Brain magnetic resonance imaging findings in 49,XXXXY syndrome

Klinefelter syndrome is a chromosomal disorder characterized by one or more supernumerary X chromosomes, in addition to the normal 46,XY male karyotype. Whereas classic Klinefelter syndrome (47,XXY) occurs in 1:400 births, the most severe Klinefelter variant (49,XXXXY) occurs in only 1:85,000 births. The degree of cognitive impairment, specific skeletal changes, and genital abnormalities in Klinefelter syndrome variants is thought to correlate with the number of additional X-chromosomes present. Magnetic resonance imaging studies in individuals with classic Klinefelter syndrome show smaller brain volumes, but magnetic resonance imaging data are lacking for individuals with rarer and more severe Klinefelter variants. We present case reports and magnetic resonance imaging studies on 3 individuals with 49,XXXXY. All 3 patients exhibited varying degrees of volume loss and abnormalities in white matter. Changes in white matter may represent a specific finding in patients with severe Klinefelter variants such as 49,XXXXY, and karyotype analysis should be considered in patients with unexplained white-matter disease, especially when developmental delay or genital abnormalities are present.     

Further magnetic resonance imaging (MRI) brain delineation of 49,XXXXY syndrome

A rare sex chromosome aneuploidy syndrome, 49,XXXXY syndrome is characterized by mental retardation with severe learning difficulties, craniofacial and skeletal abnormalities, hypogonadism, and congenital heart disease. The authors describe a 30-month-old boy with 49,XXXXY syndrome, global developmental delay and white matter changes in the brain magnetic resonance imaging. They reviewed the literature to delineate a specific magnetic resonance imaging pattern of 49,XXXXY syndrome.     

Mild intellectual deficits in a child with 49,XXXXY

Severe mental retardation usually is present in males with a 49,XXXXY karyotype, although occasionally, intellectual functioning has been reported to be in the mild range of mental retardation. One child was previously described to have normal development at 15 months, but had mental retardation at 41 months. We present a male with 49,XXXXY who had mild-cognitive and motor delays and age-appropriate adaptive skills at 59 months. Greatest deficits were in expressive verbalizations similar to other male sex chromosome abnormalities. Mosaicism could not be demonstrated in blood or skin specimens. Although most males with 49,XXXXY syndrome will have significant mental retardation, findings in our patient and other reports suggest that variability in intellectual functioning may occur, in some instances, and may justify guarded optimism in affected males demonstrating close to or age-appropriate developmental skills through early childhood.     

Developmental outcome in 49,XXXXY Klinefelter syndrome.

The developmental histories of two males who have 49 XXXXY Klinefelter syndrome are described. Now aged 16 and six, they have been followed since the ages of four and two, respectively. They have many of the typical physical characteristics described in the literature, but their mental retardation is not as severe as has been reported. Both are moderately delayed in their general development and their personalities and learning styles are more similar to XXY Klinefelter individuals. These two case studies demonstrate previously unreported potential in individuals with this disorder, and the authors discuss the implications of this finding.     

The 49, XXXXY syndrome: clinical and psychological findings in five patients

ABSTRACT. In this study clinical and psychological findings arc presented in live 49.XXXXY patients. Their degree of mental retardation varied greatly, i.e. from moderalely to profoundly retarded. A decline in intelligence performance with age was obserived in one boy. Language developmenl was severely retarded with a remarkable discrepancy between language expression and comprehension. Emotional disturbances with low frustration level, timidity and shyness were noted in all live and their level of adaptive functioning was much higher than the cognitive level.     

A case of brain stem infarction with bilateral hearing impairment and tinnitus at the onset

We reported a 49-year-old male with brain stem infarction who had bilateral hearing impairment and tinnitus at the onset and subsequently developed various neurological symptoms, including bilateral lateral inferior pontine syndrome, one and a half syndrome and upward gaze palsy. Although CT scan failed to reveal any abnormalities initially, MRI revealed symmetrical foci bilaterally from the lateral inferior pons to the middle cerebellar peduncle, as well as in the paramedian portion of the mid-pons. Cerebral angiography: The left vertebral artery (VA) occluded at the 4th segment. The right VA showed severe stenosis at the 4th segment. The basilar artery (BA) was found to be occluded in the lower 1/3 below the clivus. Furthermore, CAG demonstrated upper portion of the BA, bilateral superior cerebellar artery and posterior cerebral artery via the posterior communicating artery, but the bilateral anterior inferior cerebellar arteries (AICAs) were absent or occluded. Neuroradiological findings suggested ischemia in the bilateral AICA and the middle portion of the BA. Bilateral hearing impairment rarely accompanies cerebrovascular disorders. This case of bilateral hearing impairment, tinnitus at the onset, followed by bilateral lateral inferior pontine syndrome was considered to be an extremely rare pathological condition.     

Down syndrome: a cardiovascular perspective

This review focuses on the heart and vascular system in patients with Down syndrome. A clear knowledge on the wide spectrum of various abnormalities associated with this syndrome is essential for skilful management of cardiac problems in patients with Down syndrome. Epidemiology of congenital heart defects, cardiovascular aspects and thyroid-related cardiac impairment in patients with Down syndrome will be discussed.     

