RESUMO
Giant axonal neuropathy is a severe autosomal recessive neurodegenerative disorder of childhood that affects both the peripheral and central nervous systems. It is caused by mutations in the GAN gene linked to chromosome 16q24.1 At least 45 distinct disease-causing mutations have been identified throughout the gene in families of various ethnic origins, with different symptomatologies and different clinical courses. To date, no characteristic mutation or phenotype-genotype correlation has been established. We describe a novel missense mutation in four siblings born to consanguineous parents of Arab original with clinical and molecular features compatible with giant axonal neuropathy. The phenotype was characterized by a predominant motor and sensory peripheral neuropathies and severe skeletal deformities.
Assuntos
Proteínas do Citoesqueleto/genética , Neuropatia Axonal Gigante/genética , Neuropatia Axonal Gigante/patologia , Anormalidades Musculoesqueléticas/genética , Mutação de Sentido Incorreto/genética , Adolescente , Árabes/genética , Criança , Cromossomos Humanos Par 16/genética , Consanguinidade , Feminino , Humanos , Israel , Anormalidades Musculoesqueléticas/patologia , Linhagem , Irmãos , Nervo Sural/patologiaRESUMO
Velocardiofacial syndrome (VCFS) is characterized by both physical manifestations and neuropsychiatric disabilities. About 6-28% of cases are familial. The aim of the present study was to compare the clinical characteristics of subjects with familial and nonfamilial VCFS, with a special focus on cognitive and psychiatric disabilities. In addition, the complexities of coping with the disease in families in which both a parent and children are affected were highlighted in case vignettes. Sixteen patients from six families with VCFS were compared to 63 subjects with nonfamilial VCFS for physical parameters, IQ, and rate of major psychiatric disorders. After controlling for the effect of age, IQ was significantly lower in the familial compared to the nonfamilial group of VCFS patients. Rate of psychiatric disorders was similarly high in both groups. The familial group had fewer cardiac and palate anomalies. A significant negative correlation was found between IQ and age. Most of the adults with familial VCFS were neuropsychiatrically disabled. Thus, although familial VCFS seems to be associated with a milder physical phenotype than nonfamilial VCFS, the neuropsychiatric deficits are significant in both types, at all ages.
Assuntos
Adaptação Psicológica , Síndrome de DiGeorge/psicologia , Adolescente , Adulto , Doenças Cardiovasculares/congênito , Doenças Cardiovasculares/diagnóstico , Criança , Pré-Escolar , Cognição , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Face/anormalidades , Família , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/etiologia , Heterozigoto , Humanos , Lactente , Testes de Inteligência , Masculino , Casamento , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Palato/anormalidades , PaisRESUMO
The authors describe three siblings born to consanguineous parents with early onset ataxia, dysarthria, myoclonic, generalized tonic clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. Direct screening excluded mutations in FRDA, TDP1,and SACS genes and at 8344, 3243, and 8993 positions of mitochondrial DNA. Linkage analysis excluded AOA-1, EPM1, EPM2A, EPM2B, CAMOS, and recessive ataxias linked to chromosome 9q34-9qter. This clinical constellation may represent a distinct form of early onset cerebellar ataxia.
