Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromosome region 15q11q13 is known for its instability, and many rearrangements may occur in this imprinted segment: deletions associated either with Angelman syndrome (AS) or with Prader-Willi syndrome (PWS), according to parental origin; translocations; inversions; and supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) constitute the most common of the heterogeneous group of the extra structurally abnormal chromosomes, and their presence results in tetrasomy 15p and partial tetrasomy 15q. Inv dup(15), containing the Prader-Willi/Angelman syndrome region, are associated with altered behaviour, developmental delay/mental retardation, and seizures/epilepsy. Clinicians should suspect this syndrome in any infant/child with early central hypotonia, minor dysmorphic features, developmental delay, autism or autistic-like behaviour, and who subsequently develops hard to control seizures/epilepsy. Diagnosis is confirmed by standard cytogenetic techniques and FISH analysis. Although, about 100 cases have been reported to date, limited data are available on the natural history. To obtain better information on diagnosis and outcome in a clinical setting, we reviewed the available literature on clinical and behavioural phenotype of inv dup(15) syndrome.
 ...
PMID:The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. 1602 54

This study examined the nature and frequency of neurological and EEG abnormalities in 60 young children (ages 2-6 years) with pervasive developmental disorders. A number of standard neurological functions could not be adequately assessed due to the young age of the children and/or limited comprehension and cooperation. The most common neurological deficits were hyporeflexia, stereotypies, and hypotonia. EEG abnormalities were identified in 32% of the children while only two children were known to have clinical seizures. The frequency of cases with hypotonia or hyporeflexia was more common than in older children with this diagnosis. Results also indicate that EEG abnormalities are common in this young population but clinical seizures are rare, confirming other studies.
J Autism Dev Disord 2007 May
PMID:Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders. 1704 91

Deficiency of dihydropyrimidine dehydrogenase (DPD) is a rare inborn error of pyrimidine metabolism. To date, only about 50 patients are known worldwide. The clinical picture is varied and is not yet fully described. Most patients are diagnosed at the age of 1-3 years. We present a patient diagnosed 8 weeks postpartum. The female patient presented in the first 3 days after birth with agitation, choking, and vomiting. Six weeks later, the patient presented again with vomiting and insufficient weight gain. Metabolic screening of urine showed a strongly increased excretion of uracil and thymine, with no other abnormalities. This suggested a deficiency of DPD which was confirmed by enzyme analysis in peripheral blood mononucleair (PBM) cells (patient: activity <0.01 nmol/mg/h; controls: 9.9 +/- 2.8 nmol/mg/h). The patient was homozygous for the IVS14+1G>A mutation.MRI of the brain showed some cerebral atrophy; myelinization appeared normal. Many patients with DPD-deficiency suffer from convulsions and mental retardation, some show microcephaly, feeding difficulties, autism, and hypertonia. Our patient showed feeding difficulties and in the second half-year she developed slight motor retardation and generalized hypotonia. Further observation of the development of the patient may shed more light on the relationship between clinical symptoms and DPD deficiency. DPD deficiency may present in newborns with vomiting and hypotonia as the main symptoms.
 ...
PMID:A neonate with recurrent vomiting and generalized hypotonia diagnosed with a deficiency of dihydropyrimidine dehydrogenase. 1706 71

The Prader-Willi phenotype (PWP) of fragile X syndrome (FXS) is associated with obesity and hyperphagia similar to Prader-Willi syndrome (PWS), but without cytogenetic or methylation abnormalities at 15q11-13. Thirteen cases of PWP and FXS are reported here that were identified by obesity and hyperphagia. Delayed puberty was seen in 5 of 9 cases who had entered puberty, a small penis or testicles in seven of 13 cases, and infant hypotonia and/or a poor suck in seven of 13 cases. Autism spectrum disorder occurred in 10 of 13 cases, and autism was diagnosed in seven of 13 cases. We investigated cytoplasmic interacting FMR1 protein (CYFIP) expression, which is a protein that interacts with FMR1 protein (FMRP) because the gene for CYFIP is located at 15q11-13. CYFIP mRNA levels were significantly reduced in our patients with the PWP and FXS compared to individuals without FXS (p < .001) and also individuals with FXS without PWP (p = .03).
 ...
PMID:The Prader-Willi phenotype of fragile X syndrome. 1743 64

Autism spectrum disorders (ASD) are manifest as impairments in social interaction, language and speech development, and the appearance of repetitive behaviors with restricted interests. Motor impairments in individuals with ASD have been categorized as "associated symptoms". The objective of this study was to describe the prevalence of motor deficits in ASD. Specifically, using retrospective clinical record review, we report the prevalence of hypotonia, motor apraxia, reduced ankle mobility, history of gross motor delay, and toe-walking, as well as the improvement of these symptoms with age, in a cohort of 154 children with ASD. The possible association of motor deficits with epilepsy or developmental regression was also assessed. To address whether the motor deficits in children with ASD were properly identified and treated, we evaluated whether the children with the motor deficits were more likely to receive physical and/or occupational therapies as compared to the children with ASD who did not show motor deficits. Hypotonia was the most common motor symptom in our ASD cohort (51%) and this appeared to improve over time, as suggested by the significant reduction in prevalence in older children (p=0.002). Likewise, motor apraxia (34%) showed a tendency to be more prevalent among younger children as compared with older children (p=0.06). Historical intermittent toe-walking was found in 19% of children while reduced ankle mobility was a rare occurrence. Gross motor delay was reported in 9% of children, all of whom gained motor independence by the time of examination. Except for gross motor delay, ASD children with fine motor deficits were not more likely to receive interventional services, as compared with ASD children without the motor deficits. The results suggest that fine motor control and programming deficits are common co-occurrence of children with ASD in this cohort. The reduced prevalence of these motor deficits in older children suggests improvement over time, whether through natural progression, results of interventional therapy, or the combination of the two. However, ASD children with the motor deficits were not more likely to receive service than those without the motor deficits.
 ...
PMID:Prevalence of motor impairment in autism spectrum disorders. 1746 40

