The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders
Abstract
:1. Introduction
2. Autism and Ehlers-Danlos Syndrome Comorbidity and Familial Co-Occurrence
3. The Genetics of Hypermobility
4. Symptom Overlap between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders
4.1. The Nervous System
4.1.1. Neurobehavioral, Psychiatric, and Neurological Features
4.1.2. Coordination Problems and Sensory Issues
4.1.3. Autonomic Dysregulation
4.2. Immune Dysregulation
5. Conclusions
Precision Medicine and HCTD in Autism
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Weiner, D.J.; Wigdor, E.M.; Ripke, S.; Walters, R.K.; Kosmicki, J.A.; Grove, J.; Samocha, K.E.; Goldstein, J.I.; Okbay, A.; Bybjerg-Grauholm, J.; et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat. Genet. 2017, 49, 978–985. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klei, L.; Sanders, S.J.; Murtha, M.T.; Hus, V.; Lowe, J.K.; Willsey, A.J.; Moreno-De-Luca, D.; Timothy, W.Y.; Fombonne, E.; Geschwind, D.; et al. Common genetic variants, acting additively, are a major source of risk for autism. Mol. Autism 2012, 3, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herbert, M.R. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr. Opin. Neurol. 2010, 23, 103–110. [Google Scholar] [CrossRef] [PubMed]
- Tordjman, S.; Somogyi, E.; Coulon, N.; Kermarrec, S.; Cohen, D.; Bronsard, G.; Bonnot, O.; Weismann-Arcache, C.; Botbol, M.; Lauth, B.; et al. Gene x environment interactions in autism spectrum disorders: Role of epigenetic mechanisms. Front. Psychiatry 2014, 5, 53. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stein, J.L.; Parikshak, N.N.; Geschwind, D.H. Rare inherited variation in autism: Beginning to see the forest and a few trees. Neuron 2013, 77, 209–211. [Google Scholar] [CrossRef] [Green Version]
- Casanova, E.L.; Gerstner, Z.; Sharp, J.L.; Casanova, M.F.; Feltus, F.A. Widespread genotype-phenotype correlations in intellectual disability. Front. Psychiatry 2018, 9, 535. [Google Scholar] [CrossRef] [Green Version]
- Oliver, C.; Berg, K.; Moss, J.; Arron, K.; Burbidge, C. Delineation of behavioral phenotypes in genetic syndromes: Characteristics of autism spectrum disorder, affect and hyperactivity. J. Autism Dev. Disord. 2011, 41, 1019–1032. [Google Scholar] [CrossRef]
- Héron, B.; Mikaeloff, Y.; Froissart, R.; Caridade, G.; Maire, I.; Caillaud, C.; Levade, T.; Chabrol, B.; Feillet, F.; Ogier, H.; et al. Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am. J. Med. Genet. Part A 2011, 155, 58–68. [Google Scholar] [CrossRef]
- Wassink, T.H.; Piven, J.; Patil, S.R. Chromosomal abnormalities in a clinic sample of individuals with autistic disorder. Psychiatr. Genet. 2001, 11, 57–63. [Google Scholar] [CrossRef]
- Jacquemont, M.L.; Sanlaville, D.; Redon, R.; Raoul, O.; Comier-Daire, V.; Lyonnet, S.; Amiel, J.; Le Merrer, M.; Heron, D.; De Blois, M.C.; et al. Array-based comparative genomic hybridization identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J. Med. Genet. 2006, 43, 843–849. [Google Scholar] [CrossRef]
- Toma, C. Genetic variation across phenotypic severity of autism. Trends Genet. 2020, 36, 228–231. [Google Scholar] [CrossRef]
- Nayar, K.; Sealock, J.M.; Maltman, N.; Bush, L.; Cook, E.H.; Davis, L.K.; Losh, M. Elevated polygenic burden for ASD is associated with the broad autism phenotype in mothers of individuals with ASD. Biol. Psychiatry 2020, in press. [Google Scholar] [CrossRef]
- Malfait, F.; Francomano, C.; Byers, P.; Belmont, J.; Berglund, B.; Black, J.; Bloom, L.; Bowen, J.M.; Brady, A.F.; Burrows, N.P.; et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017, 175, 8–26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malfait, F.; Castori, M.; Francomano, C.A.; Giunta, C.; Kosho, T.; Byers, P.H. The Ehlers-Danlos syndromes. Nat. Rev. Dis. Primers 2020, 6, 63. [Google Scholar] [CrossRef] [PubMed]
- Tinkle, B.; Castori, M.; Berglund, B.; Cohen, H.; Grahame, R.; Kazkaz, H.; Levy, H. Hypermobile Ehlers-Danlos syndrome (aka Ehlers-Danlos syndrome type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017, 175, 48–69. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Casanova, E.L.; Sharp, J.L.; Edelson, S.M.; Kelly, D.P.; Sokhadze, E.M.; Casanova, M.F. Immune, autonomic, and endocrine dysregulation in autism and Ehlers-Danlos syndrome/hypermobility spectrum disorders versus unaffected controls. J. Reatt. Ther. Dev. Divers. 2020, 2, 82–95. [Google Scholar]
- The Ehlers-Danlos Society. Hypermobile Ehlers-Danlos Genetic Evaluation (HEDGE) Study. Available online: https://www.ehlers-danlos.com/hedge/ (accessed on 25 September 2020).
