成年型孪生子Moyamoya病

目的报道一个成年型孪生子Moyamoya病。方法孪生姊妹之一的先证者为31岁,1年前出现全身乏力,检查发现糖尿病。半年前出现性格改变和抑郁,5个月前出现发作性右上肢麻木无力,2个月前出现左上肢活动不灵活和双下肢一过性无力,6d前出现大小便失禁和精神行为异常。查体显示轻度痴呆,左侧鼻唇沟浅,四肢肌力级,肌张力高,四肢锥体束征阳性。头部CT显示大脑半球多发性脑梗死。另一孪生妹妹在2年前亦发现糖尿病,曾经有过头晕发作。对先证者进行TCD和脑血管造影检查,另一孪生妹妹和无症状的2个哥哥及一对孪生女儿进行TCD检查。结果先证者DSA检查示双侧颈内动脉闭塞,双侧大脑前、中动脉主干不显影,颅底可见异常增生的血管网。TCD检查显示先证者和孪生姊妹的双侧颈内动脉末端闭塞,后循环代偿性血流增快,其孪生女儿之一存在双侧大脑中动脉起始段狭窄,无症状的2个哥哥血管无异常。结论孪生子Moyamoya病可以在成年起病,以缺血性损害为主要临床表现,合并糖尿病提示该类型Moyamoya病的发生可能和糖尿病相关基因的异常有关。当双胞胎之一出现Moyamoya病时,对另一个成员应当常规进行TCD筛查以确定其血管是否存在异常。     

The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome

A gene for Methyl-CpG binding protein 2 (MECP2), which locates Xq28, was recently found to be responsible for Rett syndrome. Although mutational analyses of MECP2 in Rett syndrome have been extensively analyzed, the mechanism(s) by which variable clinical phenotype occurred between affected monozygotic twins or sisters have not been clarified. We hypothesized that the difference of X-inactivation pattern might explain this phenomenon. With the method based on methylation-specific PCR, we analyzed polymorphic trinucleotide repeat in the human andorogen receptor gene mapped on Xq11.2-12, using DNA samples derived from previously described monozygotic twins and sisters together with their parents. Their clinical phenotypes were reported to be significantly different between siblings. We found that (1) maternally derived allele is predominantly active than paternally derived one in three out of four patients analyzed, (2) remaining one twin patient, whose ratio of active paternal allele is almost the same level as maternal allele, showed far much severe phenotype when compared with her counterpart. Together with the finding that most of the alleles with de novo mutation are from paternal X chromosome in sporadic cases, the existence of a mechanism that suppresses mutated paternal allele activation, resulting skewed X-inactivation to make clinical phenotype milder, might be speculated. Thus, when this mechanism fails to work sufficiently by an unknown reason, severer clinical phenotype could occur.     

Myasthenia gravis in monozygotic twins. Clinical follow-up nine years after thymectomy

Genetically proved monozygotic female twins in whom myasthenia gravis developed in their 20s initially had their disease well controlled with anticholinesterase medication. Because of increasing resistance to medication, twin 1 had her thymus removed, after which the symptoms decreased. Predicated on the improvement in her sister and the need for increasing medication to allay symptoms, and after proof of monozygosity, twin 2 also underwent thymectomy, with subsequent symptomatic improvement. The twins were followed up nine and six years after thymectomy, respectively. Monozygotic twins with myasthenia gravis are generally young women, with onset of disease in one occurring within one to three years of the other. Reports of only one affected twin may be misleading because of inadequate documentation of monozygosity, absence of long-term observation, or both. Serial investigations of the "uninvolved" twin in a monozygous pair and proof of monozygosity should be obtained to aid in early diagnosis and treatment of this illness, as well as to study the pathogenesis of myasthenia gravis prior to symptom onset.     

Narcolepsy: a family study.

We obtained medical and psychological assessments and 48-hr polysomnographic recordings on five sisters, three of whom had narcolepsy. Of the three, two were identical twins. All three narcoleptic sisters cited emotional stress and environmental demands for sustained performance as the major factors which aggravated their symptoms, and corresponding to this, the illness followed a different life course in each of the three. Most striking were the differences between the twin sisters in clinical symptoms and polysomnographic signs. One sister suffered from all the symptoms of narcolepsy and her sleep recording showed the typical sleep onset REM periods of the disease. Her twin suffered only from excessive daytime drowsiness and her sleep recording was normal--at least by the usual criteria. The sleep of all three narcoleptic sisters, however, was significantly more fragmented than that of their normal siblings. Our data suggested that excessive sleep fragmentation was a basic feature of narcolepsy and that it betrayed a constitutional predisposition for sleep to dissociate into its components and to become distributed around the nycthemeron. This process could be aggravated by emotional stress and by environmental demands for sustained vigilance, and this in turn, created the differences in symptoms and signs between individuals with identical genetic predispositions.     

