STEPTRACKERMUSCULOSKELETAL | PATHOLOGY + GENETICS + EMBRYOLOGY | HIGH-YIELD REVIEW

Skeletal Development Disorders

Inherited defects of cartilage, collagen and osteoclasts — and the growing-hip problems of childhood.

FOCUS ON
Achondroplasia: FGFR3 gain of function → short limbs, normal trunk and intelligence (endochondral only). Osteogenesis imperfecta: type I collagen → fractures, blue sclerae, hearing loss, dental defects — mimics abuse. Osteopetrosis: osteoclasts can't resorb → dense brittle bone, pancytopenia, nerve compression. Hip by age: DDH (newborn), Perthes (4–10), SCFE (obese teen).
DISORDER
MECHANISM · GENETICS
FEATURES
CLUE
Achondroplasia
most common skeletal dysplasia
FGFR3 gain of function → inhibits chondrocyte proliferation in growth plates; AD, mostly new mutations (older fathers)
Short proximal limbs, large head, frontal bossing, saddle nose, normal trunk; normal intelligence and lifespan
Spinal and foramen magnum stenosis
Thanatophoric dysplasia
Stronger FGFR3 activation
Severe micromelia, small thorax → lethal pulmonary hypoplasia
Most common lethal dysplasia
Osteogenesis imperfecta
COL1A1/COL1A2 → too little or abnormal type I collagen; mostly AD
Multiple fractures with minor trauma, blue sclerae, conductive hearing loss, opalescent teeth, ligament laxity, short stature
Type II lethal in utero · bisphosphonates
Osteopetrosis
Osteoclast failure (e.g., carbonic anhydrase II → can't acidify) → no resorption
Dense but brittle bones; marrow crowded → pancytopenia, extramedullary hematopoiesis; cranial nerve palsies (vision, hearing); "bone-in-bone"
CA II form: RTA · stem cell transplant (osteoclasts come from monocytes)
Cleidocranial dysplasia
RUNX2 (osteoblast transcription factor); AD
Absent/hypoplastic clavicles (shoulders touch), delayed fontanelle closure, extra teeth
Membranous bone defect
Fibrous dysplasia
Somatic GNAS activation → bone replaced by fibrous tissue and woven bone
Ribs, femur, skull; "ground glass" on X-ray; "Chinese letter" trabeculae; shepherd's crook deformity
Polyostotic + endocrine = McCune-Albright
Developmental dysplasia of the hip
Shallow acetabulum, lax capsule; female, breech, firstborn, oligohydramnios
Newborn: Ortolani (reduces) / Barlow (dislocates) clunk; asymmetric skin folds, leg-length difference
Ultrasound before 4–6 months · Pavlik harness
Legg-Calvé-Perthes disease
Idiopathic avascular necrosis of the femoral head
Boys 4–10: painless or mildly painful limp, ↓ abduction and internal rotation
Flattened, fragmented femoral head
Slipped capital femoral epiphysis
Shear through the weak growth plate; obesity, hypothyroidism, GH, adolescent growth spurt
Obese teen boy with hip or knee pain, limp, ↓ internal rotation; leg externally rotates on flexion
"Ice cream falling off the cone" · surgical pinning
Osgood-Schlatter disease
Traction apophysitis of the tibial tubercle (patellar tendon)
Active adolescents (jumping, running): anterior knee pain and tender bump
Self-limited

Mechanism — two ways to make bone

EndochondralCartilage model first
→
Growth plate chondrocytesFGFR3 brakes them
→
Long bones lengthenAchondroplasia defect
MembranousNo cartilage
→
Osteoblasts (RUNX2)
→
Skull, face, clavicleCleidocranial defect

In achondroplasia, membranous bone grows normally — the skull is large relative to the short limbs.

The limping child by age

AGE
LIKELY CAUSE
CLUE
Newborn
Developmental dysplasia
Ortolani/Barlow
1–4 years
Toddler fracture, septic arthritis
Fever, refuses to bear weight
3–8 years
Transient synovitis
After a viral illness, afebrile
4–10 years
Legg-Calvé-Perthes
Painless limp, boys
11–15 years
SCFE
Obese, knee pain
Adolescent athlete
Osgood-Schlatter
Tibial tubercle bump

How it's tested

COMMON CONFUSIONOsteogenesis imperfecta vs child abuse: both cause multiple fractures. OI adds blue sclerae, dental and hearing problems, and a family history.
THE TRAPOsteopetrosis bones look dense on X-ray but break easily — and the bone marrow failure (anemia, infections) is often what brings the child in.
YOUR APPROACHShort limbs vs fractures vs dense bone → gene (FGFR3, COL1, CA II, RUNX2) → bone formation type affected → associated findings.

If you see… think…

Short limbs, large head, normal trunk and intelligence → achondroplasia (FGFR3)
Child with many fractures, blue sclerae, hearing loss → osteogenesis imperfecta
Dense bones, pancytopenia, blindness, hepatosplenomegaly → osteopetrosis
Osteopetrosis with renal tubular acidosis → carbonic anhydrase II deficiency
Shoulders can be brought together in front of the chest → cleidocranial dysplasia
Ground-glass bone lesion + café-au-lait + precocious puberty → McCune-Albright
Breech-born girl with hip clunk → developmental dysplasia of the hip
7-year-old boy with painless limp, flattened femoral head → Legg-Calvé-Perthes
Obese 13-year-old with knee pain and limp → SCFE
Teen basketball player with painful tibial tubercle → Osgood-Schlatter