����Vlog

Achondroplasia has autosomal dominant inheritance. About 75-80% of people with achondroplasia are the first in their family, due to a new mutation.^2,3��

Achondroplasia is caused by a mutation (gene change) in the fibroblast growth factor receptor-3 (FGFR3) gene.^1,2�� Almost everyone with achondroplasia has a change in the same spot in the FGFR3 gene. Specifically, mutations that change the amino acid glycine to arginine at position 380 (G380R) of the FGFR-3 protein account for more than 97% of all reported cases of achondroplasia.

Typically, the FGFR-3 protein functions in a signaling pathway to slow linear growth in the growth plates of the long bones. The gene change that causes achondroplasia turns on the pathway more than it should, so bones grow slower and end up shorter than they typically would. This type of change associated with an increased ability is called a "gain-of-function" mutation.¹

Achondroplasia causes disproportionate short stature. Specifically, the limbs (arms and legs) are small when compared to the trunk. Within the arms and legs, the upper segment is shorter, which is called rhizomelia. The average adult height is 52" in men and 49" in women with achondroplasia. Individuals with achondroplasia have average intelligence and can lead very rich and productive lives.

Face and Skull

• The head circumference may be larger than typical.
• The forehead tends to be prominent. The medical term for this is frontal bossing.
• The nasal bridge tends to be depressed.
• The mid-face is underdeveloped, which is called midface hypoplasia or midface retrusion.
• The foramen magnum, which is the opening in the skull base through which the spinal cord passes, is smaller than typical.

Trunk, Chest and Spine

• Thoraco-lumbar kyphosis (TLK) is a pooching out in the lower back. Almost all infants with achondroplasia have this, and it is a typical finding. TLK is thought to be caused by the larger head size and low muscle tone in children who are not yet walking. It improves without treatment in 90% of children with achondroplasia after they get good trunk control and begin to walk.
• After a child is a good walker, individuals with achondroplasia develop exaggerated lumbar lordosis, also called sway back.
• The spinal canal is smaller than typical in achondroplasia.

Arms and Legs

• Loose joints are typical.
• Even though most joints are loose, typically the elbows cannot be fully extended due to a bony difference. This rarely causes symptoms or loss of function.
• In infancy and early childhood there is extra space between the third and fourth fingers. This is sometimes called a trident hand, and usually is not as obvious in later childhood.
• The fingers are short and broad.

X-Ray Characteristics

• Long bones are relatively wide and shorter than typical.
• In infancy, the top of the femurs have distinctive shapes
• Fibulas tend to be longer than tibias in the lower leg.
• Spacing between vertebral pedicles decreases rather than increases in the lumbar spine as you move from head to pelvis.
• The pelvis is short and broad with wide, nonflaring iliac wings.

For parents of typical stature, achondroplasia is sometimes suspected when short limbs and a larger head size are noted on a prenatal ultrasound in the third trimester. The diagnosis can be confirmed by genetic testing by amniocentesis before birth, or by genetic testing or X-rays after birth.

For those with a family history of achondroplasia, chorionic villus sampling (CVS) is another option that can be performed earlier in the pregnancy to look for the genetic change associated with achondroplasia. It is also possible to do genetic testing before pregnancy, as part of in vitro fertilization (IVF).

Most babies with achondroplasia have average lengths and weights at birth. As many as 15% of children with achondroplasia are not recognized at birth.¹

In the newborn, infant, older child or adult, the diagnosis of achondroplasia can be based on physical and radiologic (X-ray) examinations. Testing of the FGFR3 gene can also be done for confirmation.

Foramen Magnum Stenosis

Essentially all children with achondroplasia have a smaller than typical foramen magnum. The foramen magnum is the opening through which the spinal cord leaves the head to travel down the spinal column.

For most children this does not cause a problem. However, there are approximately 15-20% of children with achondroplasia for whom this opening is too small for the spinal cord, leading to spinal cord compression.⁵ When the spinal cord is squeezed, it can lead to a difference in the neurologic exam, weakness, slower than expected gross motor skills, and/or central sleep apnea. This requires surgical correction by a neurosurgeon because it can cause complications, and even be life-threatening in rare instances. This is typically a problem of infancy, and not of older children/adults.

Hydrocephalus

A larger head size is common in achondroplasia, but it is not a problem unless there is also increased pressure from fluid in the skull. One clue to this is that increased pressure leads to the head size growing faster than expected. Head circumference growth charts for achondroplasia are available. If a jump in head growth is noticed, or the soft spot (fontanelle) feels harder than typical, a referral to a neurosurgeon would be recommended for further evaluation. This can be treated by a ventriculoperitoneal shunt (a tube that drains excess fluid from the brain into the abdominal cavity). This is typically a problem of infancy, and not of older children/adults.⁶

Sleep Apneas or Sleep-Disordered Breathing

Sleep disordered breathing (apnea) is common in achondroplasia. In a large cohort, as many as 38% of children with achondroplasia had severe apnea.⁷ There are two types of apnea, and they will be discussed separately.

