Achondroplasia — Orthopaedic Issues

Achondroplasia is the most common form of short-limbed dwarfism and the most frequent skeletal dysplasia in clinical practice. It is caused by a gain-of-function mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, which inhibits endochondral ossification. Orthopaedic surgeons encounter achondroplasia patients throughout their career — from infancy through adulthood — and must be familiar with the diverse musculoskeletal complications that require management.

• Incidence: approximately 1 in 25,000 live births
• Genetics: autosomal dominant; FGFR3 mutation (Gly380Arg in 98% of cases) — gain-of-function mutation inhibits chondrocyte proliferation in growth plate; 80% of cases are de novo mutations (unaffected parents); 20% inherited from affected parent
• Homozygous achondroplasia: lethal in neonatal period due to respiratory compromise from extremely small chest
• Distinguishing features: rhizomelic shortening (proximal limb > distal), large head with frontal bossing, mid-face hypoplasia, trident hand configuration, lumbar hyperlordosis, genu varum
• Intelligence: normal — intellectual development unaffected in uncomplicated achondroplasia
• Vosoritide: recombinant C-type natriuretic peptide (CNP) analogue — FDA/EMA approved (2021) for increasing linear growth in children with achondroplasia; does not cure underlying mutation but significantly improves height velocity

• Endochondral ossification impaired — bones that grow by endochondral ossification (long bones, spine, base of skull) are shortened; intramembranous ossification (skull vault, clavicle) is normal — results in disproportionate macrocephaly
• Rhizomelia: proximal limbs (humerus, femur) more shortened than distal (radius/ulna, tibia/fibula); forearm typically held in flexion; elbow extension limited
• Foramen magnum stenosis: narrowing from abnormal skull base growth — compresses cervicomedullary junction; risk of sudden infant death and apnoea
• Spinal canal stenosis: interpedicular distance decreases caudally (opposite to normal); short, thick pedicles; reduced AP diameter of canal — lumbar stenosis is almost universal in adults
• Lumbar hyperlordosis and kyphosis: thoracolumbar kyphosis in infancy (common); usually resolves when walking begins; persistent kyphosis >30° requires management
• Genu varum: from tibial and fibular growth disparity and ligamentous laxity — affects most patients to variable degree

• Most critical issue in infancy — foramen magnum stenosis can cause sudden death, central apnoea, hypotonia, and cervicomedullary compression; all achondroplasia infants require surveillance
• Symptoms: hypotonia, apnoea (central or obstructive), feeding difficulties, excessive sweating, clonus, hyperreflexia, developmental delay
• Investigations: MRI craniocervical junction; polysomnography (sleep study) to detect central apnoea; neurophysiology (SSEP/BAER) for cord function
• Indications for foramen magnum decompression: symptomatic cord or brainstem compression, central apnoea on polysomnography, abnormal neurophysiology, progressive neurological signs
• Surgical decompression: posterior craniocervical decompression (suboccipital craniectomy + C1 laminectomy) — excellent results when performed timely; significant improvement in neurological function
• American Academy of Pediatrics (AAP) guidelines: all achondroplasia infants should have MRI craniocervical junction and polysomnography in first year of life; regular neurodevelopmental surveillance

Symptomatic lumbar spinal stenosis affects the majority of adults with achondroplasia and is the most common cause of significant disability and reduced quality of life in this population.

• Symptoms: neurogenic claudication (leg pain, weakness, or numbness with walking that relieves with sitting/flexion); lumbar radiculopathy; bowel and bladder dysfunction in severe cases
• Neurogenic claudication in achondroplasia: typically presents in 3rd–4th decade; patient history of needing to sit down or lean forward while walking (flexion relieves stenosis)
• Imaging: MRI lumbar spine — shows multilevel stenosis, short pedicles, disc bulge, ligamentum flavum hypertrophy; multiple levels typically involved
• Surgical management: multilevel laminectomy with or without fusion; decompression alone may suffice; fusion added for instability or significant deformity; results generally good for neurogenic claudication
• Thoracolumbar kyphosis: if significant (>30°), anterior column collapse risk; posterior instrumented fusion may be required
• Avoid single-level decompression if multiple levels involved — inadequate decompression leads to persistent symptoms and early reoperation

• Genu varum is nearly universal; arises from asymmetric growth of tibia and fibula (fibula relatively overgrows) and from ligamentous laxity at the knee
• Most children with achondroplasia have physiological genu varum that is functional; surgical intervention reserved for symptomatic cases with progressive deformity, thrust, or medial compartment loading
• Indications for correction: varus >15°, progressive lateral thrust, knee pain, functional impairment
• Hemiepiphysiodesis (guided growth): tension band plate (8-plate or staple) on medial proximal tibia — corrects varus progressively during remaining growth; minimally invasive; reversible
• Tibial osteotomy: for skeletally mature patients or severe deformity — opening or closing wedge; can be combined with Ilizarov lengthening
• Fibular head: prominent fibular head from relative overgrowth — rarely causes problems; proximal fibular epiphysiodesis or fibular shortening if causing functional impairment

Limb lengthening in achondroplasia is one of the most controversial topics in paediatric orthopaedics, involving complex ethical, functional, and psychosocial considerations.

