Intellectual disability may present as the sole clinical feature (non-syndromic), or may be present with additional clinical or dysmorphological features (syndromic). [google.la]

Clinical presentation The patient group ( Table 2 ) showed a predominant neurological presentation with a wide range of mild to severe global developmental delay in all 12 patients. Intellectual disability was present in all patients 5 years. [brain.oxfordjournals.org]

(Wednesday, May 29th 3:30-5:30 pm) ClinGen Posters and Presentations - ACMG 2019 Gene Disease Validity General Training Presentation Updated February 2018. [clinicalgenome.org]

[…] in the score cards) could also boost a gene from category 4 to 3. 1/1/2017 Description Homozygous loss-of-variant (LoF) variants in the CC2D1A gene were identified in four families with a total of 16 individuals affected with a variable spectrum of presentations [gene.sfari.org]

We report a consanguineous Omani family in which multiple individuals have ID and developmental delay together with some variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the [eprints.whiterose.ac.uk]

• Disability

  disability (ID) is one of the most demanding challenges for clinical Geneticists and Researchers. [moh-it.pure.elsevier.com]

  (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score 3.7). [pdfs.semanticscholar.org]

  X-linked intellectual disability accounts for 16% of all cases of intellectual disability in males. [ipscenter.nl]

  […] and cause up to 50% of intellectual disability worldwide. [medicalxpress.com]

• Camping

  […] behavioural or neurodevelopmental disorders Neurodevelopmental disorders 6A00 Disorders of intellectual development H00773 Autosomal dominant mental retardation Pathway hsa04728 Dopaminergic synapse hsa04261 Adrenergic signaling in cardiomyocytes hsa04024 cAMP [kegg.jp]

  Smith RHJ, Shearer AE, Hildebrand MS, Van Camp G. Deafness and hereditary hearing loss overview. GeneReviews [Internet]. RA Pagon, MP Adam, HH Ardinger, et al., eds. Seattle, WA: University of Washington, Seattle; updated January 9, 2014. [aetna.com]

• Asymptomatic

  Pulmonary AVMs (PAVMs) can be asymptomatic or manifest as dyspnea and hypoxemia secondary to shunting. [aetna.com]

  DNA analysis of asymptomatic patients with a positive family history of an autosomal dominant ataxia is also possible. Predictive testing of these patients, including prenatal diagnosis, introduces complex issues and risks. [chginc.org]

• Dysphagia

  ALS patients with C9orf72 expansions are more likely to have Parkinsonism and bulbar findings (dysphagia, dysarthria). Some individuals with repeat expansions in C9orf72 also develop frontotemporal dementia (FTD). [chginc.org]

  Affected individuals typically present with asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia). [aetna.com]

• Prognathism

  […] syndrome Genetic condition characterized by the core phenotype of developmental delay, intellectual disability, speech impairment, (childhood) hypotonia and distinct facial features, including synophrys, hypertelorism, midface hypoplasia, anteverted nares, prognathism [nature.com]

• Strabismus

  […] defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. ( 17847003 ) Motazacker M.M....Kuss A.W. 2007 14 Autosomal recessive mental retardation syndrome with anterior maxillary protrusion and strabismus [malacards.org]

  In Family 4, Patient 4.1 shows features that are commonly present in other types of CDGs, including hypotonia, strabismus and inverted nipples, whereas the other sibling has a syndromal intellectual disability phenotype with macrocephaly, aggressivity [brain.oxfordjournals.org]

  Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus Alazami, A. M.; Hijazi, H.; Al‐Dosari, M. S.; Shaheen, R.; Hashem, A.; Aldahmesh, M. A. [deepdyve.com]

  No facial dysmorphism was observed except for affected individual IV-10 who had strabismus (Figure 2 ). [bmcmedgenet.biomedcentral.com]

  Alazami AM, Hijazi H, Al-Dosari MS, Shaheen R, Hashem A, Aldahmesh MA, Mohamed JY, Kentab A, Salih MA, Awaji A, Masoodi TA, Alkuraya FS Title Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus [genome.jp]

• Aniridia

  cerebellar ataxia - intellectual deficit Autosomal dominant keratitis Extraskeletal Ewing sarcoma Foveal hypoplasia - presenile cataract Isolated aniridia Isolated optic nerve hypoplasia Morning glory syndrome Peters anomaly WAGR syndrome Williams [csbg.cnb.csic.es]

  […] in children and adolescents with obsessive–compulsive disorder Hauser et al. 2006 Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma Grønskov et al. 2001 Population-based risk estimates of Wilms tumor in sporadic aniridia [google.la]

• Fracture

  […] early-onset osteoarthritis Multiple epiphyseal dysplasia, Beighton type Platyspondylic dysplasia, Torrance type Spondyloepimetaphyseal dysplasia congenita, Strudwick type Spondyloepiphyseal dysplasia congenita Spondylometaphyseal dysplasia, 'corner fracture [csbg.cnb.csic.es]

  To date, there are no genome-wide association studies on fracture or BMD loss. Therefore, it remains unclear whether the same genes that determine BMD also affect the rate of bone loss with advancing age or the risk of fractures”. [aetna.com]

