scholarly journals INPP5K-Related congenital muscular dystrophy: when juvenile cataracts give clues to a complex diagnosis

2021 ◽  
Author(s):  
Roberta Ismael Lacerda Machado ◽  
Bruno de Mattos Lombardi Badia ◽  
Wladimir Bocca Vieira de Rezende Pinto ◽  
Igor Braga Farias ◽  
José Marcos Vieira de Albuquerque Filho ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Intellectual Disability ◽  
Genetic Testing ◽  
Motor Development ◽  
Brain Mri ◽  
Congenital Muscular Dystrophy ◽  
The Elderly ◽  
Adult Brain ◽  
Mild Intellectual Disability ◽  
Leg Weakness

Introduction: Congenital muscular dystrophies (CMDs) are a group of rare genetic muscle diseases that present at birth or during infancy with hypotonia and weakness. Multiple forms of CMDs are also associated with cerebral and ocular phenotypes. Recently, INPP5K mutations have been described associated with CMD, cataracts and cognitive impairment. The INPP5K gene, encodes SKIP, one of the enzymes that phosphorylate the 5-phosphate position of phosphoinositides and is highly expressed in developing and adult brain, eye and muscle. Methods: We performed a case report of three Brazilian patients with INPP5KCMD with cataracts and intellectual disability under clinical follow-up at our service. Results: Case 1: 39 years old, female, presenting with progressive leg weakness since childhood, mild intellectual disability and bilateral cataracts at 20 years. Her 35-yearold sister (Case 2) had a similar clinical picture with limb-girdle weakness since childhood, cognitive impairment and early- onset bilateral cataracts. Both with myopathic pattern in EMG, elevated creatine phosphokinase (CK) and dystrophic pattern in muscle biopsy. Brain MRI studies disclosed a large megacistern in the elderly and no abnormalities in the younger sister. Genetic testing: c.653_655del(p.(Ser218del) in homozygosity in INPP5K gene. Case 3: 20 years old, female, normal motor development but learning difficulties since childhood. Presented with progressive pelvic girdle weakness in childhood and bilateral cataracts in late adolescence. Exams disclosed elevated CK, brain MRI was normal and genetic testing with the following mutation in INPP5K gene:c.[881_883del];[1088T>C];p.[Ser294del];[Ile363Thr]. Conclusion: We describe patients with CMD, cataracts and intellectual disability, caused by mutation in the INPP5K gene. In literature few cases are reported.

scholarly journals SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum

2021 ◽  
pp. jmedgenet-2021-108114
Author(s):  
Valentina Serpieri ◽  
Fulvio D’Abrusco ◽  
Jennifer C Dempsey ◽  
Yong-Han Hank Cheng ◽  
Filippo Arrigoni ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Testing ◽  
Splice Site ◽  
De Novo ◽  
Diagnostic Yield ◽  
Brain Mri ◽  
Recurrence Risk ◽  
Joubert Syndrome ◽  
Medical Monitoring ◽  
Motor Apraxia

BackgroundJoubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%.In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies.MethodsWe reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes.ResultsHeterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents.ConclusionHeterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk.

scholarly journals Is Brain MRI Needed in Diagnostic Evaluation of Mild Intellectual Disability?

2020 ◽  
Author(s):  
Miro Pekka Jussila ◽  
Päivi Olsén ◽  
Jaakko Niinimäki ◽  
Maria Suo-Palosaari
Keyword(s):  
Intellectual Disability ◽  
Clinical Symptoms ◽  
Brain Mri ◽  
Neurological Symptoms ◽  
Diagnostic Evaluation ◽  
Mild Intellectual Disability ◽  
Mri Findings ◽  
Patient Reports ◽  
Epilepsy Diagnosis ◽  
Abnormal Head

Abstract Aim The purpose of our study was to suggest an imaging strategy and guidelines for the selection of the children with mild intellectual disability (ID) for magnetic resonance imaging (MRI), to avoid unnecessary imaging. Methods The brain MRIs and patient reports of 471 children were reviewed for the imaging findings and ID severity. The correlation between the clinical and brain MRI findings was analyzed in the 305 children with mild ID. Results Thirty-eight (12.5%) of the children with mild ID had significant abnormal brain MRI findings. Thirty-five of these had other neurological symptoms or diseases in addition to ID, which were an indication for brain MRI. In the logistic regression analysis, seizures (in patients without an epilepsy diagnosis), epilepsy, movement disorders, dysmorphia, encephalitis, traumatic brain injury, and abnormal head size were statistically significant symptoms or comorbidities associated with abnormal MRI findings. Only three children (1.0%) with mild ID had a significant MRI finding without any other clinical symptoms or disease. Conclusion Routine MRI in children with mild ID without specific neurological symptoms, dysmorphic features, or related diseases is not suggested for revealing an etiology of mild ID. Since children with ID usually need to be sedated for MRI, routine imaging in the diagnostic evaluation of mild ID should be carefully considered. Clinical examination, other symptoms, and related diseases should be carefully assessed to decide the need for MRI.

