position and in flexion. This second scan showed asymmetry in the size and morphology of the anterior funiculi of the spinal cord at C6/C7, hypersignal in the homolateral anterior horn and ingurgitation of the posterior epidural venous plexus. With a diagnosis of Hirayama disease, treatment is started with a cervical collar in order to prevent the damage from getting worse. CONCLUSIONS: This case of Hirayama disease is peculiar due to its epidemiological characteristics and is presented here with the aim of making this entity more widely known in our milieu. If diagnosed at an early stage, treatment is effective, and the studies conducted on children at the paediatric age are reviewed.
TITLE: Enfermedad de Hirayama en pediatria: aportacion de un caso clinico y revision de la bibliografia.Introduccion. La enfermedad de Hirayama es una rara atrofia muscular juvenil que afecta a varones jovenes de origen asiatico, con atrofia muscular habitualmente de una de las extremidades superiores de progresion lenta con estabilizacion posterior. Se diagnostica por estudios electromiograficos/electroneurograficos con velocidad de conduccion (EMG/ENG-VC), y por resonancia magnetica (RM) medular en posicion neutra y en flexion cervical. El tratamiento se basa en el collarin cervical y cirugia (casos graves). Son muy pocos los estudios realizados en edad pediatrica. Caso clinico. Niña de 7 años, con atrofia de la musculatura de la mano y el antebrazo izquierdos, de dos años de evolucion. En EMG/ENG-VC presenta signos de denervacion cronica muy grave en los miotomos correspondientes a C7, C8 y D1 izquierdos, con conservacion de amplitudes de potenciales sensitivos evocados, congruentes con mielopatia cervical. La RM medular cervical en posicion neutra muestra un resultado normal en ese nivel. Posteriormente, por la sospecha dirigida de enfermedad de Hirayama, se realiza una nueva RM medular cervical en posicion neutra y en flexion, que muestra asimetria en el tamaño y morfologia de los cordones anteriores medulares en C6/C7, hiperseñal en el asta anterior homolateral e ingurgitacion del plexo venoso epidural posterior. Con el diagnostico de enfermedad de Hirayama se inicia tratamiento con collarin cervical para evitar la progresion del daño. Conclusiones. Se presenta un caso de enfermedad de Hirayama peculiar por las caracteristicas epidemiologicas, con la finalidad de difundir esta entidad en nuestro medio, cuyo diagnostico precoz permite un tratamiento eficaz, y se revisan los estudios realizados en edad pediatrica.