Abnormalities in the short stature homeobox-containing (SHOX) gene cause SHOX syndrome. This condition leads to a short stature and other skeletal differences that develop in the first few years of life.
The SHOX gene plays an important role in bone growth and development, particularly that of the long bones in the arms and legs.
A note about sex and gender
Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.
There is one copy of the SHOX gene on each of the sex chromosomes, also called the X and Y chromosomes. The gene is located at a part of the chromosome called the pseudoautosomal region. This means that people have two functional copies of the SHOX gene in each cell.
SHOX syndrome, also called SHOX deficiency, can occur due to the following:
- a change or “mutation” in one of the SHOX genes
- a loss or “deletion” of one of the SHOX genes
- a deletion of both SHOX genes
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If a parent has a SHOX deficiency disorder, they have a 50% chance of passing on the related SHOX gene variant to their offspring. If both parents have SHOX deficiency, their offspring has the following:
- a 50% chance of developing SHOX deficiency disorder
- a 25% chance of developing a SHOX-related condition called Langer mesomelic dysplasia
- a 25% chance of developing neither of the above conditions
According to the Genetic and Rare Diseases Information Center, SHOX deficiency most often results in short stature. The medical term for this is SHOX-related short stature.
As well as short stature compared with children of the same age and sex, symptoms typically include:
- shortened forearms and legs
- elbows that are turned outward
- knees that are turned inward
- bowing of the shinbones
- short feet
- a short neck
- a small lower jaw
- atypical curvature of the spine
- abnormalities involving the bones of the wrists and forearms
- a high palate, meaning the roof of the mouth is high and narrow
- increased muscle mass
Associated conditions
Individuals with SHOX deficiency may show additional signs and symptoms, depending on the type of SHOX-related condition they have:
| Condition | Who it affects | Signs and symptoms |
|---|---|---|
| Langer mesomelic dysplasia (LMD) | Males and females | • very short stature • mesomelia, which is extreme shortening of the long bones in the arms and legs • Madelung deformity, which is an abnormality affecting the bones of the wrists and forearms |
| Léri-Weill dyschondrosteosis | Males and females | Similar to those of LMD, but less severe |
| Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (type 1) | Females | • absence or underdevelopment of the vagina and uterus • absence of menstruation by age 16 • painful intercourse |
| MRKH syndrome (type 2) | Females | • absence or underdevelopment of the vagina and uterus • absence of menstruation by age 16 • abnormal kidney development or positioning • spinal abnormalities • hearing loss • heart defects |
| Turner syndrome | Females | • short stature • skeletal abnormalities, such as unusual rotation of the wrist and elbow joints • reduced ovarian function • lack of female sex hormones • absent puberty • extra folds of skin on the neck • a low hairline at the back of the neck • swelling of the hands and feet • kidney problems • heart defects |
A doctor may suspect SHOX deficiency if a child shows evidence of short stature or limited growth without any obvious cause. X-rays of the hands and wrists may help doctors identify bone changes associated with the condition.
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Finally, genetic tests can confirm a diagnosis of SHOX syndrome.
Doctors may recommend genetic counseling for individuals with suspected or confirmed SHOX syndrome and their families.
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Once a person has undergone genetic testing, they may return to their genetic counselor to learn more about their test results and treatment options and to voice any concerns they have. The counselor can also refer the person to other healthcare providers and support groups.
The National Society of Genetic Counselors directory offers access to over 3,300 genetic counselors in the United States and Canada. Users can specify whether they require in-person counseling or telehealth counseling via phone or video.
The American College of Medical Genetics and Genomics directory shows the locations of genetics clinics across the U.S. and allows people to search by location.
According to a
In most cases, HGH therapy can increase the child’s final height by around
Doctors may also recommend the following treatments to help alleviate wrist pain and discomfort in children with painful Madelung deformity in both wrists:
- wrist splints and supports
- ergonomic devices, such as computer keyboards
- limiting certain activities, such as:
- lifting
- gripping
- writing
- typing
- sports that strain the wrist
A 2022 case series report highlights the importance of diagnosing SHOX deficiency as early as possible, stating that HGH therapy is most effective when a person starts receiving it at a young age.
To help speed up diagnosis, the report recommends genetic testing for individuals with the following:
- clinical signs of SHOX deficiency
- radiological signs of SHOX deficiency
- a family history of short stature
There is very little information on whether SHOX deficiency affects life expectancy.
A genetic mutation or deletion affecting the short stature homeobox-containing (SHOX) gene causes SHOX syndrome, also called SHOX deficiency. This gene plays an important role in bone growth and development, and SHOX syndrome primarily causes short stature and other skeletal differences.
SHOX deficiency is involved in various conditions, some of which may cause additional symptoms, such as absent puberty, abnormal kidney development, and heart defects.
Doctors may use a combination of X-rays, human growth hormone (HGH) stimulation tests, and genetic tests to confirm SHOX deficiency. The primary treatment is HGH therapy to help increase final height, though doctors may recommend additional treatments to address other symptoms.
Because SHOX deficiency is a heritable disease, doctors may also recommend genetic counseling for affected individuals and their family members.
