What is Familial Short Stature?

Familial short stature (FSS) is a condition where an individual’s final height as an adult is lower than the third percentile compared to others of their age, sex, and demographic group. However, this height matches the height of their parents, indicating it’s due to family traits rather than conditions like malnutrition, hormone imbalances, or genetic issues. This condition, alongside a delayed growth and puberty phase (known as constitutional delay in growth and puberty, or CDGP), is one of the main reasons for shorter stature.

Another term used in the medical field is idiopathic short stature (ISS), referring to children who are significantly shorter than their peers (by two or more standard “deviations” or differences from the average height for their age, sex, and demographic group), even after other potential causes have been ruled out. Some medical experts consider FSS and CDGP to be subsets of ISS, making a distinction between familial ISS (if it runs in families) and non-familial ISS. Others believe they are different entities. Regardless of how they’re classified, it’s agreed that FSS is a distinct condition where patients achieve an adult height that matches their projected height based their parents’ heights, which is not the case with ISS, where the final height is significantly lower than what would be expected.

While the accepted theory is that a combination of many genes contributes to FSS, this is being questioned, especially in cases where the height is extremely short. As more single-gene defects are being discovered among individuals diagnosed with FSS or ISS (and their family members), this theory is being reassessed. This article summarizes what we know about FSS, the differences amongst CDGP, ISS, and other causes of short height, and updates on recent findings about gene defects that can cause short stature in certain families.

What Causes Familial Short Stature?

Familial short stature (FSS), also known as genetic short stature (GSS), is thought of as a naturally occurring variation in growth, along with constitutional delay of growth and puberty (CDGP). It’s thought to be caused by the combined effects of many genes – a phenomenon referred to as polygenic inheritance, but this is not yet completely confirmed. FSS may also be due to the mother’s physical limitation or short height.

When a family has a history of extremely short stature – meaning a height that’s more than three standard deviations below average for a person’s age, gender, and population group – it’s important to consider and look into the possibility of genetic defects being the cause.

Risk Factors and Frequency for Familial Short Stature

Short stature in children can be caused by various factors. About one-fifth of all cases are due to problems like poor nutrition, chronic diseases, genetic issues, hormonal disorders, and treatments involving certain medications and radiation. However, the majority (four-fifths) of short stature cases are seen as normal variations in growth, and are usually split between Familial Short Stature (FSS) and Constitutional Delay of Growth and Puberty (CDGP).

In a study conducted in Utah, of 555 children with short stature, about 18 percent of boys and 16 percent of girls had a combination of FSS and CDGP. Another study reported that 40 percent of CDGP cases also had FSS.

A noteworthy point is that FSS doesn’t discriminate – it’s found across all races, regions, and genders equally.

Signs and Symptoms of Familial Short Stature

Familial short stature (FSS) is a condition where individuals grow at a slower pace, but still develop normally and are otherwise healthy. This might be determined by taking a family and birth history – if a child was of normal size at birth and their parents are also short, this could indicate FSS. Such children will enter puberty at a normal range, but will grow at a slower pace.

Impressively, an FSS diagnosis could also coexist with a condition called delayed growth puberty (CDGP). In such instances, the short stature might be more noticeable and puberty may occur later than their peers. Growth in these situations often takes longer, extending into the later teenage years.

Interestingly, a recent study noticed a distinct pattern in growth trends. Kids with idiopathic growth hormone deficiency (IGHD) and those with a combination of FSS and CDGP showed their most significant height differences in the early years of life compared to their peers. So, documenting heights over time could help detect these conditions earlier.

A nutritional analysis and medication history can also be informative. Children with FSS generally show normal appetite and weight for their age. However, some medications such as steroids, or treatments like radiation therapy, can impact growth.

Physicians use a variety of measurements to track growth and compare it to standard charts. Things like height, weight and head circumference can all provide valuable information. One significant detail to keep in mind: the transition from measuring an infant’s length to a child’s height can mark a small discrepancy.

  • Birth history
  • Family history
  • Growth velocity
  • Puberty onset
  • Nutritional assessment
  • Medication and treatment history
  • Regular measurements

To identify the possible causes of short stature, doctors perform a careful physical examination looking for any abnormal features. This could help rule out genetic conditions that might result in short stature and identifiable syndromic features. Likewise, it’s worth noting that some children with FSS may have subtle features of specific genetic disorders, which would lead to a revised diagnosis.

Testing for Familial Short Stature

If a child is notably shorter than others their age and their family has a history of short stature or late puberty, they may have familial short stature (FSS). This condition is usually diagnosed by examining the child’s medical history and their current physical health. In some cases, the child may hit puberty later than usually expected due to a condition known as constitutional delay of growth and puberty (CDGP). This delay in conjunction with FSS might result in the child being much shorter than typical FSS cases.

In such cases, the doctor might suggest a bone age (BA) estimation. This is a test where the child’s non-dominant hand is x-rayed and compared to standard tables of bone development. Usually, in FSS patients, their bone age equals their actual age.

