Alström Syndrome Associated With Cerebral Involvement: An Unusual Presentation

Yılmaz, Cahide; Çaksen, Hüseyîn; Yılmaz, Nebi; Güven, Ahmet Sami; Arslan, Derya; Cesur, Yaşar

doi:10.29333/ejgm/82358

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…Brain involvement was reported in a 6-year-old girl with AS presenting with aphasia since birth and mild right hemiparesis noted three months before admission [8]. Her brain CT revealed atrophy of the left hemisphere, that according to the authors could have been a coincidental association.…”

Section: Discussionmentioning

confidence: 92%

Brain involvement in Alström syndrome

Citton

Favaro

Bettini

et al. 2013

Orphanet Journal of Rare Diseases

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BackgroundAlström Syndrome (AS) is a rare ciliopathy characterized by cone–rod retinal dystrophy, sensorineural hearing loss, obesity, type 2 diabetes mellitus and cardiomyopathy. Most patients do not present with neurological issues and demonstrate normal intelligence, although delayed psychomotor development and psychiatric disorders have been reported. To date, brain Magnetic Resonance Imaging (MRI) abnormalities in AS have not been explored.MethodsWe investigated structural brain changes in 12 genetically proven AS patients (mean-age 22 years; range: 6–45, 6 females) and 19 matched healthy and positive controls (mean-age 23 years; range: 6–43; 12 females) using conventional MRI, Voxel-Based Morphometry (VBM) and Diffusion Tensor Imaging (DTI).Results6/12 AS patients presented with brain abnormalities such as ventricular enlargement (4/12), periventricular white matter abnormalities (3/12) and lacune-like lesions (1/12); all patients older than 30 years had vascular-like lesions. VBM detected grey and white matter volume reduction in AS patients, especially in the posterior regions. DTI revealed significant fractional anisotropy decrease and radial diffusivity increase in the supratentorial white matter, also diffusely involving those regions that appeared normal on conventional imaging. On the contrary, axial and mean diffusivity did not differ from controls except in the fornix.ConclusionsBrain involvement in Alström syndrome is not uncommon. Early vascular-like lesions, gray and white matter atrophy, mostly involving the posterior regions, and diffuse supratentorial white matter derangement suggest a role of cilia in endothelial cell and oligodendrocyte function.

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Section: Discussionmentioning

confidence: 92%

Brain involvement in Alström syndrome

Citton

Favaro

Bettini

et al. 2013

Orphanet Journal of Rare Diseases

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“…Deficits in cerebellar areas are known to relate to deficits in EF ( Cardoso et al, 2014 ) and individuals with higher EF have been shown to have greater recruitment of cerebellar regions within a fronto-parietal resting state network ( Reineberg et al, 2015 ). Cerebellar anomalies have in fact been observed in individuals with AS ( Yilmaz et al, 2006 ), but no consistent findings in these areas have been discovered in the AS population ( Citton et al, 2013 ). Thus, individual cerebellar anomalies may account for some of the EF deficit found in individuals with AS in the present study.…”

Section: Discussionmentioning

confidence: 98%

Theory-of-mind in individuals with Alström syndrome is related to executive functions, and verbal ability

Frölander¹,

Möller²,

Rudner³

et al. 2015

Front. Psychol.

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Objective: This study focuses on cognitive prerequisites for the development of theory-of-mind (ToM), the ability to impute mental states to self and others in young adults with Alström syndrome (AS). AS is a rare and quite recently described recessively inherited ciliopathic disorder which causes progressive sensorineural hearing loss and juvenile blindness, as well as many other organ dysfunctions. Two cognitive abilities were considered; Phonological working memory (WM) and executive functions (EF), both of importance in speech development.Methods: Ten individuals (18–37 years) diagnosed with AS, and 20 individuals with no known impairment matched for age, gender, and educational level participated. Sensory functions were measured. Information about motor functions and communicative skills was obtained from responses to a questionnaire. ToM was assessed using Happés strange stories, verbal ability by a vocabulary test, phonological WM by means of an auditory presented non-word serial recall task and EF by tests of updating and inhibition.Results: The AS group performed at a significantly lower level than the control group in both the ToM task and the EF tasks. A significant correlation was observed between recall of non-words and EF in the AS group. Updating, but not inhibition, correlated significantly with verbal ability, whereas both updating and inhibition were significantly related to the ability to initiate and sustain communication. Poorer performance in the ToM and EF tasks were related to language perseverance and motor mannerisms.Conclusion: The AS group displayed a delayed ToM as well as reduced phonological WM, EF, and verbal ability. A significant association between ToM and EF, suggests a compensatory role of EF. This association may reflect the importance of EF to perceive and process input from the social environment when the social interaction is challenged by dual sensory loss. We argue that limitations in EF capacity in individuals with AS, to some extent, may be related to early blindness and progressive hearing loss, but maybe also to gene specific abnormalities.

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“…Some individuals lack facial movement sometimes associated with speech difficulty [ 62 ]. Cerebellar anomalies have been noted [ 64 ]. Although there are some individuals with Alström syndrome that seem to be totally free of psychological issues, major depression, obsessive-compulsive behavior, and psychotic behavior have been noted, particularly in adults and there are a range of classic medications that have been administered.…”

Section: Alström Syndrome Clinical Overviewmentioning

confidence: 99%

Alstrom Syndrome: Genetics and Clinical Overview

Marshall

Maffei²,

Collin³

et al. 2011

231

298

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Alström syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background.Alström syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet-Biedl syndrome.Studies involving murine and cellular models of Alström syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alström syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population.

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Alström Syndrome Associated With Cerebral Involvement: An Unusual Presentation

Cited by 5 publications

References 7 publications

Brain involvement in Alström syndrome

Brain involvement in Alström syndrome

Theory-of-mind in individuals with Alström syndrome is related to executive functions, and verbal ability

Alstrom Syndrome: Genetics and Clinical Overview

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