Hypochondroplasia
Hypochondroplasia is a genetic condition that affects how bones grow, leading to short stature and shortened limbs. While it shares similarities with achondroplasia, its features are often milder and may not be noticed until early childhood.
Table of contents
- What is Hypochondroplasia?
- Signs and Physical Characteristics
- What Causes Hypochondroplasia?
- How is Hypochondroplasia Diagnosed?
- Medical Problems That Can Happen
- Treatment and Management
- How Hypochondroplasia is Inherited
- Living with Hypochondroplasia
What is Hypochondroplasia?
Hypochondroplasia is a skeletal dysplasia, which means it is a condition that affects how cartilage and bone grow[1]. Cartilage is the soft connective tissue between bones that normally turns into bone as a child grows[9]. In hypochondroplasia, this process happens more slowly than usual, especially in the long bones of the arms and legs[1].
This condition causes disproportionate short stature, meaning that while the person is shorter than average, their arms and legs are particularly short compared to the length of their body or trunk[5]. The features of hypochondroplasia are similar to those seen in achondroplasia, but they tend to be milder[8].
Hypochondroplasia is rare. Studies suggest it occurs in approximately 1 in 15,000 to 40,000 births[7][9]. The condition affects males and females equally[7]. Because the features can be mild, many people with hypochondroplasia are not aware they have the condition, which means the true number of cases may be higher[7].
Signs and Physical Characteristics
People with hypochondroplasia have short stature, meaning their height is less than other people of the same age[1]. The average adult height for someone with hypochondroplasia ranges from 138 centimeters to 165 centimeters (about 4 feet 6 inches to 5 feet 5 inches) for males, and from 128 centimeters to 151 centimeters (about 4 feet 2 inches to 4 feet 11 inches) for females[5][7].
Physical characteristics that may be present include[1][9]:
- A larger head (relative macrocephaly)
- A stocky build
- Arms and legs that are short compared with the body
- Short fingers
- Broad, short hands and feet
- Bow legs (knees curve outward)
- Curved spine, especially an inward curve at the lower back (lordosis)
- Limited ability to fully straighten the elbows
- Mild joint looseness in other joints
Growth tends to slow down during toddlerhood to early school-age years[9]. Children usually present as toddlers or at early school age with decreased growth that leads to short stature and limb disproportion[8]. The physical features become more noticeable over time[8].
Not every person with hypochondroplasia has all these characteristics. There is considerable variation from person to person[1]. Sometimes the growth differences are so small that hypochondroplasia is not diagnosed until later in life[1].
What Causes Hypochondroplasia?
Hypochondroplasia is caused by a change (mutation) in a gene called FGFR3, which stands for fibroblast growth factor receptor 3[1][9]. About 70 percent of people with hypochondroplasia have a change in this gene[5][7].
The FGFR3 gene makes a protein that plays an important role in how bones grow. Its normal job is to slow down growth in the growth plates of long bones[5]. When there is a mutation in this gene, the protein becomes overactive, which means it slows down bone growth more than it should[2][9]. This causes bones to grow slower and end up shorter than they typically would[1].
In the remaining 30 percent of people with hypochondroplasia, no change is found in the FGFR3 gene even though they have the signs and symptoms of the condition[7]. This does not necessarily mean they do not have hypochondroplasia. The gene change might not be found by current technology, or they may have a change in a different gene that has not yet been identified[1][7].
How is Hypochondroplasia Diagnosed?
Diagnosing hypochondroplasia can be challenging because the features may be mild, especially in young children[7]. Doctors might diagnose hypochondroplasia before birth through prenatal ultrasound, genetic testing through amniocentesis, or chorionic villus sampling[1][5]. However, hypochondroplasia is not typically detected by ultrasound during pregnancy[5].
Most of the time, doctors diagnose the condition at birth or early in childhood[1]. When a child is shorter than other children the same age or has short arms and legs, doctors perform an examination and tests to find the cause[1]. The diagnosis is usually made by identifying the physical features known to appear in hypochondroplasia along with findings from X-rays[7].
X-rays may show specific bone changes including[8]:
- Shortening of long bones with mild widening at the ends
- Narrowing of spaces between parts of the spine bones
- Short, broad upper leg bone where it meets the hip
- Squared, shortened hip bones
Genetic testing can confirm the diagnosis if a change in the FGFR3 gene is found[5][7]. However, the absence of a gene change does not rule out hypochondroplasia[7].
Without a definitive genetic diagnosis, individuals may be classified as having idiopathic short stature, which is a term used when no medical cause of short stature can be identified[2]. This uncertainty can affect the timeliness and quality of care[2].