Monozygous twins discordant for amyotrophic lateral sclerosis

A pair of identical female twins were discordant for amyotrophic lateral sclerosis. The affected twin was not breast-fed; was bitten by a poisonous snake, and was operated on for struma. She had more infections than her sister but no fractures. Her plasma insulin response to glucose loading was also higher. The twins lived separated in their early childhood.     

Adrenomyeloneuropathy: a form of X-linked adrenoleukodystrophy. Report of a family

A family with adrenoleucodystrophy linked to chromosome X (X-ALD) is reported. Three patients, one man (proband) and two female monozygotic twins, had adrenomyeloneuropathy (AMN) which is a form of the disease. The proband had characteristic changes in MRI with demyelination of the white matter in the cerebral hemispheres. Both women (one of them was proband's mother) has somewhat less severe AMN form, but in her twin sister the syndrome was much more intense. The clinical diagnosis of the disease was confirmed by biochemical investigations--determination of the level of very long chain fatty acids, ALDP protein and the activity of peroxysomal beta-oxidation.     

Alzheimer''s disease in one monozygotic twin

A woman of 64 died after an illness lasting 15 years and characterized by a progressive amnesic syndrome followed by global dementia. The brain showed changes typical of Alzheimer's disease. Her monozygotic twin sister was clinically not affected and died two years later of carcinoma. This is the second report of monozygotic twin sisters apparently discordant for presenile dementia of Alzheimer type.     

Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism

OBJECTIVE: The broader autism phenotype includes relatives of individuals with autism who display social and language deficits that are qualitatively similar to those of autism but less severe. In previous studies of monozygotic twins discordant for autism, more than 75% of the twins without autism displayed the broader phenotype. Differences in neuroanatomy between discordant monozygotic twins might be associated with the narrow and broader behavioral phenotypes. The authors examined the relationship of twin pair differences in clinical phenotype to differences in neuroanatomic phenotype. METHOD: The subjects were 16 monozygotic twin pairs between the ages of 5 and 14 years and 16 matched singleton comparison subjects. Seven twin pairs were clinically concordant and nine twin pairs were clinically discordant for strictly defined autism. After magnetic resonance imaging, a semiautomated procedure was applied to images in which the brain tissue was subdivided into neurofunctional regions and segmented into gray, white, and ventricular compartments. RESULTS: Both the concordant and discordant twin pairs exhibited concordance in cerebral gray and white matter volumes. However, only the clinically concordant pairs exhibited concordance in cerebellar gray and white matter volumes. Within the discordant twin pairs, both the twins with autism and their co-twins exhibited frontal, temporal, and occipital white matter volumes that were lower than those of the comparison subjects. CONCLUSIONS: These findings support the role and the limits of genetic liability in autism. Continuing to clarify the neuroanatomic pathways in autistic spectrum disorders could illuminate the etiology of autism and, ultimately, contribute to treatments.     

Neuroanatomical and neurocognitive differences in a pair of monozygous twins discordant for strictly defined autism

In this study, we investigated the neuroanatomical similarities and differences between a pair of monozygotic, 7.5-year-old twin boys discordant for strictly defined autism, to identify neuroanatomical pathways that are impaired in individuals with autism. Although the unaffected twin did not fulfill the traditional diagnostic criteria for autism, he displayed constrictions in social interaction and play that were consistent with the broader phenotype for autism that has been described in nonautistic co-twins. Magnetic resonance imaging scans were obtained for each brother and compared with the scans of 5 age- and sex-matched unaffected peers. Quantitative analysis of brain anatomy revealed that the affected twin had markedly smaller caudate, amygdaloid, and hippocampal volumes, and smaller cerebellar vermis lobules VI and VII, in comparison with his brother. Both twins evidenced disproportionately reduced volumes of the superior temporal gyrus and the frontal lobe relative to the comparison sample. The results suggest the dysfunction of two separate but overlapping neuroanatomical pathways, ie, one subcortical network differentiating the twins from each other that may underlie the traditional neurobehavioral phenotype for strictly defined autism, and a second cortical network differentiating the twins from the comparison sample that may lead to the broader phenotype for autism.     

Myasthenia gravis occurring in twins

Myasthenia gravis in one member each of two sets of twins is described. A 17 year old girl developed generalized myasthenia gravis at the age of 14 years, while her monozygotic twin sister has remained in good health during a three year period of observation. Another patient was a 19 year old woman with the onset of generalized myasthenia gravis at the age of 11 years, and her dizygotic twin sister has been in good health.     

Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals.

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS.     