scholarly journals Peculiarities of Psychomotor Reaction of Schoolchildren with Intellectual Disabilities: Aspects of Moderate Intensity Exercising and Age

2018 ◽  
Vol 3 (94) ◽  
Author(s):  
Dovilė Selickaitė ◽  
Diana Rėklaitienė ◽  
Jūratė Požėrienė
Keyword(s):  
Heart Rate ◽  
Intellectual Disability ◽  
Reaction Time ◽  
Motor Development ◽  
Independent Living ◽  
Positive Influence ◽  
Moderate Intensity ◽  
Mild Intellectual Disability ◽  
Complex Information ◽  
Before And After

Background. Intellectual disability is defined as significantly reduced ability to understand new or complex information, to learn and to apply new skills. Integration into the society and independent living for intellectually disabled people is demanding because of slowdown decision processing. Quick enough response time is of vital importance not only for the motor development but also for faster and better adaptation to the changing life conditions.  Methods. The  subjects  were  112  persons  with  and  without  intellectual  disability  aged  11  to  18  years  and recruited for the study. The Reaction Timer RA-1 was used to measure reaction time and to determine the speed characteristics  of  the  person’s  psychomotor  response  before  and  after  moderate  intensity  exercising.  Heart  rate monitor Polar RS800 was used to measure the person’s heart rate. Results. The best reaction time was demonstrated by 16-year-old normally developed individuals and those with mild intellectual disability (p < .05). The slowest were 11 and 12-year-old individuals (p < .05). The best reaction time was demonstrated by 14-year-old individuals with moderate intellectual disability and the worst – by 12 and 16 year-old persons with this disability (p < .05).Conclusion. Moderate-intensity exercising has a positive influence on the execution of the complex reaction task (LRHL). The considerable reaction time increase was observed for individuals with moderate intellectual disability.Keywords: intellectual disability, reaction time, moderate intensity exercising.

scholarly journals Evaluating fine perceptual-motor skills in children with mild intellectual disability

2021 ◽  
Vol 3 (1) ◽  
pp. 97-108
Author(s):  
Vasiliki Koutsobina ◽  
◽  
Victoria Zakopoulou ◽  
Eftychia Tziaka ◽  
Vasilios Koutras ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Motor Skills ◽  
Motor Development ◽  
Assessment Tool ◽  
Typically Developing ◽  
Mild Intellectual Disability ◽  
Typically Developing Children ◽  
Mental Age ◽  
And Performance ◽  
Perceptual Motor Skills

Over the years, several studies have indicated that delay in perceptual-motor development and impaired motor organization is strongly associated with the level of cognitive functioning and performance in children. The aim of the present research study was to assess the fine perceptual-motor skills of children with mild intellectual disability 7-9-years-old and the comparison of their performance with two groups of typically developing children with the same chronological and a corresponding mental age. Our research sample consisted of 129 children between the ages of four and nine years whilst the experimental group had a total of 43 children (7-9-years-old) with mild intellectual disability. As an assessment tool of fine perceptual-motor skills we used a battery of tasks constructed in accordance with other commonly used standardized tests that measure psychomotor abilities. Furthermore, several comparisons were carried out in order to investigate our experimental hypotheses. Overall, our results revealed that children with mild intellectual disability scored lower in the tasks compared to typically developing children of equal chronological age but significantly higher than the group of typically developing children of the same mental age (preschoolers). The results of the psychometric properties of our designed tasks (reliability, validity) verify the high-quality psychometric characteristics of the designed tool.

