Genetic Skeletal Dysplasias, Juvenile Idiopathic Arthritis and Legg-Calve-Perthe Disease

Question 1

What are genetic skeletal dysplasia?

Answer 1

Genetic disorders of skeletal development at birth, subdivided into chrondroplasias (i.e. achondroplasia) and osteodysplasia (i.e. osteogenesis imperfecta

Question 2

What is the chondriocyte aetiology of GSD?

Answer 2

Chondrodysplasia: mutations in genes affecting cartilage matrix proteins, transmembrane receptors, TF and ion transporters

o Achondroplasia: AD condition involving mutation in FGFR3 gene on CHr4. 50% de novo. Increased FGFR3 gene function leading to reduced endochondrial ossification.

Question 3

What is the osteocyte aetiology of GSD?

Answer 3

Osteodysplasia: mutations in genes for bone development.

o Osteogenesis imperfecta: AD mutation for Type I collagen. Substitution of glycine residues in the normal glycine-X-Y alternation sequence.

Question 4

What is the epidemiology of the different aetiologies of GSD?

Answer 4

ACD: 1/10k py.

OI: 1/20k py.

Question 5

What would you find the history or exam of someone with achondroplasia?

Answer 5

Average trunk length, short limbs, megalocephaly, short stature, angular deformity of extremities. Cervicomedullary compression may be present (ataxia, pain, aopnea, incontinence).

Question 6

What are the types of osteogenesis imperfecta?

Answer 6

· Type I recurrent fractures and blue sclera, early deafness.

· Type II: most severe, may be stillborn or die in infancy from respiratory insufficiency. Fragile, low BW, small thorax.

· Type III: in utero fractures, macrocephaly, triangular facies, scoliosis.

· Type IV: moderate short stature, bowing of legs, often mobile.

Question 7

What investigations would you do for ACD?

Answer 7

· Radiology: large skull cap vones, small cranial base and facial bones.

· MRI spine for cervical stenosis

Question 8

What investigations would you do for OI?

Answer 8

· DEXA: BMD<75% normal

· Lumbar SXR: for cmpresson from fractures.

· Collagen synthesis analysis

Question 9

What is the management for the two types of GSD?

Answer 9

ACD: Gh/IGF, neuro follow up, surgical decompresion of cervical stenosis, leg lengthening.

OI: prompt fracture splinting or casting to restore function, physiotherapy in young children, mobility aid.

Question 10

What are the complications of ACD and OI?

Answer 10

ACD: CVJ deformities leading to spinal comrpession, quadripareisis and respiratory arrest.

OI: recurrent pneumonia, brainstem compresison, hydrocephalys, syringohydromyelia.

Question 11

What is the prognosis of ACD and OI?

Answer 11

AD: normal lifespan and intelligence

OI: Type I/IV associated with normal lifespan, Type III respiratory problems, Type II die in infancy.

Question 12

What is juvenile idiopathic arthritis?

Answer 12

Group of chronic arthropathies in childhood.

Question 13

What are the 7 ILAR subtypes?

Answer 13

1. Systemic: sJIA: >1j, preceded by fever>3d with rash, lymphadenopathy etc.
2. Oligoarticular : <4 joints, may be persistent or extended.
3. Polyarticular, RF negative
4. Polyarticular, RF positive
5. Enthesitis-related arthritis ERA: arthritis and enthesitis, sacroiliac/lumbosacral pain, HLAB27, male>6y, acure anterior uveitis, Reiter syndrome (reactive arthritis following GI or STI infection)
6. Psoriatic arthritis: With psoriasis
7. Undifferentiated: No category or more than 2 of the baove

Question 14

What is the aetiology and Ddx for juvenile idiopathic arthitis?

Answer 14

Aberrant immune or inflammatory response leading to T cell activation, humoral immunity or innate immunity initiation. HAL subtypes linked to risk.

DDx: Bacterial/viral infection, malignancy, vasculitis, CT disease. Septic arthritis if single joint.

