Hypermobility (and a little on inherited collagen disorders) Anna moverley Consultant rheumatologist

Joint hypermobility Important cause of widespread and diffuse chronic pain If able to move beyond normal joint range, ability to overstretch can cause pain to occur Global approach essential, with physiotherapy input Joint stabilizing exercises Core strength Proprioception training Overuse injury prevention – managing activities

Benign joint hypermobility syndrome Beighton criteria Thumb to wrist (2) Dorsiflexion of little finger >90 (2) Hyperextend elbows (2) Hyperextend knees (2) Hands flat on floor without bending knees (1) 4 plus = hypermobility Remember joint laxity decreases with age – ask about childhood activities esp. dance and gymnastics

How to manage hypermobility Reassurance Physiotherapy Simple analgesia Consider screening for cardiac and ophthalmological complications if features of concern

Collagen disorders Collagen and fibrillin are major connective tissue proteins with important mechanical functions There are a number of types of collagen and a number of gene mutations leading to many subtypes of collagen disease Inherited collagen disorders may be suspected if systemic features are present in addition to hypermobility

Osteogenesis imperfecta ‘Brittle bone disease’ Spectrum of conditions from asymptomatic to stillbirth Abnormalities of type I collagen found in bone, but also ligaments, teeth, sclera and skin Ligamental laxity, joint hypermobility, easy bruising and poor dentition are common Osteopenia, deformity and fractures are common as well (clinically and radiographically)

Osteogenesis imperfecta Type Clinical features Inheritance Defect I Normal bone growth/dentition Hearing loss in 50% Blue sclera AD Decreased production type I procollagen II Lethal - stillbirths AD/AR (rare) Rearrangement collagen gIA/IIA III Deformed growth at birth, worsens Poor dentition/hearing loss common AD/AR Mutations alpha 1 alpha 2 collagen chains IV Often bone deformity and short stature Poor dentition No hearing loss Normal sclerae Mutations in alpha 2 chains

Marfan syndrome Characterised by Long extremities (span/height ratio > 1.03) Long fingers and feet (arachnodactyly) Tall stature (upper segment/lower segment ratio < 0.89) Pectus deformity of chest wall High arched palate Mandibular hypoplasia Lens dislocation and myopia Joint laxity

Marfan syndrome Autosomal dominant with complete penetrance Prevalence 1:25,000 Numerous gene mutations, linked to abnormalities of protein fibrillin types I and II Predisposition to mitral valve prolapse and acute aortic valve rupture – need CT/MR plus echo Subgroup without vascular abnormalities exists – congenital contractual arachnodactyly

Ehlers-Danlos syndrome Again, a heterogeneous condition, clinical diagnosis Skin fragility, joint laxity, short stature, spinal deformity, vascular fragility and, rarely, retinal detachment At least 9 genetic subtypes, with defined biochemical abnormalities detected in at least 5 Inheritance patterns variable (AD, AR, X-linked)

Ehlers-Danlos syndrome Vascular (type IV) EDS patients have characteristic faces ( wide spaced eyes, lobe-less ears) Prone to vascular rupture - even in the absence of documented aneurysms – sudden death Watch out also for pregnancy (cervical incompetence, spontaneous abortion, early birth, tissue trauma), post-partum (moving and stretching) and surgery (skin fragility)

Systemic features to look out for Musculoskeletal: Pain in two or more limbs daily, or widespread pain for >3mths Recurrent joint dislocations in the absence of trauma; 3 or more at the same site or in 2 different joints at 2 different times; medical diagnosis of >2 unstable joints without trauma Dermatological: Abnormal elasticity Unexplained striae Atrophic scarring > 1 site or classic tissue paper, haemosiderin

Ophthalmological: Mucosal: Cardiac: Lens dislocation Myopia Dental crowding AND high or narrow palate Cardiac: Mitral valve prolapse Aortic root dilatation Autonomic symptoms (hypotension, syncope, tachycardia)

Connective tissue weaknesses Recurrent or multiple abdominal hernia Pelvic floor, rectal or uterine prolapse in men, children or nulliparous women without other predisposing condition Abnormal body habitus Arm span to height ratio 1.05 or more and/or upper segment to lower segment ratio < 0.89; arachnodactyly Family history 1st or 2nd degree relative with inherited collagen disorder

When to consider referral to secondary care, and what information to include Beighton criteria confirmation of hypermobility, plus more than one systemic feature Other concerns can be managed through advice and guidance requests Include Beighton score, history of recurrent joint dislocation, and any systemic symptoms of concern related to inherited disorders of connective tissues

Sheffield Genetic Diagnostic Service Genetics service, not a clinical consultation Hypermobile patients are often aware of this service Useful to confirm/refute diagnosis in what can be a difficult situation to manage