- Copetti, M.; Morlino, S.; Colombi, M.; Grammatico, P.; Fontana, A.; Castori, M. Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: A pilot study of 105 Italian patients. Rheumatology 2019, 58, 1722–1730. [Google Scholar] [CrossRef] [PubMed]
- Tinkle, B.T.; Bird, H.A.; Grahame, R.; Lavallee, M.; Levy, H.P.; Sillence, D. The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome). Am. J. Med. Genet. Part A 2009, 149, 2368–2370. [Google Scholar] [CrossRef]
- Castori, M.; Dordoni, C.; Valiante, M.; Sperduti, I.; Ritelli, M.; Morlino, S.; Chiarelli, N.; Celletti, C.; Venturini, M.; Camerota, F.; et al. Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type: A study of intrafamilial and interfamilial variability in 23 Italian pedigrees. Am. J. Med. Genet. Part A 2014, 164, 3010–3020. [Google Scholar] [CrossRef]
- Fehlow, P.; Bernstein, K.; Tennstedt, A.; Walther, F. Early infantile autism and excessive aerophagy with symptomatic megacolon and ileus in a case of Ehlers-Danlos syndrome. Padiatr. Grenzegebiete 1993, 31, 259–267. [Google Scholar]
- Sieg, K.G. Autism and Ehlers-Danlos syndrome. J. Am. Med. Acad. Child Adolesc. Psychiatry 1992, 31, 173. [Google Scholar] [CrossRef] [PubMed]
- Takei, A.; Mera, K.; Sato, Y.; Haraoka, Y. High-functioning autistic disorder with Ehlers-Danlos syndrome. Psychiatry Clin. Neurosci. 2011, 65, 605–606. [Google Scholar] [CrossRef] [PubMed]
- Cederlöf, M.; Larsson, H.; Lichtenstein, P.; Almqvist, C.; Serlachius, E.; Ludvigsson, J.F. Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings. BMC Psychiatry 2016, 16, 207. [Google Scholar] [CrossRef] [Green Version]
- Eccles, J.A.; Iodice, V.; Dowell, N.G.; Owens, A.; Hughes, L.; Skipper, S.; Lycette, Y.; Humphries, K.; Harrison, N.A.; Mathias, C.J.; et al. Joint hypermobility and autonomic hyperactivity: Relevance to neurodevelopmental disorders. J. Neurol. Neurosurg. Psychiatry 2014, 85, e3. [Google Scholar] [CrossRef]
- Csecs, J.L.; Iodice, V.; Rae, C.L.; Brooke, A.; Simmons, R.; Dowell, N.G.; Prowse, F.; Themelis, K.; Critchley, H.D.; Eccles, J.A. Increased rate of joint hypermobility in autism and related neurodevelopmental conditions is linked to dysautonomia and pain. medRxiv 2020. [Google Scholar] [CrossRef]
- Doğan, Ş.K.; Taner, Y.; Evcik, D. Benign joint hypermobility syndrome in patients with attention deficit/hyperactivity disorders. Arch. Rheumatol. 2011, 26, 187–192. [Google Scholar] [CrossRef]
- Baeza-Velasco, C.; Cohen, D.; Hamonet, C.; Vlamynck, E.; Diaz, L.; Cravero, C.; Cappe, E.; Guinchat, V. Autism, joint hypermobility-related disorders and pain. Front. Psychiatry 2018, 9, 656. [Google Scholar] [CrossRef]
- Gould, J.; Ashton-Smith, J. Missed diagnosis or misdiagnosis? Girls and women on the autism spectrum. Good Autism Pract. (Gap) 2011, 12, 34–41. [Google Scholar]
- Green, R.M.; Travers, A.M.; Howe, Y.; McDougle, C.J. Women and autism spectrum disorder: Diagnosis and implications for treatment of adolescents and adults. Curr. Psychiatry Rep. 2019, 21, 22. [Google Scholar] [CrossRef]
- Lai, M.C.; Lombardo, M.V.; Ruigrok, A.N.; Chakrabarti, B.; Auyeung, B.; Szatmari, P.; Happé, F.; Baron-Cohen, S.; MRC AIMS Consortium. Quantifying and exploring camouflaging in men and women with autism. Autism 2017, 21, 690–702. [Google Scholar] [CrossRef] [Green Version]
- Castori, M.; Camerota, F.; Celletti, C.; Grammatico, P.; Padua, L. Ehlers-Danlos syndrome hypermobility type and the excess of affected females: Possible mechanisms and perspectives. Am. J. Med. Genet. Part A 2010, 152, 2406–2408. [Google Scholar] [CrossRef] [PubMed]
- Careaga, M.; Murai, T.; Bauman, M.D. Maternal immune activation and autism spectrum disorder: From rodents to nonhuman and human primates. Biol. Psychiatry 2017, 81, 391–401. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gröbner, R.; Kapferer-Seebacher, I.; Amberger, A.; Redolfi, R.; Dalonneau, F.; Björck, E.; Milnes, D.; Bally, I.; Rossi, V.; Thielens, N.; et al. C1R mutations trigger constitutive complement 1 activation in periodontal Ehlers-Danlos syndrome. Front. Immunol. 2019, 10, 2537. [Google Scholar] [CrossRef] [Green Version]
- Mataix, J.; Bañuls, J.; Muñoz, C.; Bermejo, A.; Climent, J.M. Periodontal Ehlers-Danlos syndrome associated with type III and I collagen deficiencies. Br. J. Dermatol. 2008, 158, 825–830. [Google Scholar] [CrossRef] [PubMed]
- Tassanakijpanich, N.; McKenzie, F.J.; McLennan, Y.A.; Makhoul, E.; Tassone, F.; Jasoliya, M.J.; Romney, C.; Cortina Petrasic, I.; Napalinga, K.; Buchanan, C.; et al. Hypermobile Ehlers-Danlos syndrome (hEDS) phenotype in fragile X premutation carriers: Case series. 2020. under submission. [Google Scholar]
- Hagerman, R.J.; Van Housen, K.; Smith, A.C.; McGavran, L.; Opitz, J.M. Consideration of connective tissue dysfunction in the fragile X syndrome. Am. J. Med. Genet. 1984, 17, 111–121. [Google Scholar] [CrossRef] [PubMed]
- Dziembowska, M.; Pretto, D.I.; Janusz, A.; Kaczmarek, L.; Leigh, M.J.; Gabriel, N.; Durbin-Johnson, B.; Hagerman, R.J.; Tassone, F. High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am. J. Med. Genet. Part A 2013, 161, 1897–1903. [Google Scholar] [CrossRef]
- Rao, V.H.; Kansal, V.; Stoupa, S.; Agrawal, D.K. MMP-1 and MMP-9 regulate epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells. Physiol. Rep. 2014, 2, e00224. [Google Scholar] [CrossRef]
- Bisgaard, A.-M.; Schönewolf-Greulich, B.; Ravn, K.; Rønde, G. Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012. Eur. J. Paediatr. Neurol. 2015, 19, 679–687. [Google Scholar] [CrossRef]
- Hu, B.; Gharaee-Kermani, M.; Wu, Z.; Phan, S.H. Essential role of MeCP2 in the regulation of myofibroblast differentiation during pulmonary fibrosis. Am. J. Pathol. 2011, 178, 1500–1508. [Google Scholar] [CrossRef]
- Signorini, C.; Leoncini, S.; De Felice, C.; Pecorelli, A.; Meloni, I.; Ariani, F.; Mari, F.; Amabile, S.; Paccagnini, E.; Gentile, M.; et al. Redox imbalance and morphological changes in skin fibroblasts in typical Rett syndrome. Oxidative Med. Cell. Longev. 2014, 2014, 195935. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Online Mendelian Inheritance in Man, OMIM. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD). 2020. Available online: https://omim.org/ (accessed on 11 May 2020).
