summary Achondroplasia is a common congenital skeletal dysplasia caused by a sporadic or autosomal dominant gain-of-function mutation in FGFR3 gene. Patients present with rhizomelic dwarfism, lumbar and foramen magnum stenosis, frontal bossing, and normal intelligence. Diagnosis is usually made based on typical clinical and radiographic features on skeletal survey. Treatment involves observation and physical therapy for majority of anomalies. Surgery is indicated in patients with foramen magnum stenosis with sleep apnea or cord compression and progressive spinal stenosis that fails nonoperative treatment Epidemiology Incidence incidence most common skeletal dysplasia 80-90% of cases of dwarfism prevalence 1 in 15,000-30,000 Demographics no gender predominance most diagnosed in early infancy and in utero Risk factors advanced paternal age >50 years of age is 1 in 1,875 >35 years of age still increased risk Etiology Pathophysiology receptors FGFR3 login to view 12 more bullets signaling pathways four main pathways activated by FGFR3 login to view 6 more bullets modulators C-type natriuretic peptide (CNP) binds to natriuretic peptide receptor B (NPR-B) login to view 3 more bullets Genetics inheritance pattern sporadic mutation 80% login to view 1 more bullet autosomal dominant (AD) 20% 100% penetrance mutation chromosome 4P point mutation FGFR3 (Gly1138 to Arg substitution) login to view 4 more bullets Associated conditions medical conditions short stature login to view 3 more bullets obesity hearing loss tonsillar hypertrophy frequent otitis media spinal manifestations thoracolumbar kyphosis login to view 3 more bullets foramen magnum stenosis (FMS) login to view 2 more bullets lumbar stenosis login to view 7 more bullets lumbar hyperlordosis login to view 3 more bullets Presentation Symptoms general normal intelligence short stature delayed motor milestones hearing impairment recurrent ear infections weight gain symptoms of foramen magnum stenosis excessive snoring or apnea difficulty swallowing login to view 1 more bullet weakness symptoms of spinal stenosis pseudoclaudication and standing discomfort numbness and paresthesias weakness Physical exam rhizomelic dwarfism proximal portion of limb is shorter than distal (ie humerus shorter than forearm) normal trunk adult height ~ 50 inches facial features macrocephaly frontal bossing (broad forehead) midface hypoplasia chest anterior flarring of ribs AP narrowing of ribs small thoracic cage extremities brachydactyly (short digits) trident hands (fingers same length with divergent ring and middle fingers) limited elbow extension radial head subluxation posterior bowing of humerus hypermobile hips and knees genu varum muscular hypotonia spine thoracolumbar kyphosis lumbar hyperlordosis foramen magnum stenosis login to view 3 more bullets Imaging Radiographs recommended views skeletal survey AP pelvis and femur login to view 1 more bullet findings thoracolumbar spine login to view 5 more bullets pelvis and extremities login to view 6 more bullets MRI indications evaluate spinal stenosis assess foramen magnum stenosis findings narrowing of foramen with obliteration of posterior subarachnoid space posterior "nicking" or "waisting" of cord cord signal changes on T2 syrinx DIAGNOSIS Prenatal diagnosis ultrasound incidentally found during 2nd or 3rd trimester ultrasound login to view 2 more bullets cell-free fetal DNA noninvasive prenatal testing with high sensitivity/specificity Skeletal survey confirms diagnosis along with typical clinical features in most cases Molecular genetic testing of FGFR3 mutation indication atypical presentation login to view 1 more bullet differentiate from similar disorders Sleep studies indication evaluate for apnea in all infants DIFFERENTIAL DIAGNOSIS Hypochondroplasia rhizomelic dwarfism with similar presentation defining features milder shortness (taller) and bodily disproportions seizures and cognitive abnormalities more common with hypochondroplasia issues related to craniocervical junction less common different mutation of FGFR3 gene (Asn540 to Lys substitution) Thanatophoric dysplasia rhizomelic dwarfism defining features typically lethal in perinatal period login to view 1 more bullet different mutation of FGFR3 gene (Lys650 to Glu substitution) Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN syndrome) rhizomelic dwarfism defining features more severe global developmental delays seizures more common acanthosis nigricans - progressive skin disorder with thick, dark, velvety skin different mutation of FGFR3 gene (Lys650 to Met substitution) Pseudoachondroplasia spondyloepiphyseal dysplasia with few similarities except for rhizomelic dwarfism defining features no craniofacial features generally normal at birth and diagnosed at 2-3 years of age with a significant drop in growth early, severe dysplasia of hips lack of spinal stenosis cervical instability due to odontoid hypoplasia COMP gene mutation Treatment - Spine Conditions Foramen magnum stenosis nonoperative observation login to view 6 more bullets operative surgical decompression of foramen magnum login to view 10 more bullets Thoracolumbar kyphosis nonoperative observation login to view 16 more bullets bracing login to view 13 more bullets operative posterior fusion with instrumentation +/- anterior decompression login to view 8 more bullets Lumbar stenosis nonoperative weight loss, physical therapy, corticosteroid injections login to view 2 more bullets operative multilevel laminectomy and fusion login to view 18 more bullets Lumbar hyperlordosis nonoperative observation login to view 1 more bullet physical therapy login to view 2 more bullets Spine-related complications recurrent foramen magnum stenosis cerebral spinal fluid leaks malpositioned screw abnormal pedicle morphology neurologic complication overcorrection malpositioned screw use of wiring or laminar hooks post-laminectomy kyphosis very common following decompression for spinal stenosis add instrumentation Treatment - Extremity Conditions Genu varum nonoperative indication login to view 1 more bullet technique login to view 2 more bullets outcomes login to view 1 more bullet operative tibial +/- femur osteotomies login to view 11 more bullets Short stature nonoperative growth hormone therapy login to view 6 more bullets vosoritide login to view 9 more bullets operative lower limb lengthening login to view 12 more bullets upper extremity lengthening login to view 15 more bullets Complications Medical hydrocephalus treatment login to view 1 more bullet otolaryngeal problems incidence login to view 2 more bullets treatment login to view 1 more bullet apnea risk factors login to view 2 more bullets sudden infant death syndrome (SIDS) incidence login to view 1 more bullet risk factors login to view 1 more bullet PROGNOSIS Life expectancy 61 years of age 10 years less than general population highest mortality rates are <4 years of age risk of sudden unexpected death in infancy rates have decreased over time login to view 1 more bullet Quality of life lower quality-of-life across four subdomains health and functioning login to view 2 more bullets social and economic login to view 2 more bullets psychological spiritual family login to view 1 more bullet