Triad, Pentad & Beyond

Neurodevelopmental Conditions:

• ADHD: Common with generalized joint hypermobility (GJH), motor challenges, and EDS.

• Autism Spectrum Disorder (ASD): Linked to hypermobility; hypermobile autistic people often report higher rates of autoimmunity and chronic pain.

• Developmental Coordination Disorder (DCD): Impaired coordination and proprioception, often overlapping with ADHD and GJH.

• Concepts like DAMP (Deficit in Attention, Motor Control and Perception) and ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) help describe these clusters.

Pain Syndromes & Fatigue:

• Fibromyalgia (FM): Chronic widespread pain and central sensitization, frequent in GJH and dysautonomia.

• Chronic Fatigue Syndrome (CFS) / Myalgic Encephalomyelitis (ME): Severe fatigue and post-exertional malaise, with inflammation links and overlap with MCAS.

• Small Fiber Polyneuropathy (SFP): Nerve damage causing widespread pain and GI issues, common in hypermobile EDS.

• Long COVID: GJH is a risk factor for prolonged symptoms and fatigue.

Central Nervous System (CNS) Complications:

• Cranio-Cervical Instability (CCI): Skull-neck instability, brainstem compression, headaches, dizziness.

• Tethered Cord Syndrome: Restricted spinal cord movement, causing bladder issues, weakness, and back pain.

• Chiari Malformation Type 1: Brain tissue crowding the spinal canal, linked to intracranial pressure issues.

• Intracranial Pressure Dysregulation: Includes idiopathic intracranial hypertension (high pressure) or spontaneous intracranial hypotension (low pressure).

Vascular Abdominal Pathologies (“Syndromes of Sag”):

• SMA Syndrome: Duodenum compression.

• Nutcracker Syndrome: Left renal vein compression.

• May-Thurner Syndrome: Left common iliac vein compression.

These contribute to blood pooling and worsen POTS symptoms.

Mental Health & Cognitive Issues:

• Anxiety & Panic Disorders: Strongly associated with GJH and changes in brain structure.

• Depression: Higher rates seen in hypermobility and EDS, suggesting genetic or biological overlap.

• Other Psychiatric Disorders: Bipolar disorder and higher suicide risk have been noted.

• Brain Fog: Common with POTS, ME/CFS, and hypermobility — tied to dysautonomia and inflammation.

Other Common Issues:

• Chronic Pain: Widespread pain, headaches, nociplastic / nociceptive and neuropathic pain.

• Sleep Disorders: Insomnia, obstructive/central sleep apnea linked to nervous system dysregulation.

• Endocrine Disorders: Hormone-sensitive gynecological issues are often reported.

Key Takeaway: Understanding the Triad, Pentad, and related conditions empowers patients and providers to see the big picture and manage multi-system symptoms with an integrated plan.