• Obstructive apnea — results from the blockage of airflow into and out of the lungs with appropriate respiratory drive. This is the most common type of apnea in achondroplasia because of the midface retrusion and hypotonia of the pharyngeal muscles, and the fact that they have a "smaller pipe" for the air to travel through. This can lead to chronic snoring and disturbed sleep with extended pauses in breathing. Symptoms of obstructive apnea can include tiredness, irritability, and daytime sleepiness. Treatment for obstructive apnea can include weight reduction, adenoidectomy/tonsillectomy, continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) at night by nasal mask to keep the airways open.
• Central apnea — happens when there is a failure of the respiratory centers in the brain to control the process of breathing during sleep. In the brainstem, the respiratory centers are near the foramen magnum. So, if the foramen magnum is too small and is compressing the spinal cord, central apnea can result.

Genu Varum (Bowlegs)

Genu Varum (bowlegs) is much more common than genu valgus (knock knees) in achondroplasia.^3,6 Both require follow-up as a child grows because the bowing can worsen. Bowlegs can result in symptoms around the knee such as pain that limits walking and instability. Components of genu varum involve inward bowing both above (femur) and below (tibia) the knee, as well as above the ankle (tibia). While some speculate that overgrowth of the fibula can result in bowing, the relationship is not clear. There is often associated internal tibial torsion with genu varum, result in in-toeing of the feet.

While it is possible to treat bowing by cutting the bones (osteotomies) and straightening the legs, there are good recent results with gradual correction. Prior to skeletal maturity, temporary fixation of one side of the growth plate allows angular correction of bowing. This can be achieved using a small plate or screw, which are removed when the correction is complete. Bracing is not effective for treatment, as it is not possible to exert consistent correction on the knees that impacts growth.

Symptomatic knee arthritis is not a frequent problem in adults with achondroplasia and this can be a reassuring fact for parents. Current recommendations are to undergo surgery only in the presence of bothersome symptoms (pain or instability), or if there is severe, progressive deformity.

Spinal Stenosis

Spinal stenosis in the lumbar spine is relatively common in adults with achondroplasia, though it can occur at any age.^3,6 The spinal canal is narrow, but the spinal cord is a typical size, so there is less room for the spinal cord in the spine of someone with achondroplasia. In some people, this narrowing of the spinal canal results in compression of the nerves. Symptoms include activity-related leg pain that is relieved by squatting down, tingling, feeling of pins and needles, or numbness in the feet, (paresthesias), weakness of the legs, or rarely, disturbances in control of bladder or bowel function (incontinence). X-rays, CT and MRI scans of the lower spine, can be used to diagnose and manage the issue. We believe that obesity greatly increases the risk of this problem developing.

Fixed Thoracolumbar Kyphosis (Fixed TLK)

As mentioned above, infants with achondroplasia typically have a thoraco-lumbar kyphosis (TLK).^3,6 In most cases, as the child begins to walk, the TLK will spontaneously resolve without treatment. In some children however, the TLK will become fixed or permanent. Prolonged unsupported sitting likely contributes to fixed kyphosis. Typically, when a child is laid on their belly, the thoraco-lumbar region will flatten, indicating that the TLK is flexible. When the kyphosis is not flexible, there is increased concern that it will require treatment. Bracing has mixed evidence in treating this problem and, if severe enough, surgery may be required to straighten the spine and take tension off of the spinal cord and nerves.

Obesity

Obesity is a common problem in children and adults of all statures, but especially with skeletal dysplasias like achondroplasia.^3,6 ��A weight-for-height chart is available specifically for individuals with achondroplasia and is a useful guide for weight management. Attention to weight issues in childhood (after 2 years of age) is important, as we believe that obesity will significantly increase the risk for spinal problems in adults with achondroplasia. Equally important to dietary management is attention to physical activities and appropriate exercise.

Speech and Hearing

The midface retrusion in achondroplasia can potentially lead to problems in the ear, nose, and throat area.^3,6

The eustachian tube is the connection between the middle ear and the upper throat. In achondroplasia, the anatomy of this tube is different, and fluid cannot drain as well from the middle ear. Over the long term, this can lead to conductive hearing loss. Hearing should be assessed frequently. Ear infections are easily treated, and the use of middle ear tubes is common.

The midface hypoplasia can also lead to dental crowding and the need for palate expanders and orthodontics.

Pregnancy

Females with achondroplasia typically require a Cesarean section for delivery due to the reduced size and shape of the pelvis.

