Achondroplasia

Achondroplasia is a congenital genetic disorder resulting in rhizomelic dwarfism and is the most common skeletal dysplasia. It has numerous distinctive radiographic features. 

Epidemiology

It occurs due to sporadic mutations in the majority of cases but can be inherited as an autosomal dominant condition. Homozygous achondroplasia is lethal. 

There is a prevalence of approximately 1 in 25,000-50,000 births with males affected more frequently than females ¹⁸.

Clinical presentation

Achondroplasia is the most common cause of short-limb dwarfism. Patients are of normal intelligence and motor function, presenting with delayed motor milestones. They may have specific neurologic deficits. Stenosis of the foramen magnum can, for example, present with difficulty swallowing or snoring.

Pathology

The disease results from a mutation in the fibroblast growth factor gene 3 (FGFR3) located on chromosome 4p16.3 which causes abnormal cartilage formation. These are cell surface receptors comprised of an extracellular domain with three immunoglobulin-like regions, a transmembrane domain and an intracellular tyrosine kinase ¹⁹. 

The mutation to the FGFR3 gene in achondroplasia is a gain of function mutation with constitutive activation of an inhibitory signal ^19,20. All bones that form by endochondral ossification are affected. Bones that form by membranous ossification are not affected, thus allowing the skull vault to develop normally.

Associations

• SADDAN syndrome: severe achondroplasia with developmental delay and acanthosis nigricans

Radiographic features

Almost all the bones of the skeleton are affected, and hence all parts of the body have bony changes with secondary soft tissue changes. Antenatally it is difficult to diagnose achondroplastic features until the 3^rd trimester ¹³.

Antenatal ultrasound 

Antenatally detectable sonographic features include:

• short femur length measurement: often well below the 5^th centile

  • the femur length (FL) to biparietal diameter (BPD) is taken as a useful measurement

• trident hand ¹¹: 2^nd, 3^rd, and 4^th fingers appear separated and similar in length

• separation of 1^st, 2^nd, 3^rd, and 4^th fingers

• protruding forehead: frontal bossing

• depressed nasal bridge

Plain radiograph / CT / MRI 

Features on radiographs, CT, and MRI are similar and discussed together here.

Cranial

• relatively large cranial vault with small skull base

• frontal bossing with the depressed nasal bridge (midfacial retrusion) ¹⁹

• narrowed foramen magnum

• cervico-medullary kink

• relative elevation of the brainstem resulting in a large suprasellar cistern and vertically-oriented straight sinus

• communicating hydrocephalus (due to venous obstruction at sigmoid sinus)

• large anterior fontanelle in infancy; may persist to 5 or 6 years of age ¹⁹

Also, see the achondroplastic base of skull abnormalities for further discussion.

Spinal 

• posterior vertebral scalloping

• progressive decrease in the interpedicular distance in the lumbar spine: decreased L5-S1 is pathognomonic

• gibbus: thoracolumbar kyphosis with bullet-shaped/hypoplastic vertebra (not to be confused with Hurler syndrome)

• short pedicle canal stenosis

• laminar thickening

• widening of intervertebral discs ⁸

• an increased angle between the sacrum and lumbar spine

Chest

• anterior flaring of the ribs 

• anteroposterior narrowing of the ribs

Pelvis and hips

• horizontal acetabular roof (decreased acetabular angle)

• small squared (tombstone or mickey mouse ear) iliac wings

• small trident acetabulum

• champagne glass type pelvic inlet

• short sacroiliac notches

Limbs

• metaphyseal flaring ⁸: can give a trumpet bone type appearance

• the femora and humeri are particularly shortened (rhizomelic shortening)

• long fibula: the fibular head is at the level of the tibial plateau

• bowing to mesial segment of legs ¹⁹

• the limbs may also appear thickened but are in fact normal in absolute terms; thickening is perceived due to reduced length

• trident hand

• chevron sign ^16,17

• the metacarpal and metatarsal bones, and in some cases the proximal phalanges, are short and of similar length

A useful mnemonic can be found here.

Treatment and prognosis

There is often a danger of cervical cord compression due to narrowing of the foramen magnum.

Treatment varies and is usually orthopedic, particularly to correct kyphoscolioses, as well as neurosurgical, to decompress the foramen magnum or shunt hydrocephalus ^6,7.

Overall prognosis is good, with near-normal life expectancy in heterozygous individuals. When homozygous, the condition is fatal due to respiratory failure ⁷.

History and etymology

Achondroplasia literally means "without cartilage formation", although the pathology is impaired endochondral ossification (see Pathology section above).

Differential diagnosis

The differential diagnosis is that of other less common skeletal dysplasias, including ⁶:

• achondrogenesis

• campomelic dysplasia

• thanatophoric dysplasia

• chondroectodermal dysplasia (Ellis-van Creveld syndrome)

See also

• causes of limb bowing: general differential for (lower) limb bowing 

• rhizomelic dwarfism: general differential for rhizomelic limb shortening

• achondroplasia (mnemonic)