- Warde-Farley, D.; Donaldson, S.L.; Comes, O.; Zuberi, K.; Badrawi, R.; Chao, P.; Franz, M.; Grouios, C.; Kazi, F.; Lopes, T.; et al. The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010, 38, W214–W220. [Google Scholar] [CrossRef]
- Brookman-Frazee, L.; Stadnick, N.; Chlebowski, C.; Baker-Ericzén, M.; Ganger, W. Characterizing psychiatric comorbidity in children with autism spectrum disorder receiving publicly funded mental health services. Autism 2017, 22, 938–952. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, G.; Pearson, J. Autism and learning disability. Autism 2004, 8, 125–140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baeza-Velasco, C.; Grahame, R.; Bravo, J.F. A connective tissue disorder may underlie ESSENCE problems in childhood. Res. Dev. Disabil. 2017, 60, 232–242. [Google Scholar] [CrossRef] [PubMed]
- Baeza-Velasco, C.; Sinibaldi, L.; Castori, M. Attention deficit/hyperactivity disorder, joint hypermobility related disorders and pain: Expanding body-mind connections to the developmental age. Atten. Deficit Hyperact. Disord. 2018, 10, 163–175. [Google Scholar] [CrossRef]
- Piedimonte, C.; Penge, R.; Morlino, S.; Sperduti, I.; Terzani, A.; Giannini, M.T.; Colombi, M.; Grammatico, P.; Cardona, F.; Castori, M. Exploring relationships between joint hypermobility and neurodevelopment in children (4–13 years) with hereditary connective tissue disorders and developmental coordination disorder. Am. J. Med. Genet. B 2018, 177, 546–556. [Google Scholar] [CrossRef]
- Darrow, S.M.; Grados, M.; Sandor, P.; Hirschtritt, M.E.; Illmann, C.; Osiecki, L.; Dion, Y.; King, R.; Pauls, D.; Budman, C.L.; et al. Autism Spectrum Symptoms in a Tourette’s Disorder Sample. J. Am. Acad. Child Adolesc. Psychiatry 2017, 56, 610–617.e1. [Google Scholar] [CrossRef] [Green Version]
- Adib, N.; Davies, R.; Grahame, R.; Woo, P.; Murray, K.J. Joint hypermobility syndrome in childhood. A not so benign multisystem disorder? Rheumatology 2005, 44, 744–750. [Google Scholar] [CrossRef] [Green Version]
- Ghibellini, G.; Brancati, F.; Castori, M. Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives. Am. J. Med. Genet. Part C Semin. Med. Genet. 2015, 169, 107–116. [Google Scholar] [CrossRef]
- Karas, B.; Grubb, B.P.; Boehm, K.; Kip, K. The Postural Orthostatic Tachycardia Syndrome: A potentially treatable cause of chronic fatigue, exercise intolerance, and cognitive impairment in adolescents. Pacing Clin. Electrophysiol. 2000, 23, 344–351. [Google Scholar] [CrossRef] [PubMed]
- Moriarty, O.; McGuire, B.E.; Finn, D.P. The effect of pain on cognitive function: A review of clinical and preclinical research. Prog. Neurobiol. 2011, 93, 385–404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baeza-Velasco, C. Neurodiversity: Associations and implications in hypermobility spectrum disorders and Ehlers-Danlos syndrome. In Proceedings of the EDS ECHO Summit. Scientific Meeting on EDS, HSD and Co-Morbidities (Virtual Event), 2–3 October 2020. [Google Scholar]
- Postorino, V.; Kerns, C.M.; Vivanti, G.; Bradshaw, J.; Siracusano, M.; Mazzone, L. Anxiety Disorders and Obsessive-Compulsive Disorder in Individuals with Autism Spectrum Disorder. Curr. Psychiatry Rep. 2017, 19, 92. [Google Scholar] [CrossRef] [PubMed]
- Bulbena, A.; Baeza-Velasco, C.; Bulbena-Cabré, A.; Pailhez, G.; Critchley, H.; Chopra, P.; Mallorqui-Bagué, N.; Frank, C.; Porges, S. Psychiatric and psychological aspects in the Ehlers-Danlos syndrome. Am. J. Med. Genet. Part C 2017, 175, 237–245. [Google Scholar] [CrossRef] [Green Version]
- Van Heijst, B.F.C.; Deserno, M.K.; Rhebergen, D.; Geurts, H.M. Autism and depression are connected: A report of two complementary network studies. Autism 2020, 24, 680–692. [Google Scholar] [CrossRef]
- Munesue, T.; Ono, Y.; Mutoh, K.; Shimoda, K.; Nakatani, H.; Kikuchi, M. High prevalence of bipolar disorder comorbidity in adolescents and young adults with high-functioning autism spectrum disorder: A preliminary study of 44 outpatients. J. Affect. Disord. 2008, 111, 170–175. [Google Scholar] [CrossRef]
- Vuiller, L.; Carter, Z.; Teixeira, A.R.; Moseley, R.L. Alexithymia may explain the relationship between autistic traits and eating disorder psychopathology. Mol. Autism 2020, 11, 63. [Google Scholar] [CrossRef]
- Baeza-Velasco, C.; Lorente, S.; Tasa Vindral, B.; Guillaume, S.; Mora, M.; Espinoza, P. Gastrointestinal and eating problems in women with Ehlers-Danlos syndromes. 2020. under submission. [Google Scholar]
- Storch, E.A.; Sulkowski, M.L.; Nadeau, J.; Lewin, A.B.; Arnold, E.B.; Mutch, P.J.; Murphy, T.K. The phenomenology and clinical correlates of suicidal thoughts and behaviors in youth with autism spectrum disorders. J. Autism Dev. Disord. 2013, 43, 2450–2459. [Google Scholar] [CrossRef]
- Bal, E.; Harden, E.; Lamb, D.; Van Hecke, A.V.; Denver, J.W.; Porges, S.W. Emotion recognition in children with autism spectrum disorders: Relations to eye gaze and autonomic state. J. Autism Dev. Disord. 2010, 40, 358–370. [Google Scholar] [CrossRef]