Children with achondroplasia will develop head control, sitting, crawling, and walking at older ages than their peers, which is to be expected. Given the differences in body proportions, it is inappropriate to use the developmental charts of a typical child to assess a child with achondroplasia. There are specialized developmental charts for children with achondroplasia, and it is critical that these be used.⁶

We believe physical therapy should be reserved for individuals with true gross motor delays based on expectations for a child with achondroplasia, after common causes have been ruled out. If a child has gross motor delays in infancy, we recommend first evaluating for critical foramen magnum stenosis, so that the problem can be treated instead of the symptoms. Exercises/positioning designed for a typical child to catch up to a typical timeline can increase the risk for cord compression related to foramen magnum stenosis, and/or increased the likelihood of a fixed TLK.

Extreme care should be taken in the position and handling of infants to minimize sudden abrupt head and neck motion due to the smaller foramen magnum. When children get older, activities should be avoided that put them at risk for neck injuries, such as contact sports, high diving, gymnastics, tumbling, and trampolines.

Diminishing motor milestones, decreased endurance, apnea, or any neurological symptoms should be evaluated by an experienced medical provider.

To avoid a fixed TLK, proper back support should be provided for every child in infancy, including reclined seating and no “hammock-style” backs, until the child has the strength to sit on their own. Also recommend avoiding soft-backed swings, umbrella strollers, and jumpers. Backpack carriers and front sling/carriers should not be used until the child gains complete and total head and trunk control.

Properly installed rear-facing car seats with neck support when traveling in a car are important safety measures. The car seat should remain rearward facing until the child is at least 20 pounds or the weight requirement of your state, whichever is higher.

Head size should be monitored carefully at least every three to six months in the first few years of life. We believe that the parents should become comfortable with feeling the anterior fontanelle or soft spot located on top of the infant’s skull about once a week. The fontanelle should be soft and flat. If the fontanelle becomes hard (like a tabletop) or bulging when the child is healthy and at rest, then this should be brought to immediate medical attention as it could be a sign of increased pressure on the brain in infancy.

Speech delay may indicate underlying conductive hearing loss, so hearing should be assessed in addition to seeking speech therapy. Ears should also be assessed after each ear infection to make sure fluid has drained.

Sleep disturbance such as chronic snoring and/or long witnessed pauses may indicate obstructive sleep apnea or central sleep apnea from cord compression and should be brought to an experienced medical provider’s attention. There is a risk for obstructive sleep apnea both as a child and as an adult.

Overall, we also recommend you talk about achondroplasia — both with your child and others — as a difference rather than a problem. Your attitude can help your child develop good self-esteem. Treat the child according to age and not size and encourage others to do the same. Also, find ways to adapt. For example, get a light switch extender and a stepstool so your child can turn the lights on and off and get to the sink independently to wash their hands. Encourage your child’s school to make modifications/accommodations for your child to maximize their independence in an age-appropriate way. Get involved with groups like the . Getting to know other people with achondroplasia and other forms of dwarfism can help your child feel connected.

1. Hoover-Fong JE, Alade AY, Hashmi SS, Hecht JT, Legare JM, Little ME, Liu C, McGready J, Modaff P, Pauli RM, Rodriguez-Buritica DF, Schulze KJ, Serna ME, Smid CJ, Bober MB. Achondroplasia Natural History Study (CLARITY): a multicenter retrospective cohort study of achondroplasia in the United States. Genet Med. 2021 Aug;23(8):1498-1505.
2. Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, Kaitila I, Loughlin J, Munnich A, Sykes B, Bonaventure J, Francomano CA. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998 Sep;63(3):711-6.
3. Hoover-Fong J, Scott CI, Jones MC; COMMITTEE ON GENETICS. Health Supervision for People With Achondroplasia. Pediatrics. 2020 Jun;145(6):e20201010. doi: 10.1542/peds.2020-1010. PMID: 32457214.
4. Spranger JW, Brill, PW, Hall C, Nishimura G, Superti-Furga, A, Unger, S. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2018.
5. Legare JM, Liu C, Pauli RM, Alade AY, Hashmi SS, Campbell JW, Smid CJ, Modaff P, Little ME, Rodriguez-Buritica DF, Serna ME, Hecht JT, Hoover-Fong JE, Bober MB. Achondroplasia Natural History Study (CLARITY): 60-year experience in cervicomedullary decompression in achondroplasia from four skeletal dysplasia centers. J Neurosurg Pediatr. 2021 Jun 4:1-7.
6. Hunter AG, Bankier A, Rogers JG, Sillence D, Scott CI Jr. Medical complications of achondroplasia: a multicentre patient review. J Med Genet. 1998 Sep;35(9):705-12.
7. Mogayzel PJ Jr, Carroll JL, Loughlin GM, Hurko O, Francomano CA, Marcus CL. Sleep-disordered breathing in children with achondroplasia. J Pediatr. 1998 Apr;132(4):667-71.