Innovations in the Early Diagnosis of Chromosomal Disorders Associated with Intellectual Disability

Background: Intellectual disability (ID) is a neuro-developmental defect that is manifested by development delay and learning disability. Such defects may be caused due to chromosomal disorders (trisomy 18 or Down syndrome) or single gene mutation. Its worldwide prevalence is estimated to be 1-3%. The genetic etiology of non-syndromic ID is poorly understood. To date, more than 100 loci have been reported to be associated with non-syndromic ID. The objective of this study was to identify the causative genes for three Materials & Methods: This cross-sectional study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan from March 2014 to August 2015. The inclusion criteria set for the families was consanguineous relation and more than two patients per family (including cousins). All the patients were tested individually in friendly atmosphere using IQ test to scale the ID on the basis of performance. Thereafter, blood samples were taken by aseptic method and DNA was extracted for the purpose of doing genetic analysis. In genetic analysis, exome sequencing was performed to find the pathogenic variants. Subsequently. Sanger sequencing was also done to see the segregation of pathogenic variants. Results: Genetic analysis found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. Conclusion: The study involved genetic analysis of three consanguineous families and found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. The present research will help in devising molecular diagnostic technics for pre-marital and pre-conception testing.

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Pitt-Hopkins Syndrome: Clinical and Molecular Findings of a 5-Year-Old Patient

Genes ◽

10.3390/genes11060596 ◽

2020 ◽

Vol 11 (6) ◽

pp. 596

Author(s):

Florin Tripon ◽

Alina Bogliș ◽

Cristian Micheu ◽

Ioana Streață ◽

Claudia Bănescu

Keyword(s):

Intellectual Disability ◽

Early Diagnosis ◽

Rare Condition ◽

Mild Intellectual Disability ◽

Nasal Bridge ◽

Craniofacial Dysmorphism ◽

Wide Mouth ◽

Exon 9 ◽

Exon 20 ◽

Short Philtrum

Pitt Hopkins syndrome (PTHS) is a very rare condition and until now, approximately 500 patients were reported worldwide, of which not all are genetically confirmed. Usually, individuals with variants affecting exons 1 to 5 in the TCF4 gene associate mild intellectual disability (ID), between exons 5 to 8, moderate to severe ID and sometimes have some of the characteristics of PTHS, and variants starting from exon 9 to exon 20 associate a typical PTHS phenotype. In this report, we describe the clinical and molecular findings of a Caucasian boy diagnosed with PTHS. PTHS phenotype is described including craniofacial dysmorphism with brachycephaly, biparietal narrowing, wide nasal bridge, thin and linear lateral eyebrows, palpebral edema, full cheeks, short philtrum, wide mouth with prominent and everted lips, prominent Cupid’s bow, downturned corners of the mouth, microdontia and also the clinical management of the patient. The previously and the current diagnosis scores are described in this report and also the challenges and their benefits for an accurate and early diagnosis.

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GENETIC ANALYSIS OF FAMILIES HAVING AUTOSOMAL RECESSIVE INTELLECTUAL DISABILITY

Gomal Journal of Medical Sciences ◽

10.46903/gjms/17.02.1908 ◽

2019 ◽

Vol 17 (2) ◽

pp. 42-46 ◽

Cited By ~ 1

Author(s):

Jamshed Khan ◽

Muhammad Junaid ◽

Shahab Uddin ◽

Khalida Moeed ◽

Usman Ullah ◽

...

Keyword(s):

Intellectual Disability ◽

Genetic Analysis ◽

Single Gene ◽

Cross Sectional Study ◽

Molecular Diagnostic ◽

Developmental Defect ◽

Chromosomal Disorders ◽

Cross Sectional ◽

Pathogenic Variants ◽

Development Delay

Background: Intellectual disability (ID) is a neuro-developmental defect that is manifested by development delay and learning disability. Such defects may be caused due to chromosomal disorders (trisomy 18 or Down syndrome) or single gene mutation. Its worldwide prevalence is estimated to be 1-3%. The genetic etiology of non-syndromic ID is poorly understood. To date, more than 100 loci have been reported to be associated with non-syndromic ID. The objective of this study was to identify the causative genes for three Materials & Methods: This cross-sectional study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan from March 2014 to August 2015. The inclusion criteria set for the families was consanguineous relation and more than two patients per family (including cousins). All the patients were tested individually in friendly atmosphere using IQ test to scale the ID on the basis of performance. Thereafter, blood samples were taken by aseptic method and DNA was extracted for the purpose of doing genetic analysis. In genetic analysis, exome sequencing was performed to find the pathogenic variants. Subsequently. Sanger sequencing was also done to see the segregation of pathogenic variants. Results: Genetic analysis found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. Conclusion: The study involved genetic analysis of three consanguineous families and found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. The present research will help in devising molecular diagnostic technics for pre-marital and pre-conception testing.