- Anderson, J.W.; Lambert, E.A.; Sari, C.I.; Dawood, T.; Esler, M.D.; Vaddadi, G.; Lambert, G.W. Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with postural orthostatic tachycardia syndrome (POTS). Front. Physiol. 2014, 5, 230. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Strasser, L.; Downes, M.; Kung, J.; Cross, J.H.; De Haan, M. Prevalence and risk factors for autism spectrum disorder in epilepsy: A systematic review and meta-analysis. Dev. Med. Child Neurol. 2018, 60, 19–29. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spence, S.J.; Schneider, M.T. The role of epilepsy and epileptiform EEGs in autism spectrum disorders. Pediatrics Res. 2009, 65, 599–606. [Google Scholar] [CrossRef]
- Amiet, C.; Gourfinkel-An, I.; Bouzamondo, A.; Tordjman, S.; Baulac, M.; Lechat, P.; Mottron, L.; Cohen, D. Epilepsy in autism is associated with intellectual disability and gender: Evidence from a meta-analysis. Biol. Psychiatry 2008, 64, 577–582. [Google Scholar] [CrossRef] [PubMed]
- Cortini, F.; Villa, C. Ehlers-Danlos syndromes and epilepsy: An updated review. Seizure 2018, 57, 1–4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Castori, M.; Voermans, N.C. Neurological manifestations of Ehlers-Danlos syndrome(s): A review. Iran. J. Neurol. 2014, 13, 190–208. [Google Scholar]
- Wegiel, J.; Kuchna, I.; Nowicki, K.; Imaki, H.; Wegiel, J.; Marchi, E.; Ma, S.Y.; Chauhan, A.; Chauhan, V.; Bobrowicz, T.W.; et al. The neuropathology of autism: Defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol. 2010, 119, 755–770. [Google Scholar] [CrossRef] [Green Version]
- Hamonet, C.; Fredy, D.; Lefevre, J.H.; Bourgeois-Gironde, S.; Zeiton, J.-D. Brain injury unmasking Ehlers-Danlos syndromes after trauma: The fiber print. Orphanet J. Rare Dis. 2016, 11, 45. [Google Scholar] [CrossRef] [Green Version]
- Chang, H.K.; Hsu, J.W.; Wu, J.C.; Huang, K.L.; Chang, H.C.; Bai, Y.M.; Chen, T.J.; Chen, M.H. Traumatic brain injury in early childhood and risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: A nationwide longitudinal study. J. Clin. Psychiatry 2018, 79, 17m11857. [Google Scholar] [CrossRef]
- Goldman, S.E.; Richdale, A.L.; Clemons, T.; Malow, B.A. Parental sleep concerns in autism spectrum disorders: Variations from childhood to adolescence. J. Autism Dev. Disord. 2012, 42, 531–538. [Google Scholar] [CrossRef]
- Richdale, A.L.; Schreck, K.A. Sleep problems in autism spectrum disorders: Prevalence, nature, & possible biopsychosocial aetiologies. Sleep Med. Rev. 2009, 13, 403–411. [Google Scholar]
- Domany, K.A.; Hantragool, S.; Smith, D.F.; Xu, Y.; Hossain, M.; Simakajornboon, N. Sleep disorders and their management in children with Ehlers-Danlos syndrome referred to sleep clinics. J. Clin. Sleep Med. 2018, 14, 623–629. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guilleminault, C.; Primeau, M.; Chiu, H.-Y.; Yuen, K.M.; Leger, D.; Metlaine, A. Sleep-disordered breathing in Ehlers-Danlos syndrome: A genetic model of OSA. Chest 2013, 144, 1503–1511. [Google Scholar] [CrossRef] [PubMed]
- Gaisl, T.; Giunta, C.; Bratton, D.J.; Sutherland, K.; Schlatzer, C.; Sievi, N.; Franzen, D.; Cistulli, P.A.; Rohrbach, M.; Kohler, M. Obstructive sleep apnoea and quality of life in Ehlers-Danlos syndrome: A parallel cohort study. Thorax 2017, 72, 729–735. [Google Scholar] [CrossRef]
- Elrod, M.G.; Nylund, C.M.; Susi, A.L.; Gorman, G.H.; Hisle-Gorman, E.; Rogers, D.J.; Erdie-Lalena, C. Prevalence of diagnosed sleep disorders and related diagnostic and surgical procedures in children with autism spectrum disorders. J. Dev. Behav. Pediatrics 2016, 37, 377–384. [Google Scholar] [CrossRef]
- Fournier, K.A.; Hass, C.J.; Naik, S.K.; Lodha, N.; Cauraugh, J.H. Motor coordination in autism spectrum disorders: A synthesis and meta-analysis. J. Autism Dev. Disord. 2010, 40, 1227–1240. [Google Scholar] [CrossRef] [PubMed]
- Harris, S.R. Early motor delays as diagnostic clues in autism spectrum disorder. Eur. J. Pediatrics 2017, 176, 1259–1262. [Google Scholar] [CrossRef] [PubMed]
- Lloyd, M. Motor skills of toddlers with autism spectrum disorders. Autism 2013, 17, 133–146. [Google Scholar] [CrossRef] [Green Version]
- Sumner, E.; Leonard, H.C.; Hill, E.L. Overlapping phenotypes in autism spectrum disorder and developmental coordination disorder: A cross-syndrome comparison of motor and social skills. J. Autism Dev. Disord. 2016, 46, 2609–2620. [Google Scholar] [CrossRef] [Green Version]
- Kopp, S.; Beckung, E.; Gillberg, C. Developmental coordination disorder and other motor control problems in girls with autism spectrum disorder and/or attention-deficit/hyperactivity disorder. Res. Dev. Disabil. 2010, 31, 350–361. [Google Scholar] [CrossRef]
- Mon-Williams, M.A.; Wann, J.P.; Pascal, E. Visual-proprioceptive mapping in children with developmental coordination disorder. Dev. Med. Child Neurol. 1999, 41, 247–254. [Google Scholar] [CrossRef] [PubMed]
- Tseng, Y.T.; Tsai, C.L.; Chen, F.C.; Konczak, J. Wrist position sense acuity and its relation to motor dysfunction in children with developmental coordination disorder. Neurosci. Lett. 2018, 674, 106–111. [Google Scholar] [CrossRef] [PubMed]
