Autism & EDS/HSD Studies

Posted by A on January 07, 2019 in autism, ehlers-danlos syndrome, hypermobility,

Here is an ongoing compilation of studies related to EDS/HSD & Autism Spectrum Disorders

A Cohort Study Comparing Women with Autism Spectrum Disorder with and without Generalized Joint Hypermobility

Reports suggest comorbidity between autism spectrum disorder (ASD) and the connective tissue disorder, Ehlers-Danlos syndrome (EDS). People with EDS and the broader spectrum of Generalized Joint Hypermobility (GJH) often present with immune- and endocrine-mediated conditions. Meanwhile, immune/endocrine dysregulation is a popular theme in autism research. We surveyed a group of ASD women with/without GJH to determine differences in immune/endocrine exophenotypes. ASD women 25 years or older were invited to participate in an online survey. Respondents completed a questionnaire concerning diagnoses, immune/endocrine symptom history, experiences with pain, and seizure history. ASD women with GJH (ASD/GJH) reported more immune- and endocrine-mediated conditions than their non-GJH counterparts (p = 0.001). Autoimmune conditions were especially prominent in the ASD/GJH group (p = 0.027). Presence of immune-mediated symptoms often co-occurred with one another (p < 0.001–0.020), as did endocrine-mediated symptoms (p < 0.001–0.045), irrespective of the group. Finally, the numbers of immune- and endocrine-mediated symptoms shared a strong inter-relationship (p < 0.001), suggesting potential system crosstalk. While our results cannot estimate comorbidity, they reinforce concepts of an etiological relationship between ASD and GJH. Meanwhile, women with ASD/GJH have complex immune/endocrine exophenotypes compared to their non-GJH counterparts. Further, we discuss how connective tissue regulates the immune system and how the immune/endocrine systems in turn may modulate collagen synthesis, potentially leading to higher rates of GJH in this subpopulation.

A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk. (Marfan's + ASD)

Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases.

Abnormalities of joint mobility and gait in children with autism spectrum disorders

Abnormalities of gross motor function in children with autism are well known to clinicians but have not received much empirical documentation and, with the exception of stereotypies, are not among its diagnostic criteria. We recorded the characteristics of gait and prevalence of toe walking, the range of passive joint mobility, and age at walking in children with DSM IV autism spectrum disorders (ASDs) and in age- and gender-matched typically developing peers (mean age 4 years 6 months, range 22 months–10 years 9 months). Methods: We evaluated maximum range of mobility at the elbow, wrist, metacarpo–phalangeal, and ankle joints and videoed children walking and running. Two neurologists blind to diagnosis independently scored features of gait clinically. Results: Children with ASDs had significantly greater joint mobility (p < .002), more gait abnormalities (p < .0001), and on average walked 1.6 months later than their non-autistic peers. Interpretation: This study indicates that attention should be directed to motor abnormalities as well as sociability, communication, and restricted and repetitive behaviors in individuals with ASDs. Motor deficits add to children’s other handicaps. They indicate that ASDs affect a broader range of central nervous system circuitry than often appreciated.

Autism, Joint Hypermobility-Related Disorders and Pain

Autism Spectrum Disorder (ASD) and Joint Hypermobility-Related Disorders are blanket terms for two etiologically and clinically heterogeneous groups of pathologies that usually appears in childhood. These conditions are seen by different medical fields, such as psychiatry in the case of ASD, and musculoskeletal disciplines and genetics in the case of hypermobility-related disorders. Thus, a link between them is rarely established in clinical setting, despite a scarce but growing body of research suggesting that both conditions co-occur more often than expected by chance. Hypermobility is a frequent sign of hereditary disorders of connective tissue (e.g., Ehlers-Danlos syndromes, Marfan syndrome), in which the main characteristic is the multisystem fragility that prone to proprioceptive and motor coordination dysfunction and hence to trauma and chronic pain. Considering the high probability that pain remains disregarded and untreated in people with ASD due to communication and methodological difficulties, increasing awareness about the interconnection between ASD and hypermobility-related disorders is relevant, since it may help identify those ASD patients susceptible to chronic pain.