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Intellectual Disability—Concepts, Aetiology, and Genetics

Oxford Textbook of the Psychiatry of Intellectual Disability ◽

10.1093/med/9780198794585.003.0003 ◽

2020 ◽

pp. 23-34

Author(s):

Satish C. Girimaji ◽

Salah Basheer ◽

Asit Biswas ◽

Satheesh Kumar Gangadharan

Keyword(s):

Intellectual Disability ◽

Copy Number ◽

Adaptive Functioning ◽

Medical Condition ◽

Single Gene ◽

Neurodevelopmental Disorder ◽

Copy Number Variations ◽

Chromosomal Disorders ◽

Single Gene Disorders ◽

Cultural Construct

There are three major conceptualizations of Intellectual Disability (ID): as a lower end of the Gaussian distribution of intelligence in the population, a bio-medical condition secondary to adverse influences on the developing brain (neurodevelopmental disorder), and as a socio-cultural construct focusing on impairments in adaptive functioning and the need for extra supports. Modern definitions incorporate all these aspects. There are hundreds of causes of ID, both genetic and environmental, that act either singly or in combination. These are classified based on the timing (pre-, peri-, and postnatal) and the type of cause. Genetic factors include chromosomal disorders, microdeletions, single gene disorders and newly discovered mechanisms such as copy number variations. Environmental factors may operate in prenatal, perinatal, or postnatal periods of development. Pathophysiological pathways leading to ID involve disruption of neurodevelopment and neuronal functioning, such as neural proliferation, migration, connectivity, synaptic development, intra- and inter-cellular signalling pathways, and metabolism. Identifying the aetiology has major clinical implications.

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Speech and language profiles in 4- to 6-year-old children with early diagnosis of autism spectrum disorder without intellectual disability

Neuropsychiatric Disease and Treatment ◽

10.2147/ndt.s171971 ◽

2018 ◽

Vol Volume 14 ◽

pp. 2415-2427 ◽

Cited By ~ 5

Author(s):

Liselotte Kjellmer ◽

Elisabeth Fernell ◽

Christopher Gillberg ◽

Fritjof Norrelgen

Keyword(s):

Autism Spectrum Disorder ◽

Intellectual Disability ◽

Early Diagnosis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Speech And Language ◽

Language Profiles

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Normocentric biases taint cognitive neuroscience and intervention of autism

Behavioral and Brain Sciences ◽

10.1017/s0140525x18002297 ◽

2019 ◽

Vol 42 ◽

Cited By ~ 1

Author(s):

Laurent Mottron

Keyword(s):

Intellectual Disability ◽

Cognitive Neuroscience ◽

Social Motivation ◽

Repetitive Behaviors ◽

Restricted Interests ◽

Autistic People

Abstract Stepping away from a normocentric understanding of autism goes beyond questioning the supposed lack of social motivation of autistic people. It evokes subversion of the prevalence of intellectual disability even in non-verbal autism. It also challenges the perceived purposelessness of some restricted interests and repetitive behaviors, and instead interprets them as legitimate exploratory and learning-associated manifestations.

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Red Flags: Barriers to Listening and Spoken Language in Children with Hearing Loss

Perspectives on Hearing and Hearing Disorders in Childhood ◽

10.1044/hhdc24.1.11 ◽

2014 ◽

Vol 24 (1) ◽

pp. 11-18

Author(s):

Andrea Bell ◽

K. Todd Houston

Keyword(s):

Hearing Loss ◽

Early Diagnosis ◽

Skill Acquisition ◽

Dynamic Process ◽

Spoken Language ◽

Red Flags ◽

Careful Monitoring ◽

Auditory Development ◽

Children With Hearing Loss ◽

Family Centered

To ensure optimal auditory development for the acquisition of spoken language, children with hearing loss require early diagnosis, effective ongoing audiological management, well fit and maintained hearing technology, and appropriate family-centered early intervention. When these elements are in place, children with hearing loss can achieve developmental and communicative outcomes that are comparable to their hearing peers. However, for these outcomes to occur, clinicians—early interventionists, speech-language pathologists, and pediatric audiologists—must participate in a dynamic process that requires careful monitoring of countless variables that could impact the child's skill acquisition. This paper addresses some of these variables or “red flags,” which often are indicators of both minor and major issues that clinicians may encounter when delivering services to young children with hearing loss and their families.

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