What is the diagnosis for a patient with a 5-year history of left hand paresthesias, right eye mild color oversaturation, mild clicking in the throat with swallowing, joint cracking in the left ankle, hip, shoulder, and wrist, easy bruising, nail splinter hemorrhages, and worsening left-sided musculature fatigue, despite normal eye workup, brain and cervical MRI, EMG, barium swallow, and ENT nasal to throat scope, with recent worsening of hip clicking and increased size of the cisterna magna?

Diagnostic Consideration: Connective Tissue Disorder with Neurovascular Manifestations

This constellation of symptoms—progressive left-sided paresthesias and muscle fatigue, joint hypermobility with clicking, splinter hemorrhages, easy bruising, dysphagia, and visual color oversaturation—most strongly suggests a connective tissue disorder, likely Ehlers-Danlos syndrome (EDS) with associated neurovascular complications, though functional neurological disorder and myasthenia gravis warrant consideration given the pattern of fluctuating symptoms.

Key Diagnostic Features Supporting Connective Tissue Disorder

Vascular and Dermatologic Signs

• Splinter hemorrhages and easy bruising are classic external examination findings that suggest underlying connective tissue fragility 1
• These findings, combined with joint manifestations, point toward a systemic disorder affecting collagen structure rather than isolated neurological pathology 1

Joint Manifestations

• Unilateral joint clicking across multiple sites (ankle, hip, shoulder, wrist) with recent acute worsening suggests joint hypermobility or ligamentous laxity 1
• The progressive nature over years, rather than acute onset, distinguishes this from traumatic or inflammatory arthropathy 2

Neurological Pattern

• The combination of left-sided paresthesias, progressive muscle fatigue (especially triceps), and normal EMG at 4 years suggests a non-myopathic, non-neuropathic process 3
• The stability of symptoms over 5 years with gradual progression argues against acute demyelinating disease or stroke 4
• Normal brain and cervical MRI studies (except enlarged cisterna magna) effectively exclude structural lesions, demyelination, and acute vascular events 1

Bulbar Symptoms

• Throat clicking with swallowing progressing to dysphagia, despite normal barium swallow and ENT scope, suggests functional or structural pharyngeal/laryngeal instability 1
• This pattern can occur with craniocervical instability seen in connective tissue disorders 1

Visual Symptoms

• Mild color oversaturation in one eye with normal visual acuity and comprehensive eye workup suggests a subtle optic nerve or retinal issue not detected by standard testing 1
• The stability over 5 years makes progressive optic neuropathy or retinal vascular occlusion unlikely 1

Critical Differential Diagnoses to Exclude

Myasthenia Gravis

• Variable weakness with fatigue, dysphagia, and diplopia are hallmarks, but the normal EMG at 4 years makes this diagnosis less likely 1
• The ice pack test and acetylcholine receptor antibody testing should be performed if not already done, as EMG can be falsely negative in 10% of ocular myasthenia cases 1
• The unilateral nature of symptoms and lack of ptosis or diplopia make myasthenia less probable 1

Functional Neurological Disorder

• The presence of multiple inconsistent symptoms across different body systems, normal extensive workup, and chronicity could suggest functional disorder 1, 5
• However, the physical signs of splinter hemorrhages, easy bruising, and joint clicking provide objective findings that argue against purely functional etiology 1
• Functional disorders typically show internal inconsistency—symptoms that resolve with distraction or vary unpredictably—which should be assessed during examination 1

Neuromuscular Disorder

• Progressive unilateral muscle fatigue with normal EMG makes primary myopathy or motor neuron disease unlikely 3
• If creatine kinase has not been checked, this should be done urgently, as elevated CK >10× upper limit of normal would necessitate immediate evaluation for rhabdomyolysis 3

Recommended Diagnostic Workup

Immediate Priority Testing

• Genetic testing for Ehlers-Danlos syndrome subtypes, particularly vascular EDS (type IV), given the splinter hemorrhages and easy bruising 3
• Echocardiogram to evaluate for mitral valve prolapse and aortic root dilation, common in connective tissue disorders 1
• Creatine kinase level to exclude occult myopathy 3

Specialized Neurovascular Assessment

• MRI/MRA of the craniocervical junction with flexion-extension views to assess for atlantoaxial instability or craniocervical settling, which can cause unilateral symptoms and dysphagia 4
• The enlarged cisterna magna may be a normal variant but could also indicate posterior fossa crowding or Chiari malformation 4
• Formal autonomic testing if orthostatic symptoms or dysautonomia are present, as these commonly accompany EDS 2

Ophthalmologic Re-evaluation

• Optical coherence tomography (OCT) of the retina and optic nerve to detect subtle structural changes not visible on standard examination 1
• Visual evoked potentials to assess optic nerve function objectively 1

Myasthenia Gravis Exclusion

• Acetylcholine receptor antibodies (binding, blocking, and modulating), anti-MuSK antibodies, and anti-LRP4 antibodies 1
• Ice pack test: apply ice over closed eyes for 2 minutes and reassess for improvement in ptosis or 5 minutes for improvement in ocular alignment 1
• Single-fiber EMG is the gold standard with >90% sensitivity for ocular myasthenia if standard EMG was normal 1

Management Approach

If Connective Tissue Disorder Confirmed

• Referral to medical genetics and rheumatology for comprehensive evaluation and management 3
• Physical therapy focusing on joint stabilization exercises, avoiding hypermobility-inducing activities 4
• Cardiovascular monitoring given vascular fragility risk 1
• Genetic counseling regarding inheritance patterns and family screening 3

If Myasthenia Gravis Confirmed

• Pyridostigmine bromide 2-4 times daily as first-line treatment, though only 50% of patients with strabismus-associated myasthenia respond 1
• Corticosteroids show positive response in 66-85% of patients 1
• Referral to neurology for immunosuppressive therapy consideration 1

If Functional Neurological Disorder Suspected

• Positive diagnosis explanation emphasizing that symptoms are real but reflect altered nervous system function rather than structural damage 1
• Referral to speech-language pathology for dysphagia management using behavioral interventions 1
• Physical therapy with focus on retraining normal movement patterns 1, 4

Critical Pitfalls to Avoid

• Never assume stable symptoms over years represent a benign process—connective tissue disorders can have life-threatening vascular complications 1, 3
• Do not dismiss splinter hemorrhages and easy bruising as insignificant; these are objective signs requiring systemic evaluation 1
• Avoid attributing all symptoms to functional disorder when objective physical findings are present 1, 5
• Do not delay genetic testing in favor of repeated neuroimaging when clinical pattern suggests hereditary connective tissue disorder 3
• Never assume normal standard EMG excludes myasthenia gravis—single-fiber EMG is required for definitive exclusion 1
• Recognize that multiple normal tests do not equal "nothing wrong"—they narrow the differential toward systemic disorders not detected by standard neuroimaging 6, 2