A diagnosis of autism is often followed, or preceded by, other diagnosis. Many conditions mimic autism and vice versa. Some increase the risk for autism, some are common comorbid conditions with autism.
Some children diagnosed with autism spectrum disorders are also diagnosed with Ehlers Danlos syndrome. Today I want to discuss Ehlers Danlos and autism, and how they relate to each other.
What is Ehlers-Danlos Syndrome?
According to the Mayo Clinic, ehlers danlos syndrome is “a group of inherited disorders that affect your connective tissues — primarily your skin, joints and blood vessel walls. Connective tissue is a complex mixture of proteins and other substances that provide strength and elasticity to the underlying structures in your body.”
EDS shares symptoms with other hypermobility related disorders such as:
- Joint hypermobility related disorders
- generalized hypermobility spectrum disorders
- hereditary connective tissue disorders
- joint hypermobility syndrome
- joint hypermobility spectrum disorders
- generalized joint hypermobility spectrum disorders
The National Health Service (NHS) in the UK explains there are 13 types of EDS, most of which are very rare.
Hypermobile EDS (hEDS) is the most common type. Other types of EDS include classical EDS, vascular EDS, kyphoscoliotic EDS, and others.
Hypermobile EDS
People with hEDS may have:
- joint hypermobility
- loose, unstable joints that dislocate easily
- joint pain and clicking joints
- extreme tiredness (fatigue)
- skin that bruises easily
- digestive problems, such as heartburn and constipation
- dizziness and an increased heart rate after standing up
- problems with internal organs, such as mitral valve prolapse or organ prolapse
- problems with bladder control (stress incontinence)
Currently, there are no tests to confirm whether someone has hEDS.
The diagnosis is made based on a person’s medical history and a physical examination.
Classical EDS
Classical EDS (cEDS) is less common than hypermobile EDS and tends to affect the skin more.
People with cEDS may have:
- joint hypermobility
- loose, unstable joints that dislocate easily
- stretchy skin
- fragile skin that can split easily, especially over the forehead, knees, shins and elbows
- smooth, velvety skin that bruises easily
- wounds that are slow to heal and leave wide scars
- hernias and organ prolapse
Vascular EDS
Vascular EDS (vEDS) is a rare type of EDS and is often considered to be the most “serious”.
It affects the blood vessels and internal organs, which can cause them to split open and lead to life-threatening bleeding.
People with vEDS may have:
- skin that bruises very easily
- thin skin with visible small blood vessels, particularly on the upper chest and legs
- fragile blood vessels that can bulge or tear, resulting in serious internal bleeding
- a risk of organ problems, such as the bowel tearing, the womb tearing (in late pregnancy) and partial collapse of the lung
- hypermobile fingers and toes, unusual facial features (such as a thin nose and lips, large eyes and small earlobes), varicose veins, and delayed wound healing
Kyphoscoliotic EDS
Kyphoscoliotic EDS (kEDS) is rare.
People with kEDS may have:
- curvature of the spine – this starts in early childhood and often gets worse in the teenage years
- joint hypermobility
- loose, unstable joints that dislocate easily
- weak muscle tone from childhood (hypotonia) – this may cause a delay in sitting and walking, or difficulty walking if symptoms get worse
- fragile eyes that can easily be damaged
- soft, velvety skin that is stretchy, bruises easily, and scars
How is EDS diagnosed?
Like many other conditions, EDS is diagnosed using a specific set of criteria. The criteria are outlined in book called Gene Reviews: Hypermobile Ehlers-Danlos Syndrome as follows:
“The diagnostic criteria for hEDS (and all other types of EDS) were revised by the International EDS Consortium in 2017 [Malfait et al 2017]. No underlying genetic etiology has yet been identified in hEDS, and thus the diagnosis is based entirely on clinical evaluation and family history.
“Joint hypermobility is a feature of many heritable and acquired disorders (see Differential Diagnosis), and may also occur as an asymptomatic and/or nonsyndromic finding. In order to reduce heterogeneity and enhance efforts to identify the genetic etiology, a formal diagnosis of hEDS should be made only when all of the diagnostic criteria are met. Individuals with signs and symptoms suggestive of a hereditary connective tissue disorder who fail to meet diagnostic criteria for hEDS or any other described condition should be considered to have hypermobility spectrum disorder (HSD) [Castori et al 2017].