Juvenile parkinsonism in monozygotic twins

A pair of monozygotic twins concordant for juvenile Parkinsonism are described. These twin sisters have lived together until 18 years old. Twin A noted tremor in the right hand and right-sided stiffness and slowness at the age 20. Initially, a marked improvement was shown with L-dopa treatment. However, one year after the beginning of treatment, dopa-induced dyskinesia appeared. Twin B noted tremor and right-sided stiffness and basal ganglia calcification in both patients. These twin patients suggest that genetic factors may play an important role in the cause of juvenile Parkinsonism.     

IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study

Williams syndrome (WMS), a genetic condition resulting from a contiguous deletion on the long arm of chromosome 7, is associated with a relatively consistent profile of neurocognitive and neurobehavioral features. The distinctiveness and regularity of the profile of learning and behavioral characteristics in this genetic condition suggests that underlying neurobiological correlates may be identifiable. In this initial study, we report findings derived from a high-resolution neuroimaging study of 14 young adult subjects with WMS and an individually matched normal control group. Compared to controls, subjects with WMS were noted to have decreased overall brain and cerebral volumes, relative preservation of cerebellar and superior temporal gyrus (STG) volumes, and disproportionate volume reduction of the brainstem. Analyses also suggested that the pattern of cerebral lobe proportions in WMS may be altered compared to normal controls with a greater ratio of frontal to posterior (parietal+occipital) tissue. Assessment of tissue composition indicated that, relative to controls, individuals with WMS have relative preservation of cerebral gray matter volume and disproportionate reduction in cerebral white matter volume. However, within the cerebral gray matter tissue compartment, the right occipital lobe was noted to have excess volume loss. Combined with our growing knowledge of the function of genes in the commonly deleted region for WMS, more detailed information regarding the structure and function of the WMS brain will provide a unique opportunity for elucidating meaningful correlations amongst genetic, neurobiological, and neurobehavioral factors in humans.     

Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome.

BACKGROUND: Turner syndrome (TS) results from complete or partial monosomy X. The cognitive phenotype of TS involves preservation of verbal skills with visuospatial functioning deficits. The superior temporal gyrus (STG), which is involved in language capacities, has not been investigated in TS. METHODS: The STG was measured in 30 female subjects (mean age = 14.73 +/- 6.41; range = 7.56-33.30) with TS and 30 age-matched control subjects (mean age = 14.63 +/- 5.90; range = 6.35-32.65) using volumetric magnetic resonance imaging analyses. RESULTS: -Right STG, including both gray and white matter volumes, was significantly larger in TS compared with control subjects. Overall left STG volume was not significantly different between groups, although left white matter volume was increased in the TS subjects. The TS subgroup with a maternally derived X chromosome (Xm) demonstrated more aberrant STG volumes compared with subjects with a paternally (Xp) derived X and control subjects. The difference in STG volumes between Xm and control subjects involved both white and gray matter. The Xm subjects differed from Xp subjects only in terms of gray matter. CONCLUSIONS:These findings suggest that X-monosomy and X-linked imprinting negatively affect STG development, possibly by disrupting neural pruning mechanisms.     

The Fragile-X syndrome in twin sisters

ABSTRACT. Two mentally handicapped dizygotic twin sisters were found to possess the Fragile-X lesion. They showed different levels of cognitive deficit. The hypothesis that the level of cognitive function in female carriers of the Fragile-X lesion may be influenced by Lyonization is discussed. The mother of the twins was schizophrenic. Although she was an obligate carrier her psychosis was thought not to be causally connected with the Fragile-X status.     

White matter volume as a major predictor of cognitive function in Sturge-Weber syndrome

OBJECTIVE: To assess the role of gray and white matter volume loss vs seizures in cognitive impairment of children with Sturge-Weber syndrome with unilateral involvement. DESIGN: Patients were enrolled in this prospective cohort during a period of 3 years. SETTING: Pediatric neurology clinic with national referral through the Sturge-Weber Foundation. PARTICIPANTS: Twenty-one children (age range, 1 year 6 months to 10 years 4 months) with unilateral Sturge-Weber syndrome. MAIN OUTCOME MEASURES: Cortical gray matter and hemispheric white matter volumes were measured on segmented volumetric magnetic resonance imaging and correlated with the age of the participants. Global intellectual function (IQ) was correlated with magnetic resonance imaging and seizure variables in both univariate and multivariate analyses. RESULTS: Both gray and white matter volumes showed an age-related linear increase. Tissue volumes on the side of the angioma showed a positive correlation with IQ after controlling for age in univariate regression analyses (white matter, r = 0.71, P < .001; gray matter, r = 0.48, P = .03), while seizure variables did not correlate with IQ (P > .1). A multivariate regression showed that hemispheric white matter volume ipsilateral to the angioma was an independent predictor of IQ (R = 61, P = .006), which also showed a negative correlation with age (R = - 0.52, P = .022) but no correlation with gray matter volumes. CONCLUSIONS: Early hemispheric white matter loss may play a major role in cognitive impairment in children with Sturge-Weber syndrome. Future therapeutic approaches should aim at preserving white matter integrity in addition to seizure control to improve cognitive outcome.     

