RESUMO
OBJECTIVE: We conducted a pilot screening program to define the prevalence of non-syndromic deafness and establish the frequency of mutations in the GJB2 gene (Cx26) in a population of children with congenital deafness in Bogotá, Colombia. METHOD: From a cohort of 731 children in 8 institutions for the deaf, we identified 322 (44%) with presumed non-syndromic deafness. These were invited to a more detailed evaluation, but 46 chose not to participate. The remaining 276 individuals received a complete ophthalmological evaluation that was normal in 205 (74.3%) and showed salt and pepper retinopathy in 55 (19.9%) and other ocular abnormalities in 16 (5.8%). A comprehensive medical history, and a detailed physical examination were performed in the 205 children with normal ocular exam. Of these, 93 were found to have acquired deafness and/or associated anomalies and 112 (15.3% of the initial 731 children), non-syndromic deafness. The GJB2 gene was sequenced in these 112 individuals. RESULTS: Based on family history, 59.8% (67/112) of these cases had autosomal recessive non-syndromic sensorineural hearing loss and the remaining 40.2% (45/112) were sporadic, without apparent known cause. We identified three mutations in the GJB2 gene: 35delG, S199F, and 167delT, all of which have been previously reported in the literature, the variant M34T, and the polymorphism V27I. S199F was the most frequent mutation (17.9%), followed by 35delG (17.0%) and 167delT (0.4%). The mutations in the GJB2 gene were present in 50.7% of the autosomal recessive group and in 33.3% of the sporadic cases. CONCLUSIONS: Our pilot study showed that 15.3% of institutionalized deaf children in Bogotá have non-syndromic deafness and among them, the frequency of the S199F mutation was higher than reported in previous studies, whereas the frequency of the 35delG is similar to Caucasian populations. The fact that the S199F mutation was the most frequent allele in our study confirms the fact that the prevalence of GJB2 mutations depends on the ethnic origin. We emphasize the need to follow a strict protocol to identify bona fide cases of non-syndromic deafness among individuals with congenital hearing loss in order to identify the molecular basis of this condition.
Assuntos
Conexinas/genética , Surdez/epidemiologia , Surdez/genética , Testes Genéticos , Mutação/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Colômbia , Conexina 26 , Surdez/congênito , Humanos , Projetos Piloto , Prevalência , Avaliação de Programas e Projetos de SaúdeRESUMO
We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients and abnormal coordination in 33.4% of US1, and in 58.3% of US2. Borderline mental retardation, depression or bipolar affective disorder were observed in 16.7% of US1 and 33.3% of US2 patients. MRI analysis showed cerebellar abnormalities in 50% of US1 and 75% of US2 patients, but no clear correlation was observed between structural abnormalities and clinical findings. A pattern for the MRI classification of US patients is suggested.
Assuntos
Anormalidades Múltiplas/fisiopatologia , Encéfalo/anormalidades , Perda Auditiva Neurossensorial/fisiopatologia , Retinose Pigmentar/fisiopatologia , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Linhagem , Retinose Pigmentar/patologiaRESUMO
Facial morphometry using computerised image analysis was performed on patients with growth hormone receptor deficiency (Laron syndrome) from an inbred population of southern Ecuador. Morphometrics were compared for 49 patients, 70 unaffected relatives, and 14 unrelated persons. Patients with growth hormone receptor deficiency showed significant decreases in measures of vertical facial growth as compared to unaffected relatives and unrelated persons with short stature from other causes. This report validates and quantifies the clinical impression of foreshortened facies in growth hormone receptor deficiency.
Assuntos
Antropometria , Nanismo/patologia , Face/patologia , Receptores da Somatotropina/deficiência , Adolescente , Adulto , Idoso , Estatura , Cefalometria , Criança , Consanguinidade , Nanismo/etnologia , Nanismo/genética , Equador , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Judeus/genética , Masculino , Pessoa de Meia-Idade , Fotografação , Receptores da Somatotropina/genética , Espanha/etnologia , SíndromeRESUMO
To identify causative factors we screened 1,715 deaf individuals from 16 schools for the deaf in Colombia. We found evidence of environmental causation in 579 (33.8%) cases, genetic in 608 (35.4%), and in 528 (30.8%) we were unable to identify the etiology. The degree of hearing loss was severe to profound in 1,238 (72.2%), although in 987 (57.5%) of the deaf population studied the hearing impairment was not noticed until 2 to 5 years of age. The frequent association of deafness with other anomalies underscores the importance of a careful clinical and ophthalmologic evaluation in individuals with hearing loss. Our observations also emphasize the need for programs directed towards the prevention of hearing loss, including primary prevention as well as early diagnosis, investigation of possible genetic causes, and rehabilitation of deaf individuals.
Assuntos
Surdez/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Colômbia , Humanos , InstitucionalizaçãoRESUMO
Otological, ophthalmological and genetic studies were performed in 46 patients with Usher syndrome, identified through a screening program in Colombia. Of them, 69.6% had Usher syndrome type I, 26.1% type II, and 4.3% type III. Thirty-three patients showed profound deafness (71.7%), while 13 (28.3%) had moderate to severe hearing loss. The ophthalmologic manifestations showed marked variability. Although the majority of the patients had serious ocular impairment before age 20, 32.6% had good central visual acuity. The prevalence of Usher syndrome in Colombia, estimated at 3.2/100,000, warrants the implementation of screening programs in schools for the deaf and for the blind. Our study confirms that Usher syndrome shows no geographic or racial variation and that the disorder has a wide variability of expression and genetic heterogeneity. The large size of the families we have detected may provide important opportunities for further genetic studies, particularly in terms of the assignment of the locus and gene mapping.
Assuntos
Perda Auditiva Neurossensorial/genética , Programas de Rastreamento/métodos , Retinose Pigmentar/genética , Colômbia/epidemiologia , Consanguinidade , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Humanos , Masculino , Linhagem , Prevalência , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/epidemiologia , SíndromeRESUMO
Analysis of cephalometric radiographs of 12 children with fetal alcohol syndrome corroborated the clinical observation of midfacial deficiency described in patients with this disorder. Contrary to previous reports, however, our data show that this abnormality is not caused by true maxillary hypoplasia but by retrusion of the maxilla. We postulate that this abnormal position is secondary to restricted forward growth of the face, resulting from abnormal brain growth and subsequent shortening of the anterior cranial base.