  IMPERFECTA TYPE I, II, III, IV GENES: COL1A1 (collagen, type I, alpha 1); COL1A2 (collagen, type I, alpha 2) CHROMOSOMAL LOCATION: 17q21.33 (COL1A1), 7q22.1 (COL1A2) MODE OF INHERITANCE: Autosomal dominant Osteogenesis imperfecta (OI) is characterized by fractures [chginc.org]

• Arthritis

  […] connective tissue disorder that includes ophthalmologic (myopia, cataract, and retinal detachment), craniofacial (Pierre Robin sequence: micrognathia, glossoptosis, cleft palate, midface hypoplasia), audiologic (hearing loss), and joint abnormalities (early arthritis [chginc.org]

  Hereditary Hemochromatosis Hemochromatosis, a condition involving excess accumulation of iron, can lead to iron overload, which in turn can result in complications such as cirrhosis, diabetes, cardiomyopathy, and arthritis (Burke 1992; Hanson et al, 2001 [aetna.com]

• Muscle Spasticity

  Common features of XLAG include muscle spasticity, hypotonia, epilepsy, abnormal genitalia, developmental delay, and severe intellectual disability. [chginc.org]

• Ankylosis

  2 Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel. ( 21643797 ) Rehman S.u....Hansen L. 2011 3 Autosomal recessive mental retardation, deafness, ankylosis [malacards.org]

• Papule

  Affected individuals have macrocephaly and almost all will develop mucocutaneous lesions including trichilemmomas, papillomatous papules, and acral and plantar keratoses. [chginc.org]

• Dermatitis

  […] of disease transmission to offspring Melville et al. 2005 A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs Fölster-Holst et al. 1998 Linkage between atopy and the IgE high-affinity receptor gene at 11q13 in atopic dermatitis [google.la]

• Fear

  Contextual fear conditioning showed a significant decrease in the percentage of freezing time in CamKII(cre/ ), crbn(-/-) and crbn(-/-) mice while motor function, exploratory motivation, and anxiety-related behaviors were normal. [ncbi.nlm.nih.gov]

• Anxiety Disorder

  It is formed of a 97-item questionnaire covering eight domains, namely, anxiety disorder, depressive episode, manic episode, obsessive compulsive disorder, psychosis, attention-deficit hyperkinetic disorder, conduct disorder and autism spectrum disorder [dovepress.com]

• Neonate-Onset

  FHI can manifest as early as within a few hours after birth (neonatal-onset) or in the first months of life (childhood-onset). [chginc.org]

  A, Hopkin RJ, Dubbs HA, Ortiz-Gonzalez XR, Pfundt R, Brunner HG, Fisher SE, Kleefstra T and Cooper GM Human genetics 2018 PUBMED: 29740699 ; PMC: 5973976 ; DOI: 10.1007/s00439-018-1887-y A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset [ddduk.org]

• Nystagmus

  Eye examination showed alternating esotropia and fine horizontal nystagmus, fundus examination could not be done. The rest of her cranial nerve examination was grossly normal. [google.la]

  X-linked congenital stationary night blindness with myopia and nystagmus without clinical complaints of nyctalopia. J Pediatr Ophthalmol Strabismus. 1988;25(1):33-36. Lorenz B, Andrassi M, Miliczek KD. [aetna.com]

  Part A 2016 ; 170 ; 6 ; PUBMED: 26940150 ; DOI: 10.1002/ajmg.a.37604 Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity. [ddduk.org]

  The condition typically presents in infancy or early childhood and is characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity. [chginc.org]

• Myoclonus

  De Fusco M, Vago R, Striano P, et al. (2014) The alpha2B‐adrenergic receptor is mutant in cortical myoclonus and epilepsy. Annals of Neurology 75 (1): 77–87. [els.net]

  SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain. Neurology 75, 1454–1458 (2010). 88. McCarthy, S. E. et al. [nature.com]

  Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder characterized by myoclonus, seizures, ataxia, choreoathetosis and dementia. [chginc.org]

  Epsilon-Sarcoglycan Gene (SCGE) Deletion Analysis Myoclonus-dystonia (M-D), an autosomal dominant inherited movement disorder, has been associated with mutations in the epsilon-sarcoglycan gene (SCGE) on 7q21. [aetna.com]

• Febrile Seizures

  creatine transporter 1 sequencing for testing parents of individuals with seizures; GABRG2 mutations for infantile febrile seizures; Generalized epilepsy with febrile seizures plus (GEFS )) Sleep-walking Townes-Brocks syndrome (SALL1 gene) Type 2 diabetes [aetna.com]

  Variants in this gene are associated with a range of phenotypes that include generalized epilepsy with febrile seizures, early infantile epileptic encephalopathy, Dravet syndrome and intractable childhood epilepsy, severe myoclonic epilepsy of infancy [chginc.org]

Recently, Cooper and colleagues 82 looked at data from 15,767 patients who had undergone array CGH analysis as part of the diagnostic workup. [nejm.org]

History of admission to neonatal intensive care unit was significantly higher among the patient group than among the controls ( P Conclusion: Metabolic testing should be considered in the workup of individuals with nonsyndromic ID, which will need further [dovepress.com]

