RESUMO
A 9-yr 8-mo-old right-handed female presented with a history of gait difficulties, which first became apparent at age 9 mo of age, along with slurred speech and hand tremors while holding a tray. Her past medical history was significant for global developmental delay, and she was attending fourth grade special education classes. On examination, she had an ataxic gait, dysarthria, absent deep tendon reflexes, and flexor plantar responses. There were no signs of optic atrophy or hearing loss. Nerve conduction studies were consistent with an axonal neuropathy. A fascicular sural nerve biopsy showed a marked decrease of myelinated fibers larger than 6 µm in diameter as compared with an age-matched control. By electron microscopy, clusters of degenerating axonal mitochondria in both myelinated and unmyelinated fibers were frequently found. Whole-exome sequencing revealed a heterozygous c.314C > T (p.Thr105Met) missense variant in MFN2 in the patient but not in her mother. The father was unavailable for testing. The phenotypes with MFN2 variants can be quite variable, including intellectual disability, optic atrophy, auditory impairment, spinal atrophy with or without hydromyelia, and hydrocephalus. We report here that early onset ataxia with intellectual disability can also be associated with MFN2-related Charcot-Marie-Tooth, Type 2A2A diagnosis, the most common type of autosomal dominant axonal neuropathy.
Assuntos
Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Fenótipo , Degenerações Espinocerebelares/diagnóstico , Degenerações Espinocerebelares/genética , Idade de Início , Axônios/ultraestrutura , Biomarcadores , Mapeamento Cromossômico , Família , Feminino , GTP Fosfo-Hidrolases/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Humanos , Lactente , Mitocôndrias/genética , Mitocôndrias/ultraestrutura , Proteínas Mitocondriais/genética , Mutação , Gravidez , Avaliação de Sintomas , Sequenciamento do ExomaRESUMO
A 12 year-old girl presented with cognitive disability and dysmorphic features. Chromosome microarray analysis revealed a de novo, approximately 4.5 Mb terminal deletion of the short arm of chromosome 12 at 12p13.33 region: chr12:100712-4607067. At 13 years this patient developed psychotic manifestations and was admitted to a psychiatric department for treatment. She started hearing voices, talking to herself and laughing without reason. We have previously reported a male individual with psychotic manifestations and a larger (6.2 Mb) terminal deletion in the same chromosomal region. The present case along with previous reports, define a 2 Mb region on chromosome 12p, where a psychosis-associated gene may be located. Included in this psychosis-associated area are 18 OMIM listed genes.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 12/genética , Transtornos Psicóticos/genética , Anormalidades Múltiplas/genética , Criança , Transtornos Cognitivos/genética , Feminino , Loci Gênicos , HumanosRESUMO
BACKGROUND: Self-injurious behavior (SIB) is one of the most common challenging behaviors in persons with autistic disorder or severe/profound mental retardation. Many psychotropic drugs have been evaluated for their effectiveness in SIB. Results have varied, and no one psychotropic drug has been indicated for SIB. In this prospective, open clinical study, psychotropic drugs were used to treat the previously undiagnosed psychiatric disorder in persons exhibiting SIB. METHOD: Data were collected from 26 individuals with mental retardation (14 males, 12 females), 7 to 45 years of age (mean = 30.3 years), who exhibited SIB. Psychiatric diagnosis was made according to DSM-III-R and DSM-IV criteria. The Behavior Problem Inventory, Yudofsky's Overt Aggression Scale, repeated direct observation, and information on use of protective devices and Likert scales from log books were used to evaluate degree of SIB. Most of the patients were treated with different psychotropic drugs and behavior modification before they were evaluated for this study, but only 7 of them carried a psychiatric diagnosis. Data were collected between 1987 and 1997. RESULTS: Depressive disorders, impulse-control disorder, and anxiety disorder were the most common final diagnoses. Neuroleptics were discontinued in 5 patients and tapered by 50% to 75% in 14 patients. Antidepressants were added in 12 patients. Treatment of psychiatric disorders produced significant (p < .001) decrease in the severity of SIB in the 26 patients, and SIB was eliminated in 12 patients. The severity of SIB decreased to mild from a moderate, severe, or extreme degree in 11 patients and from an extreme to a severe degree in 3 patients. CONCLUSION: The most effective treatment for SIB that is resistant to environment changes and behavior modification in persons with developmental disabilities is the treatment of their psychiatric disorders with the appropriate psychotropics.
