RESUMEN
Branchio-oto-renal (BOR) syndrome is characterized by ear malformations associated with sensorineural or mixed hearing loss. In addition, preauricular tags, preauricular pits, branchial cleft fistulas and cysts, as well as renal dysplasia are seen. A genetic mutation on chromosome 8, either autosomal dominantly inherited or occuring as a spontaneous mutation, is the cause in the majority of cases. Using array-based comparative genomic hybridization (CGH), it is possible to detect even the smallest genetic changes. Salivary gland choristoma in the middle ear is very rare. Surgical removal and histological clarification are required.
Asunto(s)
Síndrome Branquio Oto Renal/genética , Coristoma/genética , Hibridación Genómica Comparativa/métodos , Enfermedades del Oído/genética , Oído Medio/cirugía , Predisposición Genética a la Enfermedad/genética , Glándulas Salivales/cirugía , Síndrome Branquio Oto Renal/cirugía , Coristoma/cirugía , Enfermedades del Oído/cirugía , Humanos , Lactante , Masculino , Mutación/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. METHODS: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. RESULTS: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. CONCLUSION: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.
Asunto(s)
1-Alquil-2-acetilglicerofosfocolina Esterasa/genética , Corteza Cerebral/anomalías , Predisposición Genética a la Enfermedad/genética , Proteínas Asociadas a Microtúbulos/genética , Mutación/genética , Malformaciones del Sistema Nervioso/genética , Adolescente , Adulto , Movimiento Celular/genética , Cerebelo/anomalías , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Niño , Preescolar , Coristoma/genética , Coristoma/metabolismo , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Lactante , Masculino , Malformaciones del Sistema Nervioso/metabolismo , Malformaciones del Sistema Nervioso/fisiopatología , Penetrancia , FenotipoAsunto(s)
Centrómero/genética , Aberraciones Cromosómicas , Inversión Cromosómica , Cromosomas Humanos Par 3/genética , Discapacidades del Desarrollo/genética , Niño , Preescolar , Bandeo Cromosómico , Discapacidades del Desarrollo/patología , Cara/anomalías , Femenino , Duplicación de Gen , Humanos , Hibridación Fluorescente in SituRESUMEN
We report on four unrelated cases of an Opitz trigonocephaly (C)-like syndrome with a highly characteristic combination of facial anomalies including prominent metopic suture, exophthalmos, hypertelorism, cleft lip and palate, flexion deformities of the upper limbs and multiple other anomalies. We also review two very similar published cases formerly considered to have the C syndrome. Although there is overlap, a clinical distinction from the Opitz trigonocephaly and other syndromes seems possible, and thus a specific causal entity may be postulated.