Thus, SYCP3 testing may be considered in the workup for women with recurrent pregnancy loss, and in males with non-obstructive azoospermia. Our laboratory offers DNA sequencing of all coding exons (2-9) of the SYCP3 gene. [chginc.org]

[…] trio approach using next generation sequencing could explain a consistent percentage of patients with isolated ID, thus increasing our knowledge on the molecular bases of this disease and opening new perspectives for a better diagnosis, counseling, and treatment [moh-it.pure.elsevier.com]

It also helps in initiating the treatment in the earlier stages of development as it will be more effective and will improve the outcome at a later stage. [dovepress.com]

Treatment of mitochondrial disorders is largely supportive. [aetna.com]

By treatment with neuraminidase ( n), a single band is observed for MAN1B1-CDG, whereas a polymorphism is indicated by two bands after treatment with neuraminidase. ( C ) Schematic presentation of the MAN1B1 protein, indicating the cytosolic (Cyt), transmembrane [brain.oxfordjournals.org]

The presence of syndactyly seems to represent a different genetic variant of LQTS also associated with a poor prognosis. [aetna.com]

Patients have increased LDL values from birth, and an increased cardiovascular risk, making early diagnosis and treatment imperative for improved prognosis. Three main causative genes have been associated with FH: LDLR, APOB and PCSK9. [clinicalgenome.org]

In this Review, we highlight the insights obtained from recent studies on the role of genetics in ID and its impact on diagnosis, prognosis and therapy. [nature.com]

As the data continue to accumulate, our understanding of genes, pathways, and molecular mechanisms will continue to evolve and translate into better diagnosis, prognosis, and therapies for these severe disorders. [nejm.org]

The etiology remains unknown in up to 80% of cases with mild intellectual disability (4). Depending on the underlying etiology, the recurrence risk can vary between the background and 50%. [dnatesting.uchicago.edu]

Despite multiples genes involved in the etiology of disease, most of the genetic background is yet to be discovered. [sparrho.com]

It is estimated that mutations in the genes on the X chromosome may account for about 10% of all cases of ID, thus molecular investigations into the X chromosome in elucidating the etiology of an individual with ID have been routinely suggested. [ashg.org]

Mental retardation and multiple congenital anomalies of unknown etiology: frequency of occurrence in similarly affected sibs of the proband. Birth Defects Orig Artic Ser 1978; 14: 127-37. 8. [jpma.org.pk]

Mental retardation and multiple congenital anomalies of unknown etiology: frequency of occurrence in similarly affected sibs of the proband. Birth Defects Orig Artic Ser 1978 ; 14 : 127 – 137. 11. Hussain, R, Bittles, AH. [cambridge.org]

Author information 1 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK. 2 Centre for Integrated Genomic Medical Research, University of Manchester [ncbi.nlm.nih.gov]

Relevant External Links for CC2D1A Genetic Association Database (GAD) CC2D1A Human Genome Epidemiology (HuGE) Navigator CC2D1A Atlas of Genetics and Cytogenetics in Oncology and Haematology: CC2D1A No data available for Genatlas for CC2D1A Gene The CC2D1A [genecards.org]

The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment. Retard. Dev. Disabil. Res. Rev. 8, 117–134 (2002). 22. Lubs, H. A., Stevenson, R. E. & Schwartz, C. E. [nature.com]

An epidemiological/genetic study of mental subnormality in Assiut Governorate, Egypt. Clin Genet. 1994;46(5):347–351. 20. Wasant P, Vatanavicharn N, Srisomsap C, Sawangareetrakul P, Liammongkolkul S, Svasti J. [dovepress.com]

The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment Retard Dev Disabil Res Rev 2002; 8: 117-34. 2. Diagnostic and statistical manual of mental disorders. Text revision (DSM-IV-TR). 4th ed. [jpma.org.pk]

Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis, Biol Chem., 2009, 390, 591-599. PubMed Google Scholar [58] Rafiq M. A., Kuss A. [degruyter.com]

Clinical manifestations, pathophysiology, and diagnosis of atrioventricular (AV) canal defects. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2013. Altman CA. [aetna.com]

Vincent's team aims to provide scientists more clues to understand, diagnose, prevent, and treat intellectual disabilities. [eurekalert.org]

In some cases (eg, phenylketonuria [PKU] and hypothyroidism), retardation is preventable with early treatment. Other disorders (eg, mucopolysaccharidosis and sphingolipidoses) are less responsive to early intervention. [dovepress.com]

Common (but preventable) environmental causes of ID are iodine deficiency and malnutrition (of both mother and child), affecting millions of people in “developing countries”. [f1000research.com]

While pharmacotherapies have made some impact on the prevention of SCD, the introduction of implantable cardioverter-defibrillator (ICD) therapy has been the single major advance in the prevention of SCD in the young. [aetna.com]

Clinical Actionability Tools Clinical Actionability tools support the curation process is to identify those human genes that, when significantly altered, confer a high risk of serious disease that could be prevented or mitigated if the risk were known [clinicalgenome.org]