Autism and heritable bone fragility: A true association? (Osteogenesis Imperfecta + ASD)

Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an ‘Autism Spectrum Disorder’. A joint genetics and psychology research study was undertaken to identify these patients using ‘Gold Standard’ research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them.

Autism Spectrum Disorders and Ehlers-Danlos Syndrome Hypermobility-Type : Similarities in clinical presentation

Autism Spectrum Disorder (ASD) is an etiologically and clinically heterogeneous group of neurodevelopmental conditions, characterized by impairments in communication, social interac- tion and restricted repetitive and stereotyped behaviors. Ehlers-Danlos Syndrome hypermobility- type (EDS-HT; also known as Joint Hypermobility Syndrome), is the most common hereditary disorder of the connective tissue. It is characterized by joint hypermobility and a wide range of articular and non-articular manifestations, including disturbances in different systems due to the widespread distribution of collagen in the body. The clinical presentations of ASD and EDS-HT share several similar features, and although literature that relates these two conditions is scarce, it suggests that a connective tissue disorder may contribute to autistic symptomatology. The pre- sent work reviews the similarities in the clinical presentation of both conditions. In addition, the case of a 12-year-old boy diagnosed with ASD in which autistic manifestations overlap and/or might be explained by the presence of EDS-HT is presented as illustration.
Key

Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population

Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations.

Joint hypermobility and the heritable disorders of connective tissue: clinical and empirical evidence of links with psychiatry

The heritable disorders of connective tissue (HDCTs) are a group of genetic disorders affecting connective tissue matrix proteins. Fragility, laxity of tissues and joint hypermobility (JH) are commons features of HDCT for which the prognosis may range from benign to life threatening. JH and HDCTs, especially joint hypermobility syndrome, Ehlers–Danlos syndromes and Marfan syndrome, have been associated with psychiatric symptomatology. We explored the existing knowledge concerning this association in order to provide an overview of mental disorders linked to JH/HDCT, as well as the hypotheses proposed to explain such association. Results- Psychiatric conditions in which there is some evidence of an association with JH/HDCT are anxiety disorders, depression, schizophrenia, neurodevelopmental disorders (autism, attention deficit/hyperactivity disorder, and developmental coordination disorder), eating disorders, personality disorders and substance use/misuse.

Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers–Danlos syndrome or hypermobility syndrome and their siblings

Individuals with EDS and hypermobility syndrome are at increased risks of being diagnosed with psychiatric disorders. These risk increases may have a genetic and/or early environmental background as suggested by evidence showing that siblings to patients have elevated risks of certain psychiatric disorders.

Case Studies

Asperger's syndrome and ligamentous laxity.

Two autistic girls and one autistic man in whom Asperger's syndrome coexists with lifelong ligamentous laxity and muscular incoordination are described. Two had cranial circumferences at or above the 90th percentile as children, two have complex partial epilepsy, one has a colloid cyst of the third ventricle, and one had evidence of Sotos syndrome. Echocardiography was performed in the two girls and both had evidence of increased aortic compliance. It is suggested that all three suffer from a Marfan-like disorder of connective tissue and, more speculatively, that this has led to anomalous development of midline brain structures with consequent social handicaps characteristic of Asperger's syndrome.

 Concomitant neuropsychiatric symptoms in a case of Ehlers-Danlos syndrome

The case of a 15-year-old boy with Ehlers-Danlos-Syndrome (EDS) is described. Clinically the symptoms of considerable hyperextension of joints, abnormal extensibility of skin, moderate bleeding tendencies and slight vulnerability of the skin, deformity of the thorax are corresponding with type I of EDS. Ocular symptoms are missing. Histologically the picture is that of mitis type resp. type II of EDS. An autosomal dominant inheritance is to be supposed. Psychically an imbecillity likely as a result of perinatally acquired brain damage, and an autistic syndrome of broken home situation are present. Differential diagnosis and genetic significance of EDS are discussed.