Hearing and otologic disorders in children with Down syndrome

Hearing impairment and otologic problems have been reported to be prevalent among individuals with Down syndrome. This study was designed to determine whether children with Down syndrome have a higher prevalence of auditory abnormalities than do children with other forms of mental retardation. Hearing, impedance, and otoscopic examinations were performed on 30 children with Down syndrome and 30 children without Down syndrome matched for CA and IQ. Results indicated that the children with Down syndrome had a significantly higher prevalence of hearing impairment and otologic disorders.     

Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau-Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau-Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.     

Autosomal recessive ataxia, slow eye movements, dementia and extrapyramidal disturbances

An Arab family with an autosomal recessive form of spinocerebellar degeneration with slow eye movements is reported. Hitherto all the reported cases were either sporadic or of autosomal dominant inheritance. Associated are progressive intellectual impairment and extrapyramidal dysfunction as well as peripheral neuropathy and skeletal abnormalities. Muscle biopsy revealed non-specific mitochondrial abnormalities. The spectrum of eye movement abnormalities is discussed and the literature is reviewed. It is concluded that the hallmark of this syndrome (slow or even absent saccades) is one of a group of oculomotor abnormalities, all being characterized by delayed initiation and slow velocity. The syndrome seems to be related to the olivopontocerebellar degenerations, but differs in that there is in addition selective degeneration of certain tracts and nuclei in the mesencephalon and probably more rostral structures.     

The relationship between Usher's syndrome and psychosis with Capgras syndrome.

Usher's syndrome is a genetic disorder that causes congenital sensorineural hearing loss, visual impairment due to progressive pigmentary retinopathy, and, often, vestibular dysfunction. The aim of this article is to illustrate a case that clearly demonstrates psychotic symptoms in Usher's syndrome Type III and serves to increase clinical awareness of this disorder and its possible link to psychotic symptoms. There is some evidence in the literature of concurrent psychiatric symptoms, particularly psychotic symptoms, associated with Usher's syndrome, and several theories around this association have been proposed. These theories of associations include a genetic link between the genes responsible for schizophrenia and the genes for Usher's syndrome; a neuropathological explanation as radiologic studies have revealed that patients with Usher's syndrome have CNS abnormalities in multiple brain structures; and a sensory deficit model which proposes that the stressors associated with sensory impairment and the brain's adaptation to changes in sensory inputs place an individual at increased risk for psychopathology.     

Nocturnal epileptiform EEG discharges,nocturnal epileptic seizures,and language impairments in children: Review of the literature

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau–Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau–Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.     

Correlation of 1a afferent conduction with the ataxia of Fisher syndrome

The pathophysiology of the ataxia in Fisher syndrome (the syndrome of acute ophthalmoplegia, ataxia, and areflexia) has been attributed to both peripheral nervous system pathology and cerebellar system dysfunction. Pathologic studies have demonstrated no consistent central nervous system abnormalities. We present a case in which abnormalities of 1a sensory conduction were found to correlate directly with the degree of ataxia, without impairment of motor or cutaneous sensory conduction. We propose that the ataxia seen in typical Fisher syndrome may be due to demyelination of 1a afferent fibers.     

Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)

Smith-Magenis syndrome is a multiple congenital anomalies/mental retardation syndrome associated with a heterozygous deletion of chromosome 17p11.2. Seizures have not been formally studied in this population. Our objectives were to estimate the prevalence of seizures and electroencephalographic (EEG) epileptiform abnormalities in patients with Smith-Magenis syndrome with defined chromosomal rearrangements and to describe the spectrum of abnormal EEG patterns. Prolonged video-EEGs were obtained in 60 patients. Eighteen percent of patients reported a seizure history; however, abnormal EEGs were identified in 31 of the 60 subjects and 27 of 31 were epileptiform. Generalized epileptiform patterns were the most common (73%). Most patients with either small or large deletions had an abnormal EEG (83%; 75%) in contrast to those with a common deletion (49%). Our results indicate that epileptiform EEG abnormalities are frequent in patients with Smith-Magenis syndrome. Considering that close to one third of individuals with Smith-Magenis syndrome with epileptiform abnormalities also had a history of clinical seizures, cortical hyperexcitability and epilepsy should be considered an important component of the Smith-Magenis syndrome clinical phenotype.     

