Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin-1 gene.
ABSTRACT Oligophrenin-1 (OPHN-1) gene disruption is known as responsible for so called "non-specific" X-linked mental retardation (MR) Billuart et al. [1998: Nature 392:923-926]. In order to search for a possible specific clinical and radiological profile for mutation in the OPHN-1 gene, clinical and 3D brain MRI studies were performed in the two families with a known mutation in OPHN-1 reported so far: a 19-year-old female with an X;12 balanced translocation encompassing OPHN-1, and four affected males of family MRX60 sharing a frameshift mutation in OPHN-1. Clinical data shared by affected individuals were neonatal hypotonia with motor delay but no obvious ataxia, marked strabismus, early onset complex partial seizures, and moderate to severe MR. Brain MRIs performed in three individuals exhibited a specific vermian dysgenesis including an incomplete sulcation of anterior and posterior vermis with the most prominent defect in lobules VI and VII. In addition, a non-specific cerebral cortico-subcortical atrophy was also observed. These clinical and radiological features suggest a distinct clinico-radiological syndrome. These preliminary data need to be confirmed in other families and will be helpful for further targeted mutation screening of the OPHN-1 gene in male patients with similar clinico-radiological features. In addition, OPHN-1 inactivation should be considered as a relevant model of developmental vermis disorganization, leading to a better understanding of the possible role of the cerebellum in MR.
- SourceAvailable from: Giovambattista De Sarro[show abstract] [hide abstract]
ABSTRACT: One hundred and ninety-two fragile X male patients were investigated for seizures and EEG findings, 168 in a retrospective and 24 in another prospective study, to characterize the natural history of seizures, epilepsy, and EEG abnormalities in males with this syndrome. Seizures were documented in 35 (18.2%) of 192 patients; they never started before the age of 2 years or after the age of 9 years. Seizures were frequently of the complex partial type and less frequently of the partial motor and generalized type. Seizures involving frontal and temporal lobes were commonly seen and were usually well controlled by anticonvulsants. In the majority of young fragile X patients studied, an age-related paroxysmal EEG pattern was found, which showed neurophysiologic characteristics very similar to those of the centrotemporal spikes. These findings confirm that fragile X syndrome can be considered a genetic model of epilepsy.Epilepsia 09/1999; 40(8):1092-9. · 3.91 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Congenital cerebellar atrophy associated with a non-progressive cerebellar syndrome and mild cognitive retardation is described in seven cases, four of them familial. Their occurrence is consistent with an autosomal recessive inheritance. Clinical and neuroimaging data seem to exclude supratentorial changes. Even though it is not possible to definitely rule out a possible role of the forebrain in determining the mental defect, the neuropsychological study supplies arguments stressing the relationship between cerebellar defect and cognitive development.Brain and Development 01/1993; 15(6):439-45. · 1.67 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The authors report on seven patients, six males and one female, with Joubert's syndrome who underwent developmental evaluation, neurologic and ophthalmologic examinations, and magnetic resonance imaging of the brain. All patients had severe developmental delay, hypotonia, impairment of smooth visual pursuit, and saccadic eye movements. Six had jerky eye movements and ptosis was observed in two patients and retinal dystrophy in one. The posterior lobe of the vermis was absent in all patients and the small rudimentary anterior lobe lacked fusion in the midline, with cleft formation in five patients. Malformation of the pontomesencephalic junction, with prominent superior cerebellar peduncles and deep interpeduncular fossa, was observed in all patients. Abnormal cerebellar-brainstem and cerebellocortical connections because of the lack of the posterior vermis and dysplasia of the deep cerebellar nuclei might be responsible for the abnormal eye movements and retarded development in Joubert's syndrome. Correlation between radiologic findings and clinical symptoms and the possible role of abnormal patterning of the midbrain-hindbrain by homeotic genes during embryonic development are reviewed.Pediatric Neurology 05/1999; 20(4):274-81. · 1.42 Impact Factor