• Potential gain: 30–40 cm of total height gain possible with combined humeral, femoral, and tibial lengthening performed over multiple surgical stages
• Typical approach: bilateral tibial lengthening first (most functional gain), then femoral, then humeral; each staged over 12–18 months
• Intramedullary lengthening nails (PRECICE, STRYDE): now preferred over external fixators — reduce pin-site infection, joint stiffness, psychological burden; lengthening achieved magnetically through skin with external remote controller
• Complications: joint contracture (knee most common), nerve palsy (peroneal with tibial lengthening), pin-site infection (external fixator), fracture through regenerate bone, premature consolidation, delayed consolidation
• Ethical considerations: decision should involve the patient (when old enough), family, psychologist, and multidisciplinary team; Little People organisations recommend against cosmetic lengthening; many achondroplasia adults live full functional lives without lengthening
• Vosoritide therapy: may reduce the magnitude of lengthening required if started in childhood — ongoing clinical trial data awaited

• Difficult airway: macrocephaly, mid-face hypoplasia, limited neck extension, and potential foramen magnum stenosis — anticipate and prepare for difficult intubation in all achondroplasia patients
• Atlantoaxial instability: assess with flexion-extension MRI before elective surgery — avoid extreme neck positions during positioning and intubation
• Regional anaesthesia challenges: short pedicles and narrow epidural/intrathecal spaces; unpredictable spread of spinal anaesthesia — use reduced doses; have experienced anaesthetist
• Obstructive sleep apnoea: extremely common — assess with sleep study preoperatively; postoperative monitoring for apnoea
• Positioning: standard tables may not accommodate body proportions — padding and positioning aids required

• Multidisciplinary care is mandatory: orthopaedics, neurosurgery (foramen magnum, spinal stenosis), neurology, respiratory medicine (sleep apnoea, central apnoea), genetics, psychology, and allied health — no single specialty can manage achondroplasia alone
• Sudden infant death risk: highest in first year — cervicomedullary compression from foramen magnum stenosis is the leading preventable cause of death in achondroplasia; early MRI and sleep study are life-saving interventions
• Vosoritide (BMN111): daily subcutaneous injection; approved by FDA (2021) and EMA (2021); increases height velocity by approximately 1.6 cm/year above untreated controls; long-term skeletal and functional outcome data still accruing; does not address spinal stenosis or foramen magnum narrowing
• Spinal decompression extent: multilevel laminectomy must be sufficient — partial decompression is a common cause of failure; include all stenotic levels on MRI; augment with posterolateral fusion if instability risk (spondylolisthesis, significant kyphosis, young patient)
• Pregnancy in achondroplasia: normal conception; if both parents have achondroplasia — 25% risk homozygous (lethal), 50% heterozygous (affected), 25% unaffected; caesarean section mandatory due to small pelvis; neuraxial anaesthesia challenging

• FGFR3 gain-of-function mutation (Gly380Arg); autosomal dominant; 80% de novo mutations
• Rhizomelic shortening — proximal limbs more affected than distal; normal intramembranous ossification
• Foramen magnum stenosis: most critical infant complication; can cause sudden death; MRI + polysomnography in all achondroplasia infants in first year
• Lumbar spinal stenosis: almost universal in adults; neurogenic claudication; multilevel laminectomy required
• Interpedicular distance decreases caudally in achondroplasia — opposite to normal; explains why multilevel lumbar stenosis is so severe
• Genu varum: hemiepiphysiodesis (guided growth) for skeletally immature; tibial osteotomy at maturity
• Limb lengthening: PRECICE intramedullary nail preferred; 30–40 cm total gain possible in staged procedures
• Vosoritide: CNP analogue; FDA/EMA approved 2021; improves height velocity; does not cure
• Difficult airway in ALL achondroplasia patients — prepare and communicate to anaesthetic team preoperatively
• Homozygous achondroplasia: lethal; from two affected parents — 25% risk per pregnancy