What are the common symptoms of a patient with a rare connective tissue disorder?

Common Symptoms of Rare Connective Tissue Disorders

Patients with rare connective tissue disorders most commonly present with joint hypermobility and arthralgias (85% of cases), Raynaud's phenomenon, progressive dyspnea, and characteristic skin manifestations including hyperextensibility or thickening, with symptoms often appearing insidiously over months before diagnosis. 1, 2

Musculoskeletal Manifestations

• Joint-related symptoms are the most frequent presenting complaint, with arthralgias occurring in 85% of patients and swollen joints being a cardinal feature 1, 2
• Ligamentous laxity and joint hypermobility constitute the cardinal feature of the majority of these disorders, with joints showing increased range of movement 3
• Articular effusions and increased risk of joint or soft tissue injury occur due to the underlying connective tissue weakness 3
• Musculoskeletal pain and weakness are common complaints that should be carefully elicited, along with morning stiffness 4

Vascular and Raynaud's Phenomenon

• Raynaud's phenomenon is one of the most common clinical manifestations, particularly in mixed connective tissue disease and systemic sclerosis 4, 1
• Digital manifestations include swollen hands and fingers with sausage-like appearance 1
• Photosensitivity may be present in certain subtypes 4

Respiratory Symptoms

• Progressive dyspnea on exertion is the most prominent and disabling symptom when interstitial lung disease develops, typically present for >6 months before presentation 4
• Nonproductive cough occurs in 40-50% of patients and may be paroxysmal, dry, and refractory to antitussive agents 4
• Fatigue, cough, or dyspnea on exertion are nonspecific symptoms that may hide behind other organ involvement or associated comorbidities like myopathy or cardiac disease 4
• Early but irreversible lung function loss can occur asymptomatically, making respiratory symptoms particularly concerning 4

Dermatologic Features

• Skin hyperextensibility, tissue fragility, and abnormal scarring form a characteristic triad in Ehlers-Danlos syndromes 3
• Dry skin, eczema, and dystrophic nails with rapid nail growth are common 4
• Sparse or abnormal hair growth including wavy or curly scalp hair with sparse hair at temples, and sparse eyebrows (only 10% have normal eyebrows) 4
• Hyperpigmentation and numerous acquired melanocytic nevi are striking features, with individuals potentially developing over 100 nevi as they age 4
• Keratosis pilaris (follicular hyperkeratosis of extremities and/or face) is seen in the majority of cases 4

Gastrointestinal Symptoms

• Esophageal dysfunction is a common manifestation, particularly in mixed connective tissue disease 1
• Weight loss, malaise, and fatigue may be noted, though fever is rare and suggests an alternative diagnosis 4

Cardiovascular Manifestations

• Cardiac abnormalities including mitral valve prolapse, mitral regurgitation, and arrhythmias occur in certain subtypes like Marfan syndrome 3
• Hypertrophic cardiomyopathy can occur in nearly 40% of individuals with cardio-facio-cutaneous syndrome, sometimes rapidly progressive and even resulting in death 4

Neurological and Cognitive Features

• Intellectual disability is present in 90-100% of individuals with certain rare subtypes like cardio-facio-cutaneous syndrome 4
• Seizures may occur and are often refractory to medications, requiring multiple anticonvulsants 4
• Gross motor delays tend to be more pronounced in early years, with mean age of independent walking around 3 years in affected individuals 4

Ocular Manifestations

• Myopia and astigmatism are common in Marfan syndrome 3
• Blue sclera is a cardinal feature of osteogenesis imperfecta 3
• Dry eyes should be carefully elicited as part of Sjögren's overlap features 4

Physical Examination Findings

• "Velcro" crackles on chest auscultation are detected in >80% of patients with interstitial lung disease, typically dry, end-inspiratory, and most prevalent in lung bases 4
• Clubbing is noted in 25-50% of patients with progressive pulmonary involvement 4
• Tall stature with low upper:lower segment ratio and arm span greater than height in Marfan syndrome 3
• Pectus deformity and scoliosis are skeletal characteristics of certain subtypes 3

Critical Pitfall to Avoid

Do not dismiss nonspecific symptoms like fatigue, mild dyspnea, or arthralgias as benign, as early but irreversible organ damage (particularly lung fibrosis) can occur asymptomatically in the first 5-7 years after disease onset, and maintaining high clinical suspicion for interstitial lung disease is essential even when systemic symptoms appear mild. 4