- Tseng, Y.T.; Tsai, C.L.; Chen, F.C.; Chen, F.C.; Konczak, J. Position sense dysfunction affects proximal and distal arm joints in children with developmental coordination disorder. J. Mot. Behav. 2019, 51, 49–58. [Google Scholar] [CrossRef]
- Blanche, E.I.; Reinoso, G.; Chang, M.C.; Bodison, S. Proprioceptive processing difficulties among children with autism spectrum disorders and developmental disabilities. Am. J. Occup. Ther. 2012, 66, 621–624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Riquelme, I.; Hatem, S.M.; Montoya, P. Abnormal pressure pain, touch sensitivity, proprioception, and manual dexterity in children with autism spectrum disorders. Neural Plast. 2016, 2016, 1723401. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clayton, H.A.; Cressman, E.K.; Henriques, D.Y. Proprioceptive sensitivity in Ehlers-Danlos syndrome patients. Exp. Brain Res. 2013, 230, 311–321. [Google Scholar] [CrossRef]
- Clayton, H.A.; Jones, S.A.; Henriques, D.Y. Proprioceptive precision is impaired in Ehlers-Danlos syndrome. SpringerPlus 2015, 4, 323. [Google Scholar] [CrossRef] [Green Version]
- Chien, Y.L.; Chao, C.C.; Wu, S.W.; Hsueh, H.W.; Chiu, Y.N.; Tsai, W.C.; Gau, S.S.F.; Hsieh, S.T. Small fiber pathology in autism and clinical implications. Neurology 2020. [Google Scholar] [CrossRef]
- Silva, L.; Schalock, M. First skin biopsy reports in children with autism show loss of C-tactile fibers. J. Neurol. Disord. 2016, 4, 2. [Google Scholar] [CrossRef] [Green Version]
- Skilling, S.R.; Harkness, D.H.; Larson, A.A. Experimental peripheral neuropathy decreases the dose of substance P required to increase excitatory amino acid release in the CSF of the rat spinal cord. Neurosci. Lett. 1992, 139, 92–96. [Google Scholar] [CrossRef]
- Rombaut, L.; Scheper, M.; De Wandele, I.; De Vries, J.; Meeus, M.; Malfait, F.; Engelbert, R.; Calders, P. Chronic pain in patients with the hypermobility type of Ehlers-Danlos syndrome: Evidence for generalized hyperalgesia. Clin. Rheumatol. 2015, 34, 1121–1129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cazzato, D.; Castori, M.; Lombardi, R.; Caravello, F.; Dalla Bella, E.; Petrucci, A.; Grammatico, P.; Dordoni, C.; Colombi, M.; Lauria, G. Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes. Neurology 2016, 87, 155–159. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Camerota, F.; Celletti, C.; Castori, M.; Grammatico, P.; Padua, L. Neuropathic pain is a common feature in Ehlers-Danlos syndrome. J. Pain Symptom Manag. 2011, 41, e2–e4. [Google Scholar] [CrossRef] [PubMed]
- Granata, G.; Padua, L.; Celletti, C.; Castori, M.; Saraceni, V.M.; Camerota, F. Entrapment neuropathies and polyneuropathies in joint hypermobility syndrome/Ehlers-Danlos syndrome. Clin. Neurophysiol. 2013, 124, 1689–1694. [Google Scholar] [CrossRef] [PubMed]
- Syx, D.; Miller, R.E.; Obeidat, A.M.; Tran, P.B.; Vroman, R.; Malfait, Z.; Miller, R.J.; Malfait, F.; Malfait, A.M. Pain-related behaviors and abnormal cutaneous innervation in a murine model of classical Ehlers-Danlos syndrome. Pain 2020, 161, 2274–2283. [Google Scholar] [CrossRef]
- Minshew, N.J.; Hobson, J.A. Sensory sensitivities and performance on sensory perceptual tasks in high-functioning individuals with autism. J. Autism Dev. Disord. 2008, 38, 1485–1498. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fedorowski, A. Postural orthostatic tachycardia syndrome: Clinical presentation, aetiology and management. J. Intern. Med. 2019, 285, 352–366. [Google Scholar] [CrossRef]
- Goswami, R.; Frances, M.F.; Steinback, C.D.; Shoemaker, J.K. Forebrain organization representing baroreceptor gating of somatosensory afferents within the cortical autonomic network. J. Neurophysiol. 2012, 108, 453–466. [Google Scholar] [CrossRef] [Green Version]
- Stewart, J.M. Autonomic nervous system dysfunction in adolescents with postural orthostatic tachycardia syndrome and chronic fatigue syndrome is characterized by attenuated vagal baroreflex and potentiated sympathetic vasomotion. Pediatric Res. 2000, 48, 218–226. [Google Scholar] [CrossRef] [Green Version]
- Henderson, F.C., Sr.; Austin, C.; Benzel, E.; Bolognese, P.; Ellenbogen, R.; Francomano, C.A.; Ireton, C.; Klinge, P.; Koby, M.; Long, M.; et al. Neurological and spinal manifestations of the Ehlers-Danlos syndromes. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017, 175, 195–211. [Google Scholar] [CrossRef] [Green Version]
- Jayarao, M.; Sohl, K.; Tanaka, T. Chiari malformation I and autism spectrum disorder: An underrecognized coexistence. J. Neurosurg. Pediatrics 2015, 15, 96–100. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kushki, A.; Drumm, E.; Mobarak, M.P.; Tanel, N.; Dupuis, A.; Chau, T.; Anagnostou, E. Investigating the autonomic nervous system response to anxiety in children with autism spectrum disorders. PLoS ONE 2013, 8, e59730. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vernetti, A.; Shic, F.; Boccanfuso, L.; Macari, S.; Kane-Grade, F.; Milgramm, A.; Hilton, E.; Heymann, P.; Goodwin, M.S.; Chawarska, K. Atypical emotional electrodermal activity in toddlers with autism spectrum disorder. Autism Res. 2020, in press. [Google Scholar] [CrossRef] [PubMed]