Medical Problems That Can Happen
Most children with hypochondroplasia do not have every medical problem listed here, and there is a lot of variation from person to person[1]. The majority of individuals with hypochondroplasia do not have significant medical complications related to their condition[5].
Medical problems that can occur include[1][8][9]:
- Sleep apnea (difficulty breathing during sleep)
- Obesity
- Seizures, particularly temporal lobe epilepsy
- Learning disabilities
- Mild to moderate intellectual disability (though this is uncommon and most people have average intelligence)
- In young children: narrowing of the opening at the bottom of the skull (foramen magnum stenosis)
- In adults: narrowing of the lower spinal canal (lumbar spinal stenosis)
- Joint pain, especially after exercise or physical activity
- Recurrent ear infections
Medical complications that are common in achondroplasia, such as foramen magnum stenosis, spinal stenosis, leg bowing, and obstructive apnea, occur less frequently in hypochondroplasia[8]. However, intellectual disability and epilepsy may be more common in hypochondroplasia than in achondroplasia[5][8].
People who have hypochondroplasia should get regular medical checkups[1]. This helps doctors find and treat any medical problems right away[1].
Treatment and Management
There is no cure for hypochondroplasia, but doctors and scientists are working on medicines that can help[1]. Treatment focuses on managing related problems as they arise.
Children growing up with hypochondroplasia can live long, productive lives[1]. Management is best provided by a team of specialists including experts in genetics, bone health (orthopedics), the nervous system (neurology and neurosurgery), ear, nose and throat problems, as well as physical, occupational, and speech therapies[5].
Common management approaches include[5][7][8]:
- Surgery to correct bowing of the legs if it causes symptoms
- Treatment for spinal problems by orthopedists and neurosurgeons
- Physiotherapy for joint pain
- Standard treatment for seizures if they occur
- Developmental and educational support as needed
- Assessment for learning disabilities and special education if appropriate
Human growth hormone therapy has been given to some children with hypochondroplasia, but it has not been shown to significantly increase final adult height[7].
A medication called vosoritide has shown promising results in research studies. This drug was previously approved for treating children with achondroplasia and is now being studied for hypochondroplasia[10][12]. Children with hypochondroplasia who received vosoritide treatment for one year showed a significant increase in growth rates[12]. However, as of now, there are no approved medications specifically for treating short stature in children with hypochondroplasia[12].
Adaptations or accommodations in the home, school, workplace, vehicles, and other places may be necessary because of short stature and limited reach[5].
How Hypochondroplasia is Inherited
Hypochondroplasia is inherited in an autosomal dominant pattern[5][7]. This means that inheriting one changed FGFR3 gene is enough for a person to be affected and show signs of hypochondroplasia[5].
A child can inherit hypochondroplasia if either parent has it[1]. For a couple in which one parent has hypochondroplasia, there is a 50 percent chance with each pregnancy of having a child with the condition[5][7].
However, most children born with hypochondroplasia have a new gene change that happened before birth, and neither parent has the condition[1][5]. The gene change seems to occur frequently as a new event, called a spontaneous or de novo mutation[7]. For an average-sized couple who have had one child with hypochondroplasia due to a new mutation, the chance of having another child with hypochondroplasia is very low[5].
Families where hypochondroplasia has been diagnosed should seek genetic counseling[7]. A genetic counselor can help families understand how hypochondroplasia can run in families and what the risks are for future pregnancies[1].
Prenatal diagnosis is available for couples in which one or both parents have hypochondroplasia through chorionic villus sampling or amniocentesis, but only if a mutation in the FGFR3 gene has been identified[5][7]. If the mutation has not been identified, ultrasound scanning is the only method of prenatal testing[7].
Living with Hypochondroplasia
Individuals with hypochondroplasia have average intelligence and can lead very rich and productive lives[18]. People with hypochondroplasia can lead productive and independent lives[22].
Support is available for children with hypochondroplasia and their families from various organizations[7]. Connecting families with local resources and support is important[8].
Families face various challenges, including how society treats their child. Some families have dealt with unkind comments from other children and adults[16]. Even within the dwarfism community, children with hypochondroplasia may feel they are in an “in between” space because their features are often less pronounced than in other conditions[16].
Research has shown that children with hypochondroplasia have lower quality of life scores as reported by parents[17]. Understanding quality of life helps doctors provide better care and support[17].
As children grow, they may have more questions about their condition[16]. Helping others become aware of hypochondroplasia and the importance of treating people with respect regardless of how they look is an important part of advocacy[16].
