Understanding the Different Ehlers-Danlos Syndromes (EDS) and Their Connection to Autism Part 1
The EDS mascot.
Ehlers-Danlos Syndromes (EDS) are a group of heritable connective tissue disorders. They affect the collagen and extracellular matrix, which are fundamental to skin, joints, blood vessels, and internal organs. Collagen abnormalities can manifest across multiple body systems.
As of the 2017 International Classification, there are 13 recognized subtypes of EDS, each with a specific genetic cause (except for one). While not all forms are commonly associated with autism, several patterns in clinical and genetic overlap suggest emerging links between EDS—particularly hypermobile EDS (hEDS)—and autism spectrum disorder (ASD).
2. Classical EDS (cEDS)
Genes: COL5A1 or COL5A2 (affects type V collagen)
Inheritance: Autosomal dominant
Symptoms:
Severe skin hyperextensibility
Atrophic scars (“cigarette paper” scars)
Joint hypermobility (less than hEDS)
Easy bruising
Hernias
Muscle hypotonia
Delayed motor development
Foot deformities
Early-onset osteoarthritis
Autism Connection:
Some sensory-motor challenges overlap with autistic motor profiles
Hypotonia and delayed motor milestones may intersect with ASD-related motor delays
Rarely studied in autism research directly, but connective tissue fragility may complicate physical therapy for autistic individuals
1. Hypermobile EDS (hEDS)
Inheritance: Likely autosomal dominant; no confirmed gene yet
Symptoms:
Generalized joint hypermobility
Frequent joint dislocations or subluxations
Chronic musculoskeletal pain
Fatigue
Dysautonomia (especially POTS)
Gastrointestinal issues (IBS, GERD)
Soft or velvety skin
Easy bruising
Poor proprioception
Clumsiness or coordination difficulties
Anxiety and sensory sensitivities
Mast cell activation symptoms (flushing, rashes, allergic-type responses)
Autism Connection:
Most documented EDS-ASD comorbidity is seen in hEDS
Shared traits: sensory processing issues, proprioceptive dysfunction, anxiety, and fatigue
High rates of neurodivergence reported in EDS support groups and clinics
Likely overlap with hypermobility spectrum disorders (HSD), which may co-occur with ASD
4. Vascular EDS (vEDS)
Gene: COL3A1 (type III collagen)
Inheritance: Autosomal dominant
Symptoms:
Arterial, intestinal, or uterine rupture risk
Thin, translucent skin
Prominent veins
Easy bruising
Joint hypermobility (typically limited to small joints)
Characteristic facial features (thin nose, thin lips, small chin)
Autism Connection:
Minimal direct overlap
Because of medical fragility, autistic individuals with vEDS require extreme care during physical activity, restraint, or surgery
Anxiety and autonomic dysregulation may be compounded by comorbid ASD
3. Classical-like EDS (clEDS)
Gene: TNXB
Inheritance: Autosomal recessive
Symptoms:
Skin hyperextensibility without scarring
Joint hypermobility
Easy bruising
Muscle hypotonia
Autism Connection:
Largely unexplored in research
Muscle tone and joint instability may affect motor coordination in autistic individuals
TNXB mutations may impact extracellular matrix function relevant to neurodevelopment
6. Arthrochalasia EDS (aEDS)
Genes: COL1A1 or COL1A2
Inheritance: Autosomal dominant
Symptoms:
Congenital hip dislocation
Severe joint hypermobility
Skin hyperextensibility
Easy bruising
Hypotonia
Delayed gross motor milestones
Recurrent joint dislocations
Autism Connection:
High physical support needs may complicate early ASD identification
Motor delays can overlap with autistic motor planning issues
Physical therapy plans should be adjusted for joint instability and sensory needs
5. Kyphoscoliotic EDS (kEDS)
Genes: PLOD1 or FKBP14
Inheritance: Autosomal recessive
Symptoms:
Congenital muscle hypotonia
Progressive scoliosis (develops in infancy or early childhood)
Joint hypermobility
Skin fragility
Easy bruising
Abnormal scarring
Eye issues (e.g. scleral fragility, microcornea)
Autism Connection:
Hypotonia, coordination delays, and scoliosis also appear in subsets of autistic children
Sensory-motor integration difficulties may present more acutely when both conditions coexist
Requires multidisciplinary intervention planning
8. Musculocontractural EDS (mcEDS)
Genes: CHST14 or DSE
Inheritance: Autosomal recessive
Symptoms:
Congenital joint contractures
Craniofacial abnormalities
Hyperextensible, fragile skin
Recurrent dislocations
Clubfoot
Developmental delays
Vision and hearing problems
Autism Connection:
High prevalence of neurodevelopmental issues in some case studies
May be confused with autism if expressive communication and sensory integration are affected
Multisensory and motor planning supports recommended
7. Dermatosparaxis EDS (dEDS)
Gene: ADAMTS2
Inheritance: Autosomal recessive
Symptoms:
Extreme skin fragility
Sagging, soft, doughy skin
Bruising
Umbilical or inguinal hernias
Large fontanelles in infancy
Delayed motor development
Autism Connection:
Very rare; no confirmed associations yet
Physical vulnerabilities and motor delays could present similarly to ASD-related dyspraxia
Careful handling and sensory accommodations required
10. Periodontal EDS (pEDS)
Genes: C1R or C1S
Inheritance: Autosomal dominant
Symptoms:
Severe, early-onset gum disease
Early tooth loss
Joint hypermobility
Mild skin hyperextensibility
Easy bruising
Pretibial plaques
Autism Connection:
No established link
Oral sensitivity and dental anxiety are common in autism, and may be worsened by painful gum conditions
Requires trauma-informed dental care
9. Myopathic EDS (mEDS)
Genes: COL12A1
Inheritance: Autosomal dominant or recessive
Symptoms:
Congenital muscle hypotonia
Delayed motor milestones
Joint hypermobility
Proximal joint contractures
Mild skin involvement
Autism Connection:
Muscle tone and movement differences may resemble autistic motor profiles
May co-occur with sensory sensitivities and require orthotic or adaptive supports
Important to rule out dual diagnosis when developmental delays appear
12. Spondylodysplastic EDS (spEDS)
Genes: B4GALT7, B3GALT6, SLC39A13
Inheritance: Autosomal recessive
Symptoms:
Short stature
Muscle hypotonia
Bowing of limbs
Delayed motor development
Joint laxity
Spinal deformities
Autism Connection:
Some children with spEDS present with developmental delays
Important to differentiate between physical, cognitive, and social development delays
May co-occur with neurodevelopmental conditions including autism
11. Brittle Cornea Syndrome (BCS)
Genes: ZNF469 or PRDM5
Inheritance: Autosomal recessive
Symptoms:
Thin, fragile corneas (risk of rupture)
Severe myopia
Keratoconus
Hearing loss
Joint hypermobility
Skin fragility
Autism Connection:
No direct connection noted
Requires vision and hearing supports—important to distinguish from ASD-related sensory differences
Overlap possible in cases of sensory aversion or adaptive communication needs
13. Cardiac-Valvular EDS (cvEDS)
Gene: COL1A2 (biallelic mutations)
Inheritance: Autosomal recessive
Symptoms:
Severe heart valve disease
Skin hyperextensibility
Joint hypermobility
Easy bruising
Flat feet
Autism Connection:
No direct correlation
Cardiac monitoring is crucial during any medical procedure, including for autistic individuals with co-occurring sensory issues or movement disorders