Cornelia de Lange and Ehlers-Danlos: comorbidity of two rare syndromes

We present a case of a young adult with both Cornelia de Lange syndrome and Ehlers-Danlos syndrome. The patient showed non-verbal autism, intellectual disability and severe/intractable self-harming behaviours that led to a life-threatening complication (ie, septicaemia). A significant reduction in the self-harming behaviours was attained in a multidisciplinary neurobehavioural inpatient unit after addressing all causes of somatic pains, managing pain using level II and III analgesics, stabilising the patient's mood, limiting the iatrogenic effects of multiple prescriptions and offering a specific psychoeducational approach.

High‐functioning autistic disorder with Ehlers‐Danlos syndrome

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Related (But perhaps doesn't specifically talk about EDS/Connective Tissue Disorders + Autism specifically, or much)

A connective tissue disorder may underlie ESSENCE problems in childhood

Ehlers-Danlos syndrome hypermobility type, also known as Joint Hypermobility Syndrome (EDS-HT/JHS), is the most common hereditary disorder of the connective tissue (HDCT). It is characterized by tissue fragility, joint hypermobility and a wide range of articular and non-articular manifestations, which often appear in infancy. The clinical picture of EDS-HT/JHS is poorly known by the medical community, as is the presence of “ESSENCE” (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) problems in affected children. -- Children with EDS-HT/JHS present ESSENCE problems that often coexist and tend to be recognized before the HDCT. Clinicians encountering children with ESSENCE problems should consider the possibility of an underlying HDCT such as EDS-HT/JHS, probably influencing neurodevelopmental attributes in a subgroup of children. Awareness of these interconnected clinical problems might help improve early referral, diagnosis and treatment of EDS-HT/JHS.

Brain structure and joint hypermobility: Relevance to the expression of psychiatric symptoms

Joint hypermobility is overrepresented among people with anxiety and can be associated with abnormal autonomic reactivity. We tested for associations between regional cerebral grey matter and hypermobility in 72 healthy volunteers using voxel-based morphometry of structural brain scans. Strikingly, bilateral amygdala volume distinguished those with from those without hypermobility. The hypermobility group scored higher for interoceptive sensitivity yet were not significantly more anxious. Our findings specifically link hypermobility to the structural integrity of a brain centre implicated in normal and abnormal emotions and physiological responses. Our observations endorse hypermobility as a multisystem phenotype and suggest potential mechanisms mediating clinical vulnerability to neuropsychiatric symptoms.

Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives

In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers–Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. ©

Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised

Psychological distress is a known feature of generalized joint hypermobility (gJHM), as well as of its most common syndromic presentation, namely Ehlers–Danlos syndrome, hypermobility type (a.k.a. joint hypermobility syndrome — JHS/EDS‐HT), and significantly contributes to the quality of life of affected individuals. Most published articles dealt with the link between gJHM (or JHS/EDS‐HT) and anxiety‐related conditions, and a novel generation of studies is emerging aimed at investigating the psychopathologic background of such an association. In this paper, literature review was carried out with a semi‐systematic approach spanning the entire spectrum of psychopathological findings in gJHM and JHS/EDS‐HT. Interestingly, in addition to the confirmation of a tight link between anxiety and gJHM, preliminary connections with depression, attention deficit (and hyperactivity) disorder, autism spectrum disorders, and obsessive–compulsive personality disorder were also found. Few papers investigated the relationship with schizophrenia with contrasting results. The mind–body connections hypothesized on the basis of available data were discussed with focus on somatotype, presumed psychopathology, and involvement of the extracellular matrix in the central nervous system. The hypothesis of positive Beighton score and alteration of interoceptive/proprioceptive/body awareness as possible endophenotypes in families with symptomatic gJHM or JHS/EDS‐HT is also suggested. Concluding remarks addressed the implications of the psychopathological features of gJHM and JHS/EDS‐HT in clinical practice.