- Hirstein, W.; Iversen, P.; Ramachandran, V.S. Autonomic responses of autistic children to people and objects. Proc. R. Soc. Lond. Ser. B Biol. Sci. 2001, 268, 1883–1888. [Google Scholar] [CrossRef] [PubMed]
- Bricout, V.A.; Pace, M.; Dumortier, L.; Favre-Juvin, A.; Guinot, M. Autonomic responses to head-up tilt test in children with autism spectrum disorders. J. Abnorm. Child Psychol. 2018, 46, 1121–1128. [Google Scholar] [CrossRef]
- Anderson, C.J.; Colombo, J. Larger tonic pupil size in young children with autism spectrum disorder. Dev. Psychobiol. J. Int. Soc. Dev. Psychobiol. 2009, 51, 207–211. [Google Scholar] [CrossRef]
- Zahn, T.P.; Rumsey, J.M.; Van Kammen, D.P. Autonomic nervous system activity in autistic, schizophrenic, and normal men: Effects of stimulus significance. J. Abnorm. Psychol. 1987, 96, 135. [Google Scholar] [CrossRef]
- Harder, R.; Malow, B.A.; Goodpaster, R.L.; Igbal, F.; Halbower, A.; Goldman, S.E.; Fawkes, D.B.; Wang, L.; Shi, Y.; Baudenbacher, F.; et al. Heart rate variability during sleep in children with autism spectrum disorder. Clin. Auton. Res. 2016, 26, 423–432. [Google Scholar] [CrossRef] [Green Version]
- O’Haire, M.E.; McKenzie, S.J.; Beck, A.M.; Slaughter, V. Animals may act as social buffers: Skin conductance arousal in children with autism spectrum disorder in a social context. Dev. Psychobiol. 2015, 57, 584–595. [Google Scholar] [CrossRef]
- Tessier, M.P.; Pennestri, M.H.; Godbout, R. Heart rate variability of typically developing and autistic children and adults before, during and after sleep. Int. J. Psychophysiol. 2018, 134, 15–21. [Google Scholar] [CrossRef]
- Guy, L.; Souders, M.; Bradstreet, L.; DeLussey, C.; Herrington, J.D. Brief report: Emotion regulation and respiratory sinus arrthythmia in autism spectrum disorder. J. Autism Dev. Disord. 2014, 44, 2614–2620. [Google Scholar] [CrossRef]
- Ferguson, B.J.; Marler, S.; Altstein, L.L.; Batey Lee, E.; Akers, J.; Sohl, K.; McLaughlin, A.; Hartnett, K.; Kille, M.; Mazurek, M.; et al. Psychophysiological associations with gastrointestinal symptomatology in autism spectrum disorder. Autism Res. 2016, 10, 276–288. [Google Scholar] [CrossRef]
- Sagar-Ouriaghli, I.; Lievesley, K.; Santosh, P.J. Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders. J. Psychopharmacol. 2018, 32, 641–653. [Google Scholar] [CrossRef] [PubMed]
- Emin, O.; Esra, G.; Aysegül, D.; Ufuk, E.; Ayhan, S.; Rusen, D.M. Autonomic nervous system dysfunction and their relationship with disease severity in children with atopic asthma. Respir. Physiol. Neurobiol. 2012, 183, 206–210. [Google Scholar] [CrossRef] [PubMed]
- Casanova, M.F.; Hensley, M.K.; Sokhadze, E.M.; El-Baz, A.S.; Wang, Y.; Li, X.; Sears, L. Effects of weekly low-frequency rTMS on autonomic measures in children with autism spectrum disorder. Front. Hum. Neurosci. 2014, 8, 851. [Google Scholar] [CrossRef] [Green Version]
- Sokhadze, G.; Casanova, M.F.; Kelly, D.; Casanova, E.; Russell, B.; Sokhadze, E.M. Neuromodulation based on rTMS affects behavioral measures and autonomic nervous system activity in children with autism. NeuroRegulation 2017, 4, 65. [Google Scholar] [CrossRef] [Green Version]
- De Wandele, I.; Calders, P.; Peersman, W.; Rimbaut, S.; De Backer, T.; Malfait, F.; De Paepe, A.; Rombaut, L. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: A comparative study with two other EDS types, fibromyalgia, and health controls. Semin. Arthritis Rheum. 2014, 44, 353–361. [Google Scholar] [CrossRef]
- De Wandele, I.; Rombaut, L.; Leybaert, L.; Van de Borne, P.; De Backer, T.; Malfait, F.; De Paepe, A.; Calders, P. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Semin. Arthritis Rheum. 2014, 44, 93–100. [Google Scholar] [CrossRef]
- Hakim, A.; O’Callaghan, C.; De Wandele, I.; Stiles, L.; Pocinki, A.; Rowe, P. Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome—Hypermobile type. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017, 175, 168–174. [Google Scholar] [CrossRef] [Green Version]
- Health Quality Ontario. Positional magnetic resonance imaging for people with Ehlers-Danlos syndrome or suspected craniovertebral or cervical spine abnormalities: An evidence-based analysis. Ont. Health Technol. Assess. Ser. 2015, 15, 1. [Google Scholar]
- Onore, C.; Careaga, M.; Ashwood, P. The role of immune dysfunction in the pathophysiology of autism. Brain Behav. Immun. 2012, 26, 383–392. [Google Scholar] [CrossRef] [Green Version]
- Ahmad, S.F.; Zoheir, K.M.; Ansari, M.A.; Nadeem, A.; Bakheet, S.A.; Al-Ayadhi, L.Y.; Alzahrani, M.Z.; Al-Shabanah, O.A.; Al-Harbi, M.M.; Attia, S.M. Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism. Mol. Neurobiol. 2017, 54, 4390–4400. [Google Scholar] [CrossRef] [PubMed]