Decreased levels of soluble amyloid β-protein precursor are associated with Alzheimer's disease in concordant and discordant monozygous twin pairs

We conducted immunochemical measurements of soluble amyloid β-protein precursor (βPP) in cerebrospinal fluid (CSF) from three monozygous twin pairs. Two of the twin pairs are discordant for Alzheimer's disease and one pair showed concordance for Alzheimer's disease, which was confirmed neuropathologically. All affected individuals displayed substantially lower levels of soluble βPP in CSF compared with the unaffected individuals. There were no differences in total protein levels in CSF samples from the affected twins compared with those of the unaffected twins. These studies suggest that decreased soluble βPP in CSF may reflect neuropathological processes in Alzheimer's disease involving βPP.     

Risk analyses for the cognitive phenotype in Turner's syndrome: evidence of familial influence as a decisive factor

The interindividual varying cognitive performance in female patients with Turner's syndrome has usually been attributed to the interindividual varying mosaicism with a consecutive variable loss of X-chromosome DNA or to secondary risk factors such as estrogen deficiency owing to ovarian failure. The aim of our study was to determine the specific impact of X chromosome-related features and associated risk factors, on the one hand and familial influences, on the other hand on the interindividual variation in the cognitive phenotype. One hundred and one subjects with Turner's syndrome and 53 sisters as controls for familial influences were examined by comparing the cognitive information processing abilities (Kaufmann Assessment Battery for Children [K-ABC]). Subjects with Turner's syndrome performed at a significantly lower level than sisters on all subscales (eg, Mental Processing Composite: Turner's syndrome 86.4 [SD 15.0] versus sisters 99.3 [SD 10.6]; P < .001). For the neurocognitive phenotype in subjects with Turner's syndrome, a significant correlation was found only with the sisters' cognitive abilities (Mental Processing Composite: r = .38, P < .05). In contrast, neither the individual mosaic status nor the known associated risk factors predicted the neurocognitive phenotype in Turner's syndrome. These results are corroborated in the regression analyses in those subjects with Turner's syndrome with a sister (Simultaneous Processing(sister) for Simultaneous Processing(Turner's syndrome): beta = .346, P < .05, corrected R2 = .049; and Mental Processing Composite(sister) for Mental Processing Composite(Turner's syndrome): beta = .354, P < .05, corrected R2 = .033). The interindividual variation of intellectual abilities in Turner's syndrome seems to be primarily related to familial coinfluences and not to the interindividual varying loss of X-chromosome DNA in terms of hidden mosaicism or potential associated risk factors.     

Synaesthesia: A Case Study of Discordant Monozygotic Twins

We describe a study of 11-year-old twin sisters who are physically identical in appearance but who have considerably different conscious experiences. One twin appears to be a synaesthete in that she states that she has specific colour experiences (i.e. photisms) whenever she views, hears or thinks of digits. The other twin does not report such conscious experiences when viewing, hearing or thinking about digits. A genotypic analysis using eight microsatellite loci plus the gender of the twins and their parents confirmed that the twins are monozygotic. A phenotypic analysis using a modification of the Stroop task confirmed that only one twin is a synaesthete. We suggest that the discordance in synaesthesia may be due to either an epigenetic event, X chromosome inactivation, or a mutation of a synaesthesia gene.     

Brain development in Turner syndrome: a magnetic resonance imaging study

Turner syndrome (TS) results from the absence of an X chromosome in females. This genetic condition is associated with specific cognitive deficits and variations in brain volumes. The goal of this study was to use high-resolution magnetic resonance imaging (MRI) to determine morphological variations in TS and to investigate the effects of parental origin of the X chromosome on brain development in TS. MRI brain scans were acquired from 26 girls with TS and 26 age- and gender-matched controls. Seventeen of the TS subjects had a maternally inherited X chromosome (Xm), and nine of the subjects had a paternally inherited X chromosome (Xp). Rater-blind morphometric analyses were conducted to compare tissue volume differences between girls with TS and controls. Three-way analyses were used to compare subgroups and controls. Subjects with TS demonstrated bilateral decreases in parietal gray and occipital white matter accompanied by increased cerebellar gray matter. Subjects with Xm showed decreased occipital white matter and increased cerebellar gray matter compared to controls. No differences were found in comparisons between subjects with Xp and controls or between subjects with Xm and Xp. Results suggest that X monosomy affects posterior cerebral and cerebellar anatomy in TS. While differences between comparisons of Xm and Xp to controls might suggest an imprinting effect, no significant differences were found when the two subgroups were directly compared to each other. Further investigation into the possible role of genomic imprinting is therefore warranted.