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1.
Mol Genet Genomic Med ; 9(12): e1780, 2021 12.
Article in English | MEDLINE | ID: mdl-34369668

ABSTRACT

BACKGROUND: Phelan-McDermid syndrome (PMD) is usually not only caused by 22q13.3 deletion but also pathogenic variants (mutations) of SHANK3 gene. PMD is characterized by global intellectual disability, severely delayed or absent speech, and features of autism spectrum disorder and susceptibility to psychotic behavior. Here, we describe a neurocognitive follow-up and genetic etiology for two siblings with PMD. METHOD: Comparative genomic hybridization (CGH) array test was normal and no 22q13.3 deletion was observed. For this reason, whole exome sequencing (WES) analyzed the siblings' and the parents' DNA sample. RESULTS: The results of the siblings strongly suggest that the SHANK3 gene variant c.2313+1G>A is pathogenic and PMD can be inherited from a mosaic father for this gene variant. Both siblings learned new skills until puberty but experienced a neuropsychiatric disaster after the age of 14 years experienced neurocognitive decline and it was sharp for one of the siblings. CONCLUSION: The long-term observations are sparse in PMD and SHANK3 mutations. This is the neurocognitive follow-up from childhood to middle ages, where a sharp neurocognitive decline was observed. We conclude that progressive neuropsychiatric symptoms in adolescence are a universal clinical clue for PMD diagnosis and an underlying SHANK3 splicing site mutation.


Subject(s)
Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Mutation , Nerve Tissue Proteins/genetics , Phenotype , RNA Splice Sites , Siblings , Adult , Aged , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 22/genetics , Comparative Genomic Hybridization , Female , Follow-Up Studies , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Mental Status and Dementia Tests , Exome Sequencing
2.
J Appl Res Intellect Disabil ; 33(5): 1113-1118, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32281257

ABSTRACT

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. The aim of our longitudinal study was to describe ageing-related cognitive changes in men with FXS. METHOD: A neuropsychologist determined the raw scores (RSs) of 19 men with FXS twice with the Leiter International Performance Scale at an average interval of 22 years. The ages of the participants at baseline ranged from 16 to 50 (mean 27) years. RESULTS: At follow-up, the RSs improved in two men, remained the same in two men and declined in 15 men. Overall, the RS of the study group deteriorated by an average 4 points in RSs (p < .001). CONCLUSION: Cognitive ageing in men with FXS started earlier than that in men in the general population; in many cases, cognitive ageing in men with FXS began before middle age, usually without any medical or other underlying cause.


Subject(s)
Fragile X Syndrome , Intellectual Disability , Adolescent , Adult , Aging , Cognition , Humans , Longitudinal Studies , Male , Middle Aged , Young Adult
3.
Mol Genet Genomic Med ; 7(6): e695, 2019 06.
Article in English | MEDLINE | ID: mdl-31033253

ABSTRACT

BACKGROUND: Williams syndrome (WBS) is a genetic multisystem disorder. The main symptom is borderline (intelligence quotient, IQ 70-79) or abnormally low intelligence (IQ < 70). According to earlier studies young individuals with WBS demonstrate generally a slightly higher verbal IQ (VIQ) compared to performance/nonverbal IQ (PIQ). WBS was recognized as a distinct entity already about 60 years ago, but still cognition in adults with WBS is poorly known. METHODS: We followed 25 adults (age at baseline 19-68, median 38) with genetically confirmed WBS for about 20 years. The study subjects underwent medical and neuropsychological assessments at the baseline and at the end of follow-up. RESULTS: The mean VIQ remained quite stable from early adulthood up to 40 years of age after which it declined. The mean PIQ kept on improving from early adulthood until 50 years of age after which it gradually declined. At the end of the study, all study subjects had at least two longstanding health problems out of which hypertension, psychiatric disorder, and scoliosis or kyphosis occurred most frequently. At end of the study, two patients suffered from vascular dementia. Seven patients died during the follow-up. CONCLUSIONS: In adults with WBS, the course of cognition is uneven across the cognitive profile. Their verbal functions both develop and deteriorate earlier than performance/nonverbal functions. Frequent somatic co-morbidities may increase risk to shortened life span.