Question 15

What is the epidemiology of Juvenile idiopathic arthritis?

Answer 15

Most common rheumatic disease in children. 150/100k. sJIA mostly (10%).

Question 16

What is the history/ exam of someone with Juvenile idiopathic arthritis?

Answer 16

General: acute joint swelling, pain, warm, stiff, worse AM, improve with activity, reduce range of movement, contractures.

sJIA, symmetrical, polyarticular, myalgia, abdominal pain, fever, rash.

pGALS screening.

Question 17

What investigations would you use for Group of chronic arthropaties in childhood?

Answer 17

FBC, markers of inflammation ESR CRP ferritin. RF, ANA, HLA subtype, slit lamp exam (anterior uveitis) XR, USS, MRI.

Question 18

What is the management of Juvenile idiopathic arthritis?

Answer 18

Holistic aproach: symptom tx (analgesia), steroids, DMARDS (MTX, entarcept anti TNFa)

Question 19

What are the complications and prognosis of someone with Juvenile idiopathic arthritis?

Answer 19

Anterior uveitis is asymptomatic, failure to screen this may lead to glaucoma, cataracts and blindness. THEREFORE DO SLIT LAMP EXAM!!!!

High proportion of children develop destructive bone disease. 30-40%, requiring early joint replacement.

Question 20

What is Legg-Calve-Perthes disease (Perthe disease)?

Answer 20

Idiopathic avascular necrosis of the capital femoral epiphysis of the femoral head.

Question 21

What is the aetiology of Perthe disease?

Answer 21

General: unknown, probably multifactoria. 25% bilateral (doe not occur at same time). May be due to altered growth pattern, trauma, and fibrinolysis defects like sickle cell crisis. Rapide epyphiseal growth and lack of supply keeping up.

Classification: Modified Elizabethtown – I sclerotic (withor without loss of height), II fragmentation (A early B late), III healing (A peripheral, B medial 1/3), IV healed.

Associated with sickle cell, premature, SES low, low BW, high parental age, passive smoking

Question 22

What is the epidemiology of Perthe Disease?

Answer 22

12/100k.

Question 23

What would you find in the history of Perthe Disease?

Answer 23

Limp: early sign, intermittent, abductor lurch, post exercise. Painles slimp.

Pain: classically painless, may have mild intermittent pain in anterior thigh or hip pain secondary to necrosis of affected bone, referred to medial aspect of ipsilateral knee or thigh.

Question 24

What would you find in the examination of Perthe disease?

Answer 24

Look: atrophy of the quad due to disuse. Leg length inequality, hip adduction flexion deformity, Trendelburg gait.

Feel: nil

Move: restricted ROM, mostly internal rotation and abduction . global rROM in late.

Roll test: supine position, roll foot on internal and external rotation. Guarding or spasm with internal rotation.

At risk femoral head signs: high age, high weight, loss of movement, adduction contracture, flexion with adduction

Question 25

What investigations would you do for Perthe Disease?

Answer 25

Bloods: FBC, CRP/ESR (septic arthritis), Hb electrophoresis (SCA)

Joint aspiration to exclude septic arthritis.

XR: AP and frog leg – Catterral at risk signs: gage sign, calcificaiton lateral to the epiphysis, sublaxation, epiphyseal angle, diffuse metaphyseal reaction.

Imaging: bone scan, arthrography, MRI.

Question 26

What is the management of Perthe Disease?

Answer 26

General: catterrall criteria and radiological grde, ET classification.

Containment theory: secure injured femoral head within socket and movement continued.

Conservative: only in healing stage >8yo.

Surgical: to achieve containment and salvage the joint, proximal femoral osteotomies, acetabular surgery, abduction osteotomies and chictomy.

Question 27

What are the complications and prognosis of Perthe Disease?

Answer 27

Permanent femoral head deformity, early OA.

Iowa long term follow up study: 40% had joint replacement, 10% disabling arthritis, 10% hip score<80%.