- Jones, K.L.; Crown, L.A.; Yoshida, C.K.; Heuer, L.; Hansen, R.; Zerbo, O.; DeLorenze, G.N.; Kharrazi, M.; Yolken, R.; Ashwood, P.; et al. Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Mol. Psychiatry 2017, 22, 273–279. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smith, S.E.; Elliott, R.M.; Anderson, M.P. Maternal immune activation increases neonatal mouse cortex thickness and cell density. J. Neuroimmune Pharmacol. 2012, 7, 529–532. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gallagher, D.; Norman, A.A.; Woodard, C.L.; Yang, G.; Gauthier-Fisher, A.; Fujitani, M.; Vessey, J.P.; Cancino, G.I.; Sachewsky, N.; Woltjen, K. Transient maternal IL-6 mediates long-lasting changes in neural stem cell pools by deregulating an endogenous self-renewal pathway. Cell Stem Cell 2013, 13, 564–576. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ecker, C.; Ginestet, C.; Feng, Y.; Johnston, P.; Lombardo, M.V.; Lai, M.C.; Suckling, J.; Palaniyappan, L.; Daly, E.; Murphy, C.M.; et al. Brain surface anatomy in adults with autism: The relationship between surface area, cortical thickness, and autistic symptoms. JAMA Psychiatry 2013, 70, 59–70. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zielinski, B.A.; Prigge, M.B.; Nielsen, J.A.; Froehlich, A.L.; Abildskov, T.J.; Anderson, J.S.; Fletcher, P.T.; Zygmut, K.M.; Travers, B.G.; Lange, N.; et al. Longitudinal changes in cortical thickness in autism and typical development. Brain 2014, 137, 1799–1812. [Google Scholar] [CrossRef] [Green Version]
- Seneviratne, S.L.; Maitland, A.; Afrin, L. Mast cell disorders in Ehlers-Danlos syndrome. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017, 175, 226–236. [Google Scholar] [CrossRef] [Green Version]
- Chang, A.R.; Vadas, P. Prevalence of symptoms of mast cell activation in patients with postural orthostatic tachycardia syndrome and hypermobile Ehlers-Danlos syndrome. J. Allergy Clin. Immunol. 2019, 143, AB182. [Google Scholar] [CrossRef]
- Chiarelli, N.; Ritelli, M.; Zoppi, N.; Colombi, M. Cellular and molecular mechanisms in the pathogenesis of classical, vascular, and hypermobile Ehlers-Danlos syndromes. Genes 2019, 10, 609. [Google Scholar] [CrossRef] [Green Version]
- Chou, D.H.; Lee, W.; McCulloch, C.A. TNF-alpha inactivation of collagen receptors: Implications for fibroblast function and fibrosis. J. Immunol. 1996, 156, 4354–4362. [Google Scholar] [PubMed]
- Duncan, M.R.; Berman, B. Differential regulation of collagen, glycosaminoglycan, fibronectin, and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1-alpha and beta and tumor necrosis factor-alpha and beta. J. Investig. Dermatol. 1989, 92, 699–706. [Google Scholar] [CrossRef] [Green Version]
- Winarni, T.I.; Chonchaiya, W.; Sumekar, T.A.; Ashwood, P.; Morales, G.M.; Tassone, F.; Nguyen, D.V.; Faradz, S.M.; Van de Water, J.; Cook, K.; et al. Immune-mediated disorders among women carriers of fragile X premutation alleles. Am. J. Med. Genet. Part A 2012, 158, 2473–2481. [Google Scholar] [CrossRef] [Green Version]
- Careaga, M.; Rose, D.; Tassone, F.; Berman, R.F.; Hagerman, R.; Ashwood, P. Immune dysregulation as a cause of autoinflammation in fragile X premutation carriers: Link between FMR1 CGG repeat number and decreased cytokine responses. PLoS ONE 2014, 9, e94475. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jalnapurkar, I.; Rafika, N.; Tassone, F.; Hagerman, R. Immune mediated disorders in women with a fragile X expansion and FXTAS. Am. J. Med. Genet. Part A 2015, 167, 190–197. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Larsen, C.M.; Juul-Kristensen, B.; Lund, H.; Sogaard, K. Measurement properties of existing clinical assessment methods evaluating scapular positioning and function. A systematic review. Physiother. Theory Pract. 2014, 30, 453–482. [Google Scholar] [CrossRef]
- Engelbert, R.H.H.; Juul-Kristensen, B.; Pacey, V.; de Wandele, I.; Smeenk, S.; Woinarosky, N.; Sabo, S.; Scheper, M.C.; Russek, L.; Simmonds, J.V. The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome. Am. J. Med. Genet. Part C Semin. Med. Genet. 2017, 175, 158–167. [Google Scholar] [CrossRef] [Green Version]
- Ferrell, W.R.; Tennant, N.; Sturrock, R.D.; Ashton, L.; Creed, G.; Brydson, G.; Rafferty, D. Amelioration of symptoms by enhancement of proprioception in patients with joint hypermobility syndrome. Arthritis Rheum. 2004, 50, 3323–3328. [Google Scholar] [CrossRef]
OMIM # | Syndrome | Gene/Locus | Inheritance | Group |
---|---|---|---|---|
606053 | Intellectual Developmental Disorder with Autism and Speech Delay | TBR1 | AD | Autism/hypermobility |
616603 | Cutis Laxa, Autosomal Dominant 3 | ALDH18A1 | AD | Autism/hypermobility |
618906 | Intellectual Developmental Disorder with Autistic Features and Language Delay, with or without Seizures | TANC2 | AD | Autism/hypermobility |
300624 | Fragile X Syndrome | FMR1 | XLD | Autism/hypermobility |
618718 | Neurodevelopmental Disorder with Behavioral Abnormalities, Absent Speech, and Hypotonia | NTNG2 | AR | Autism/hypermobility |
610443 | Koolen-De Vries Syndrome | KANSL1 | AD | Autism/hypermobility |
615873 | Helsmoortel-Van der AA Syndrome | ADNP | AD | Autism/hypermobility |
615828 | Vulto-Van Silfhout-De Vries Syndrome | DEAF1 | AD | Autism/hypermobility |
300958 | Intellectual Developmental Disorder, X-linked, Syndromic, Snijders Blok Type | DDX3X | XLD, XLR | Autism/hypermobility |
618505 | Neurodevelopmental Disorder with Coarse Facies and Mild Distal Skeletal Abnormalities | KDM6B | AD | Autism/hypermobility |