Subject(s)
Cognition , Williams Syndrome/physiopathology , Adult , Aged , Female , Humans , Language , Male , Middle Aged
4.
Mol Genet Genomic Med ; 6(5): 855-860, 2018 09.
Article in English | MEDLINE | ID: mdl-29971948

ABSTRACT

BACKGROUND: Intellectual disability (ID) and dementia reflect disturbed cortical function during and after developmental age, respectively. Due to the wide heterogeneity of ID population the decline in cognitive and adaptive skills may be different in distinct genetic subgroups. METHODS: Using the British Present Psychiatric State-learning Disabilities assessment (PPS-LD) questionnaire the dementia signs were screened in 62, 22 and 44 individuals (> 35 year of age) with Down (DS, OMIM number 190685), Williams (WS, OMIM number, 194050), and Fragile X syndrome (FXS, OMIM number 309550), respectively. The median age of those with FXS (59 years) was higher than of those with DS (50 years) and WS (53 years). RESULTS: Most study participants with DS (80%) and FXS (89%) were or had been moderately or severely intellectually disabled while most participants with WS (73%) were or had been mildly or moderately disabled at adolescent age. The adolescent (premorbid) level of ID did not correlate with the dementia score. The median scores were 11/27, 1/27, and 0/27 in DS, WS, and FXS subgroups, respectively. Dementia that was confirmed by brain imaging, manifested as Alzheimer disease and as moya-moya disease associated vascular dementia in DS and as vascular dementia in WS. CONCLUSIONS: This survey suggests that the risk of dementia varies depending on the cause of ID and that the severity of ID in adolescence does not predict the development of dementia at a later age. Consequently, the ID and dementia should be understood as separate clinical entities that need to be taken into account in the health management of intellectually disabled people. This is important for the arrangement of appropriate and timely interventions, which can be expected to delay the need for institutionalization.


Subject(s)
Dementia , Down Syndrome , Fragile X Syndrome , Williams Syndrome , Adult , Aged , Dementia/epidemiology , Dementia/physiopathology , Down Syndrome/epidemiology , Down Syndrome/physiopathology , Female , Fragile X Syndrome/epidemiology , Fragile X Syndrome/physiopathology , Humans , Male , Middle Aged , Risk Factors , Williams Syndrome/epidemiology , Williams Syndrome/physiopathology
5.
SAGE Open Med Case Rep ; 6: 2050313X18777951, 2018.
Article in English | MEDLINE | ID: mdl-29844915

ABSTRACT

We describe here the clinical outcome of four women with epilepsy with eyelid myoclonia (aged 21-53 years). All patients had an uneventful early history, normal physical growth and appearance and no comorbid sensory or motor disability and normal brain magnetic resonance imaging finding. Two women were moderately and one mildly intellectually disabled and one showed a low-average intelligence. The overall well-being of the patients was hampered by psychiatric or various somatic comorbidities and related psychosocial problems. The three women with an intellectual disability had been treated with narrow-spectrum antiepileptic drugs and one also with vigabatrin during childhood and adolescence. The patient with a low-average intelligence had been on broad-spectrum antiepileptic medication (i.e. valproate and ethosuximide) since the epilepsy diagnosis but she has had compliance problems. Based on these cases, the cognitive deficits in patients with epilepsy with eyelid myoclonia may occur more commonly than what has been thought hitherto. We discuss the role of narrow-spectrum antiepileptic drugs as a contributing factor to poor seizure control and an impaired intelligence.

6.
Neuroimage ; 35(4): 1547-50, 2007 May 01.
Article in English | MEDLINE | ID: mdl-17363283

ABSTRACT

Down syndrome (DS) is characterized by intellectual disability and development of dementia that are attributed to similar neuropathological features as observed in Alzheimer's disease (AD). The aim of this study was to investigate whether DS patients have similar impairment of preattentive auditory processing as observed in AD. Sinusoidal tones were presented to DS patients and healthy controls, and evoked auditory evoked fields (AEF) were measured with a whole-head magnetoencephalography (MEG) system. Patients with DS had significantly delayed and attenuated N100m, and delayed but not attenuated P50m responses over both hemispheres. Present results indicate that preattentive auditory processing underlying stimulus detection is impaired in DS. Given that anticholinergic drugs modulate AEFs, degeneration of cholinergic system in DS could contribute to the damaged auditory processing.


Subject(s)
Auditory Perception/physiology , Down Syndrome/physiopathology , Down Syndrome/psychology , Acoustic Stimulation , Adult , Electrooculography , Evoked Potentials, Auditory/physiology , Female , Functional Laterality/physiology , Humans , Intelligence/physiology , Magnetoencephalography , Male , Memory/physiology , Middle Aged
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