A central aspect of the cerebellar cognitive affective syndrome is the dysregulation of affect that occurs when lesions involve the 'limbic cerebellum' (vermis and fastigial nucleus). In this case series we describe neuropsychiatric disturbances in adults and children with congenital lesions including cerebellar agenesis, dysplasia, and hypoplasia, and acquired conditions including cerebellar stroke, tumor, cerebellitis, trauma, and neurodegenerative disorders. The behaviors that we witnessed and that were described by patients and families included distractibility and hyperactivity, impulsiveness, disinhibition, anxiety, ritualistic and stereotypical behaviors, illogical thought and lack of empathy, as well as aggression and irritability. Ruminative and obsessive behaviors, dysphoria and depression, tactile defensiveness and sensory overload, apathy, childlike behavior, and inability to appreciate social boundaries and assign ulterior motives were also evident. We grouped these disparate neurobehavioral profiles into five major domains, characterized broadly as disorders of attentional control, emotional control, and social skill set as well as autism spectrum disorders, and psychosis spectrum disorders. Drawing on our dysmetria of thought hypothesis, we conceptualized the symptom complexes within each putative domain as reflecting either exaggeration (overshoot, hypermetria) or diminution (hypotonia, or hypometria) of responses to the internal or external environment. Some patients fluctuated between these two states. We consider the implications of these neurobehavioral observations for the care of patients with ataxia, discuss the broader role of the cerebellum in the pathogenesis of these neuropsychiatric symptoms, and revisit the possibility of using cerebellar stimulation to treat psychiatric disorders by enhancing cerebellar modulation of cognition and emotion.
 ...
PMID:The neuropsychiatry of the cerebellum - insights from the clinic. 1778 22

The aim of this study was to categorize speech problems in autistic children in a manner allowing recognition of associated risk factors. We were specifically interested in the role of epilepsy and epileptiform activity in EEG in autistic patients since these dynamic processes can influence each other. We combined subtypes of autism with degrees of their functionality and we selected three speech endpoints: i) delayed development of speech, ii) complete mutism and iii) regression of speech. We retrospectively examined 205 autistic children (boys 145/70.7%, mean age 10 years). Median IQ was 55 (15;104) and median Childhood Autism Rating Scale (CARS) ranged within 38 (32;48). Univariate and multivariate logistic regression helped to define clinical and diagnostic factors that were significantly associated with speech endpoints. Epileptic seizures, epileptiform EEG abnormalities, non-right-handedness, hypotonia and severe decreased IQ score were found to be the most important mutually independent factors contributing to the increased risk of speech-related problems in patients with ASD.
 ...
PMID:Epilepsia, epileptiform abnormalities, non-right-handedness, hypotonia and severe decreased IQ are associated with language impairment in autism. 1831 96

The female carrier of a de novo interstitial deletion 9q [karyotype 46,XX,del(9)(q31.2q33.1)] was followed up over a period of more than 20 years. She shows facial dysmorphisms and significant growth retardation. Motor abilities are restricted by muscular hypotonia and malposition of the feet. She has mental retardation. There was no speech development and phases of autism were reported. By analyses with FISH and short tandem repeat markers, the interstitial deletion was confirmed and characterized to span 9q31.2q33.1, comprising at least 7.07 Mb. The aberration is of paternal origin.
 ...
PMID:Rare interstitial deletion 9q31.2 to q33.1 de novo: longitudinal study in a patient over a period of more than 20 years. 1838 7

Mutations in the AP1S2 gene, encoding the sigma1B subunit of the clathrin-associated adaptor protein complex (AP)-1, have been recently identified in five X-linked mental retardation (XLMR) families, including the original family with Fried syndrome. Studying four patients in two unrelated families in which AP1S2 nonsense and splice-site mutations segregated, we found that affected individuals presented, in addition to previously described features, with elevated protein levels in cerebrospinal fluid (CSF). Moreover, computed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels. Using the AP-2 complex, in which the sigma subunit is encoded by one single gene, as a model system, we demonstrated that sigma subunits are essential for the stability of human AP complexes. By contrast, no major alteration of the stability, subcellular localization, and function of the AP-1 complex was observed in fibroblasts derived from a patient carrying an AP1S2 mutation. Similarly, neither macro- nor microscopic defects were observed in the brain of an affected fetus. Altogether, these data suggest that the absence of an AP-1 defect in peripheral tissues is due to functional redundancy among AP-1 sigma subunits (sigma1A, sigma1B, and sigma1C) and that the phenotype observed in our patients results from a subtle and brain-specific defect of the AP-1-dependent intracellular protein traffic.
 ...
PMID:Clinical, cellular, and neuropathological consequences of AP1S2 mutations: further delineation of a recognizable X-linked mental retardation syndrome. 1842 3

The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (CGH) is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy). Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements. Individuals with deletion 22q13 should have routine examinations by the primary care physician as well as genetic evaluations with referral to specialists if neurological, gastrointestinal, renal, or other systemic problems are suspected. Affected individuals benefit from early intervention programs, intense occupational and communication therapies, adaptive exercise and sport programs, and other therapies to strengthen their muscles and increase their communication skills. No apparent life-threatening organic abnormalities accompany the diagnosis of deletion 22q13.
 ...
PMID:Deletion 22q13.3 syndrome. 1850 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>