Prevalence of human immunodeficiency virus-associated cognitive impairment in a group of Hispanic women at risk for neurological impairment

Human immunodeficiency virus (HIV)-associated cognitive impairment, a significant cause of morbidity, affects up to 30% of HIV-infected people. Its prevalence doubled as patients began to live longer after the introduction of highly active retroviral therapy. Women are now one of the fastest growing groups with acquired immunodeficiency syndrome (AIDS) in the United States and Puerto Rico, but relatively little is known about the prevalence and characteristics of cognitive dysfunction in HIV-infected women. In this study the authors investigated its prevalence in a group of HIV-1-seropositive Hispanic women in Puerto Rico. Forty-nine women with a nadir CD4 cell count of < or = 500 cells/mm3 were enrolled. Cognitive impairment was defined according to the American Academy of Neurology criteria for HIV dementia as modified to identify an "asymptomatic cognitively impaired" group. Observed prevalence was compared with prevalence in other populations in United States, Europe, and Australia. Differences in clinical markers and neuropsychological test performance among the cohort stratified by cognitive impairment were tested. Cognitive impairment was observed in 77.6% (38/49) of cases; asymptomatic cognitive impairment in 32.7% (16/49); minor cognitive motor disorders in 16.3% (8/49); and HIV-associated dementia (HAD) in 28.6% (14/49). Cognitive impairment did not correlate with age, CD4 cell count, viral load, or treatment modality. The cross-sectional prevalence of HIV-associated cognitive impairment was 77.6% (28.6% for HAD). These findings should enhance awareness of the prevalence of HIV-associated cognitive impairment, both clinically apparent and "asymptomatic," in Hispanic women and lead to improvements in areas such as education and compliance and to reevaluation of treatment interventions.     

Acute encephalopathy in a patient with Dravet syndrome

Dravet syndrome (severe myoclonic epilepsy in infancy) is an epileptic syndrome with various types of seizures that begin in the first year of life and may result in intellectual impairment. Mutations of the SCN1A gene are the most prevalent genetic cause of Dravet syndrome. In this study, we report a 12-year-old girl with Dravet syndrome carrying an SCN1A mutation, c.2785Cdel (L929del fsX934). She had an episode of status epilepticus and persistent lethargy after 48 h of acute febrile illness that was preceded by an annual flu vaccination. Low voltage activities detected by electroencephalogram and elevated neuron-specific enolase/interleukin-6 concentrations in the cerebrospinal fluid suggested acute encephalopathy. MRI showed abnormalities in the bilateral thalami, cerebellum and brainstem. These abnormalities were protracted over a month. The biochemical and MRI characteristics of this case are different from any known type of encephalopathy, and may suggest a vulnerability of neurons expressing mutant SCN1A in the brain.     

Irreversible striatal neuroimaging abnormalities secondary to prolonged, uncontrolled diabetes mellitus in the setting of progressive focal neurological symptoms

Hemichorea–hemiballisum in patients with hyperglycemia and striatal hyperintensity on T1-weighted magnetic resonance imaging is now an accepted clinical entity. Usually, both the clinical syndrome and neuroimaging abnormalities are reversible. A transient, reversible metabolic impairment within the basal ganglion has been considered a possible cause of this disorder. However, the pathophysiology remains to be unclear. We report a 56-year-old man with a prolonged, uncontrolled hyperglycemia (HbA1C: 13.8%) and striatal hyperintensity on T1-weighted MR imaging presenting as reversible focal neurological deficit and irreversible neuroimaging abnormalities on the fourth month when blood sugar was under control (HbA1C 6.0 mg/dl). We hypothesize that neuroimaging abnormalities in our case may be a sequence of an “ischemic insult” caused by prolonged, uncontrolled hyperglycemia. Whether the signal abnormalities on neuroimaging studies or the clinical syndrome are reversible (patients with HCHB) or irreversible (such as in our case) are based on the degree of ischemic damage.     

The Sotos syndrome. Clinical and neuropsychiatric considerations in 1 case

A case of Sotos' syndrome or cerebral gigantism is described. The main clinical features of this syndrome are macrocrania, accelerated skeleton maturation and somatic development, cranio-facial dysmorfism, psychomotor retardation in 80% of the cases. Less frequently other skeleton abnormalities associated with neurological and/or endocrinological disorders are reported. In our patient the typical features of the syndrome are accompanied by several neurological signs (mental retardtion, strabism, hypothonia, motor impairment, seizures, CT scan abnormalities) and ophtalmological changes as optic disk pallor. The above mentioned range of symptoms should be considered as a direct consequence of the primary defect which characterizes the Sotos' syndrome. In our case the cerebral nervous system seems to be more specifically involved. Besides, important behavioural difficulties have emerged with regard to the double relation mother-daughter and in the familiar environment as well. For this reason we emphasize the necessity of evaluating and clearing up all problems which often arise in connection with various pathological conditions in childhood. This should be done in order to grant the families an appropriate support.     

Muenke syndrome

Background Muenke syndrome is a genetically determined craniosynostosis that involves one or both coronal sutures. In some patients it is associated with skeletal abnormalities such as thimble-like middle phalanges, coned epiphysis, and/or neurological impairment, namely sensorineural hearing loss or mental retardation. In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. Because of the incomplete penetrance of this anomaly, the suspicion of Muenke syndrome must be raised in any child with uni- or bilateral coronal craniosynostosis, and the genetic analysis propounded even in the absence of extracranial features.Illustrative cases We report the cases of two sisters who presented with Muenke syndrome and whose affected mother did not have any form of craniosynostosis.