617804 | Neurodevelopmental Disorder with Severe Motor Impairment and Absent Language | DHX30 | AD | Autism/hypermobility |
180849 | Rubinstein-Taybi Syndrome 1 | CREBBP | AD | Autism/hypermobility |
617140 | ZTTK Syndrome | SON | AD | Autism/hypermobility |
617101 | Intellectual Developmental Disorder with Persistence of Fetal Hemoglobin | BLC11A | AD | Autism/hypermobility |
618354 | Neurodevelopmental Disorder and Language Delay with or without Structural Brain Abnormalities | PPP2CA | AD | Autism/hypermobility |
618205 | Snijders Blok-Campeau Syndrome | CHD3 | AD | Autism/hypermobility |
616364 | White-Sitton Syndrome | POGZ | AD | Autism/hypermobility |
613406 | Witteveen-Kolk Syndrome | SIN3A | AD | Autism/hypermobility |
617062 | Oku-Chung Neurodevelopmental Syndrome | CSNK2A1 | AD | Autism/hypermobility |
618659 | Neurodevelopmental Disorder with Dysmorphic Facies and Dystal Skeletal Anomalies | ZMIZ1 | AD | Autism/hypermobility |
617635 | Mental Retardation, Autosomal Dominant 47 | STAG1 | AD | Autism/hypermobility |
617991 | Chung-Jansen Syndrome | PHIP | AD | Autism/hypermobility |
618050 | Mental Retardation, Autosomal Dominant 57 | TLK2 | AD | Autism/hypermobility |
618707 | Neurodevelopmental Disorder with Absent Language and Variable Seizures | WASF1 | AD | Autism/hypermobility |
300986 | Mental Retardation, X-linked, Syndromic, Bain Type | HNRNPH2 | XLD | Autism/hypermobility |
617164 | Short Stature, Rhizomelic, with Microcephaly, Micrognathia, and Developmental Delay | ARCN1 | AD | Autism/hypermobility |
618089 | Intellectual Developmental Disorder with Dysmorphic Facies and Behavioral Abnormalities | FBXO11 | AD | Autism/hypermobility |
618709 | Neurodevelopmental Disorder with Nonspecific Brain Abnormalities, with or without Seizures | DLL1 | AD | Autism/hypermobility |
619000 | Intellectual Developmental Disorder with Seizures and Language Delay | SETB1B | ? | Autism/hypermobility |
617360 | Congenital Heart Defects, Dysmorphic Facial Features, and Intellectual Developmental Disorder | CDK13 | AD | Autism/hypermobility |
300966 | Mental Retardation, X-linked, Syndromic 33 | TAF1 | XLR | Autism/hypermobility |
618748 | Intellectual Developmental Disorder with Hypotonia and Behavioral Abnormalities | CDK8 | AD | Autism/hypermobility |
606232 | Phelan-McDermid Syndrome | SHANK3 | AD | Autism/hypermobility |
619033 | Vissers-Bodmer Syndrome | CNOT1 | ? | Autism/hypermobility |
613684 | Rubinstein-Taybi Syndrome 2 | EP300 | AD | Autism/hypermobility |
130000 | Ehlers-Danlos Syndrome, Classic Type 1 | COL5A1 | AD | Ehlers-Danlos syndrome |
130010 | Ehlers-Danlos Syndrome, Classic Type, 2 | COL5A2 | AD | Ehlers-Danlos syndrome |
606408 | Ehlers-Danlos Syndrome, Classic-like | TNXB | AR | Ehlers-Danlos syndrome |
225320 | Ehlers-Danlos Syndrome, Cardiac Valvular Type | COL1A2 | AR | Ehlers-Danlos syndrome |
130050 | Ehlers-Danlos, Vascular Type | COL3A1 | AD | Ehlers-Danlos syndrome |
130060 | Ehlers-Danlos Syndrome, Arthrochalasia Type, 1 | COL1A1 | AD | Ehlers-Danlos syndrome |
617821 | Ehlers-Danlos Syndrome, Arthrochalasia Type, 2 | COL1A2 | AD | Ehlers-Danlos syndrome |
225410 | Ehlers-Danlos Syndrome, Dermatosparaxis Type | ADAMTS2 | AR | Ehlers-Danlos syndrome |
225400 | Ehlers-Danlos Syndrome, Kyphoscoliotic Type, 1 | PLOD1 | AR | Ehlers-Danlos syndrome |
614557 | Ehlers-Danlos Syndrome, Kyphoscoliotic Type, 2 | FKBP14 | AR | Ehlers-Danlos syndrome |
130070 | Ehlers-Danlos Syndrome, Spondylodysplastic Type, 1 | B4GALT7 | AR | Ehlers-Danlos syndrome |
615349 | Ehlers-Danlos Syndrome Spondylodysplastic Type, 2 | B4GALT6 | AR | Ehlers-Danlos syndrome |
613350 | Ehlers-Danlos Syndrome, Spondylodysplastic Type, 3 | SLC39A13 | AR | Ehlers-Danlos syndrome |
130080 | Ehlers-Danlos Syndrome, Periodontal Type, 1 | C1R | AD | Ehlers-Danlos syndrome |
617174 | Ehlers-Danlos Syndrome, Periodontal Type, 2 | C1S | AD | Ehlers-Danlos syndrome |
616471 | Bethlem Myopathy 2 | COL12A1 | AR | Ehlers-Danlos syndrome |
229200 | Brittle Cornea Syndrome 1 | ZNF469 | AR | Ehlers-Danlos syndrome |
614170 | Brittle Cornea Syndrome 2 | PRDM5 | AR | Ehlers-Danlos syndrome |
610776 | Ehlers-Danlos Syndrome, Musculocontractural Type, 1 | CHST14 | AR | Ehlers-Danlos syndrome |
615539 | Ehlers-Danlos Syndrome, Musculocontractural Type, 2 | DSE | AR | Ehlers-Danlos syndrome |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Casanova, E.L.; Baeza-Velasco, C.; Buchanan, C.B.; Casanova, M.F. The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders. J. Pers. Med. 2020, 10, 260. https://doi.org/10.3390/jpm10040260
Casanova EL, Baeza-Velasco C, Buchanan CB, Casanova MF. The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders. Journal of Personalized Medicine. 2020; 10(4):260. https://doi.org/10.3390/jpm10040260
Chicago/Turabian StyleCasanova, Emily L., Carolina Baeza-Velasco, Caroline B. Buchanan, and Manuel F. Casanova. 2020. "The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders" Journal of Personalized Medicine 10, no. 4: 260. https://doi.org/10.3390/jpm10040260