“The clinical diagnosis of hEDS requires the simultaneous presence of three criteria:
- Generalized joint hypermobility (Criterion 1)
- Evidence of syndromic features, musculoskeletal complications, and/or family history (Criterion 2)
- Exclusion of alternative diagnoses (Criterion 3)
“Multiple other clinical features including (but not limited to) sleep disturbance, fatigue, postural orthostatic tachycardia, functional gastrointestinal disorders, dysautonomia, anxiety, and depression are associated with hEDS. Some of these features were formerly included as minor diagnostic criteria for hEDS [Beighton et al 1998]. They were excluded from the 2017 hEDS diagnostic criteria because they lack specificity for hEDS [Malfait et al 2017].”
What are the symptoms of EDS?
We learn from the Mayo Clinic, that common symptoms of EDS can include:
- Overly flexible joints. Because the connective tissue that holds joints together is looser, your joints can move far past the normal range of motion. Joint pain and dislocations are common
- Stretchy skin. Weakened connective tissue allows your skin to stretch much more than usual. You may be able to pull a pinch of skin up away from your flesh, but it will snap right back into place when you let go. Your skin might also feel exceptionally soft and velvety
- Fragile skin. Damaged skin often doesn’t heal well. For example, the stitches used to close a wound often will tear out and leave a gaping scar. These scars may look thin and crinkly.
What is the connection between autism and Ehlers Danlos?
Autism spectrum disorders and EDS both share various connections. Some of them include symptom overlap, and comorbid conditions.
A study called The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders concluded:
“Although autism is defined neurobehaviorally and EDS/HSD by various articular and extra-articular connective tissue manifestations, these two conditions share considerable phenotypic overlap at various levels. Genetic data indicate similarities at the molecular, cellular, and tissue levels, as illustrated by numerous genetic syndromes with comorbid autism and hypermobility, which we have reviewed within this manuscript. EDS/HSD and autism comorbidity and familial co-occurrence lend further credence to this relationship, suggesting potential links via the maternal immune system
“Meanwhile, these two spectrum conditions share a variety of secondary comorbidities, including similar neurobehavioral, psychiatric, and neurological phenotypes, such as ADHD, anxiety and mood disorders, proprioceptive impairment, sensory hyper-/hyposensitivities, eating disorders, suicidality, epilepsy, structural abnormalities such as Chiari I malformation and periventricular heterotopias, and sleep disorders—particularly those involving SDB. Relevant to these neurophenotypes are also common autonomic disorders (sympathetic hyperarousal, low parasympathetic tone) and immune disorders, which may influence cognition (e.g., anxiety, depression, fatigue, sleep disorders).”
Symptom overlap
In the same study we learn: “Although the criteria of these two complex spectrum conditions appear different on paper (one is defined by neurobehavioral symptomology, while the other is defined by structural manifestations of connective tissue impairment), they share not only comorbidity and familial co-occurrence but symptom overlap.”
Shared symptoms encompass the nervous system and immune dysregulation.
Attention deficit hyperactivity disorder
“Neurodevelopmental issues in EDS/HSD may also be related to proprioceptive impairment, which alters coordination and posture, and likewise may be involved in the acquisition of verbal communication and motor competence [52]. Baeza Velasco, C et al. [28,48] have proposed that in order to maintain motor competence despite proprioceptive impairment, executive function may be overwhelmed in those affected, leading to some symptoms reminiscent of ADHD.”
Neuropsychiatric symptoms and psychiatric disorders
“Other psychiatric features that are common in both autism and EDS/HSD include: anxiety, depression, bipolar disorder, eating disorders, and suicidal behaviors…”
Other conditions that can present in ASD and EDS may include:
- learning disorders
- developmental coordination disorders
- hypermobility related disorders
- neurodevelopmental disorders
- immune disorders
- chronic pain
There is also evidence to suggest that having EDS or autism spectrum disorders may make it more likely a person may develop other conditions. One of those conditions is epilepsy.