scholarly journals Normal pressure hydrocephalus

2021 ◽  
Vol 13 ◽  
pp. e017
Author(s):  
Maria Eduarda Turczyn De Lucca ◽  
Leonardo Cesar Ferreira Antunes ◽  
Carlos Arteaga Rodriguez ◽  
Otto Jesus Hernández Fustes
Keyword(s):  
Urinary Incontinence ◽  
Cognitive Impairment ◽  
Normal Pressure Hydrocephalus ◽  
Randomized Clinical Trials ◽  
Brain Mri ◽  
Normal Pressure ◽  
The Elderly ◽  
Advanced Stages ◽  
Clinical Tools ◽  
Rule Out

Normal pressure hydrocephalus – NPH is one of the potentially reversible causes of dementia. In this work, we provide the clinical tools for the management of NPH to the Primary Health Care – PHC physicians. The PubMed and Cochrane databases were reviewed, and 40 articles were chosen, which include randomized clinical trials, metanalysis and systematic reviews. The symptoms of the classic triad are nonspecific and found in the elderly with other diseases. Gait apraxia is the earliest symptom, followed by cognitive impairment and urinary incontinence. The concomitance of the three symptoms occurs in about 60% of the cases in the advanced stages. Apraxia of gait is presented with short steps, without sensorial, vestibulocerebellar or muscle strength changes, which allows it to be distinguished from other pathological marches. Cognitive impairment is subcortical – psychomotor slowliness, inattention, loss of working memory and executive function and preservation of episodic memory – unlike cortical dementias, such as Alzheimer's disease. Urinary incontinence must be distinguished from overflow by prostatism and stress incontinence in women. The PHC physician, when faced with the triad, should request a CT scan or brain MRI and, in the presence of one or two symptoms, rule out other diagnoses. Patients with NPH seek help from the physician in the PHC who must know how to identify and differentiate their symptoms. In the case of suspicion, the study of neuroimaging is mandatory and referral to neurosurgery or neurology is recommended.

Easy Screening for Mild Alzheimer's Disease and Mild Cognitive Impairment from Elderly Speech

2018 ◽  
Vol 15 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Shohei Kato ◽  
Akira Homma ◽  
Takuto Sakuma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Characteristic Curve ◽  
Linear Regression Analysis ◽  
Speech Sound ◽  
The Elderly ◽  
Speech Sounds ◽  
Mel Frequency Cepstral Coefficients

Objective: This study presents a novel approach for early detection of cognitive impairment in the elderly. The approach incorporates the use of speech sound analysis, multivariate statistics, and data-mining techniques. We have developed a speech prosody-based cognitive impairment rating (SPCIR) that can distinguish between cognitively normal controls and elderly people with mild Alzheimer's disease (mAD) or mild cognitive impairment (MCI) using prosodic signals extracted from elderly speech while administering a questionnaire. Two hundred and seventy-three Japanese subjects (73 males and 200 females between the ages of 65 and 96) participated in this study. The authors collected speech sounds from segments of dialogue during a revised Hasegawa's dementia scale (HDS-R) examination and talking about topics related to hometown, childhood, and school. The segments correspond to speech sounds from answers to questions regarding birthdate (T1), the name of the subject's elementary school (T2), time orientation (Q2), and repetition of three-digit numbers backward (Q6). As many prosodic features as possible were extracted from each of the speech sounds, including fundamental frequency, formant, and intensity features and mel-frequency cepstral coefficients. They were refined using principal component analysis and/or feature selection. The authors calculated an SPCIR using multiple linear regression analysis. Conclusion: In addition, this study proposes a binary discrimination model of SPCIR using multivariate logistic regression and model selection with receiver operating characteristic curve analysis and reports on the sensitivity and specificity of SPCIR for diagnosis (control vs. MCI/mAD). The study also reports discriminative performances well, thereby suggesting that the proposed approach might be an effective tool for screening the elderly for mAD and MCI.

Post-stroke Cognitive Impairment and Malnutrition in the Elderly (PCIME): study design and protocol

2021 ◽  
Author(s):  
Zahra Vahabi ◽  
M. Reza Azarpazhooh ◽  
Shima Raeesi ◽  
Shahram Oveisgharan ◽  
Farnaz Etesam ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Study Design ◽  
The Elderly ◽  
Post Stroke

scholarly journals Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

2021 ◽  
Author(s):  
Meena Balasubramanian ◽  
Alexander J. M. Dingemans ◽  
Shadi Albaba ◽  
Ruth Richardson ◽  
Thabo M. Yates ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Protein Function ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Mild Intellectual Disability ◽  
Related Disorder ◽  
Feeding Difficulties ◽  
Facial Phenotype ◽  
Novel Variants ◽  
Common Behaviour

AbstractWitteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12.

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