“In autism, for instance, the lifetime risk for developing epilepsy ranges between 2.7% to 44.4%, which is a seven-fold increased risk compared to the general population. Individuals with intellectual disability experience the highest rates of epilepsy at approximately 22%; however, autistic people without intellectual disability still develop epilepsy at a rate of about 8% as compared to 0.75–1.1% within the general population. In addition, abnormal electroencephalograms (EEG), even in the absence of epilepsy, have been reported in up to 60% of those with autism.
Seizure disorders have also been reported in EDS/HSD, particularly in association with certain subtypes such as an EDS-like disorder associated with mutations in the FLNA gene.”
How do you get EDS?
EDS are a group of hereditary connective tissue disorders. This means that they are passed down from parents to their children. Although rare cases have been reported of spontaneous instances of EDS, the majority are heritable disorders.
Genetic counseling can help in the quest for whether or not someone would be at risk. Genetic counseling would begin with a proband: a person serving as the starting point for the genetic study.
In the aforementioned book we learn the risk to family members for EDS.
Risk to family members
Parents of a proband
“Most individuals diagnosed with hEDS have an affected parent, although a careful history and examination of the parents is often necessary to recognize that, despite absence of serious complications, one and sometimes both parents have current or prior history of joint laxity, easy bruising, and soft skin.
- A proband with hEDS may have the disorder as the result of a de novo pathogenic variant. The proportion of cases caused by a de novo pathogenic variant is unknown
- Recommendations for the evaluation of parents of a proband with an apparent de novo pathogenic variant include a careful history and physical examination seeking current or prior history of joint laxity, easy bruising, and soft skin
- Although most individuals diagnosed with hEDS have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members
“Sibs of a proband. The risk to the sibs (siblings) of the proband depends on the genetic status of the proband’s parents:
- If a parent of the proband is affected, the risk to the sibs is 50%
- When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low
“Offspring of a proband. Each child of an individual with hEDS has a 50% chance of inheriting the same pathogenic variant (and thus the same type of EDS). However, because of marked clinical variability, it is difficult to predict severity among affected offspring.
“Other family members. The risk to other family members depends on the genetic status of the proband’s parents: if a parent is affected, his or her family members may be at risk.”
Is there a cure for EDS?
The National Health Service says: “There’s no specific treatment for EDS, but it’s possible to manage many of the symptoms with support and advice.
People with EDS may also benefit from support from a number of different healthcare professionals.
For example:
- a physiotherapist can teach you exercises to help strengthen your joints, avoid injuries and manage pain
- an occupational therapist can help you manage daily activities and give advice on equipment that may help you
- counseling and cognitive behavioral therapy (CBT) may be useful if you’re struggling to cope with long-term pain
- for certain types of EDS, regular scans carried out in hospital can detect problems with internal organs
- genetic counseling can help you learn more about the cause of your condition, how it’s inherited, and what the risks are of passing it on to your children
Your GP or consultant can refer you to these services.”
Conclusion
Autism spectrum disorder and connective tissue disorders do co-occur. With the overlap of symptoms, there are times when EDS and autism can mimic each other. Though they are two very different conditions, they do have much in common.
Both conditions often require the same therapies and treatments as patients deal with physical impairment, mental health issues, chronic pain, and mobility struggles. Each carries risks of also being diagnosed with the other.
There is also evidence showing that EDS could worsen autism spectrum disorder symptoms as well. Therefore, a child with autism, who presents symptoms consistent with EDS should be considered for diagnosis and treatment.
Further scientific interest and study is needed to learn more about these conditions, and help the remarkable patient group who have both autism spectrum disorder and Ehlers danlos syndrome.
If your child is struggling, speak with their pediatrician, they can help guide you to get the help your family needs. Also, don’t forget to take some time to invest in your own health. There are therapies and support available for parents as well.
References:
Levy HP. Hypermobile Ehlers-Danlos Syndrome. 2004 Oct 22 [Updated 2018 Jun 21]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1279/
Casanova, E. L., Baeza-Velasco, C., Buchanan, C. B., & Casanova, M. F. (2020). The Relationship between Autism and Ehlers-Danlos Syndromes/Hypermobility Spectrum Disorders. Journal of personalized medicine, 10(4), 260. https://doi.org/10.3390/jpm10040260