If a child is far shorter than usual FSS patients, even if the short stature runs in their family, the doctor might suggest additional tests. This is done to eliminate other potential causes of the short stature. This becomes particularly important in cases where the patient might have partial growth hormone deficiency (GHD). Since GHD is difficult to distinguish from FSS, individualized growth syndrome (ISS), or CDGP, the doctor has to rely on their judgment.

Some possible tests that might be recommended to rule out other causes include tests for blood count, albumin in the blood, thyroid function, insulin growth factor and growth hormone levels, kidney and liver function, calcium and phosphorus levels, anti-gliadin and anti-endomysial antibodies. Karyotyping might also be performed to detect conditions like Turner syndrome that can cause short stature. Other special genetic tests might be conducted in rare FSS cases to rule out hormone-related issues.

Treatment Options for Familial Short Stature

If a child is diagnosed with familial short stature (FSS), which means they’re shorter than average due to hereditary factors, a team will come together to support the child and their family and to explain what outcomes to expect. It’s vital to set realistic expectations about the child’s potential growth.

There’s been some research into the use of a type of medication called recombinant growth hormone (rGH) to increase the height of children with FSS. One study found that the medication did slightly improve the child’s final height, but the difference was minimal. Furthermore, the significant costs and potential risks associated with long-term use of rGH led the researchers to determine that it may not be worth it.

Only a couple of studies have compared the effectiveness of growth hormone treatment in children with FSS versus those with short stature due to non-familial causes. According to these studies, growth hormone treatment is less effective in the FSS group. Overall, the research on rGH therapy for short stature, including FSS, has several limitations. These studies often have too few participants, they lack comparison groups, they use different doses of rGH, and they include undiagnosed conditions that could be causing the short stature.

Given the lack of clear evidence showing the benefits of rGH for FSS, coupled with high costs and unpredictable outcomes, the FDA has not approved this treatment. Any use of growth hormone for FSS should be considered as “off label,” which means it has not been approved by the FDA for this specific use. On the other hand, Recombinant IGF1, another type of treatment, is useful in treating short stature due to IGF1 deficiency caused by specific gene mutations or deletions.

In addition to medical interventions, it’s essential to consider the emotional well-being of children with FSS. Teasing, bullying, and discrimination may lead to psychological challenges. However, one large study called the Wessex growth study disputed the idea that all children with short stature experience these challenges. This study examined children living in their communities whose only health issue was short stature and found no increased cognitive, psychosocial, or maladaptive dysfunction related to their stature.

The key condition that often presents similar symptoms and appears like familial short stature (FSS) is called CDGP. Kids with CDGP are usually born a normal weight and height, like those with FSS, but after a period of slow growth, their speed of growth returns to the standard rate. Unlike FSS kids, however, CDGP kids mature later, their bone age is delayed by at least two years, and they ultimately reach a much taller height than kids with FSS.

Looking at the speed of growth, or height velocity, can help tell these conditions apart:

  • Normal speed of growth: Could be familial short stature or CDGP
  • Slow speed of growth: Could indicate a growth hormone deficiency
  • GSS: Here, the final height is below the 3rd percentile
  • CDGP: The final height reached is within the normal range

Most children who are born small for their gestational age (SGA) will catch up in terms of height and weight by the time they are two years old. Some, however, don’t catch up and continue to be shorter than average. Such cases can be understood by taking a detailed account of their history.

There are other syndromes like Turner, Noonan, and Russell-Silver that may also cause proportionate short stature. These can be distinguished from FSS and each other by taking note of various physical symptoms and conducting specific investigations.

Kids with FSS are well-nourished and active, so they can be easily separated from those with malnutrition, where weight is more impacted than height.

Chronic illnesses have their own specific features that make them different from FSS. Some children might have short stature due to hypothyroidism, but this can be confirmed by conducting thyroid function tests. Cushing syndrome, while a rare cause of short stature, can be uncovered by examining specific physical symptoms, delayed bone age, rate of growth, and results of laboratory tests.

If a child has classical growth hormone deficiency, there are particular physical characteristics, symptoms of other hormone deficiencies, a significant delay in bone age, very noticeable short stature, and poor responses to growth hormone stimulation tests.

If growth hormone deficiency is partial or incomplete, distinguishing it from FSS or CDGP becomes more challenging. Specific stimulation tests aren’t sensitive enough to draw a clear conclusion in such cases.

For teens who haven’t yet hit puberty – boys older than 11 years and girls older than 10 years – it’s important to prime with sex steroids before commencing growth hormone stimulation studies. Otherwise, some children might be wrongly diagnosed with growth hormone deficiency and unnecessarily treated with rGH therapy. The response to stimulation significantly changes when sex-steroid priming is used – either 2 mg of 17-beta-estradiol (for both boys and girls) orally two days before the test, or testosterone (for boys) 50 mg intramuscularly a day before the procedure. It’s also important to note that obesity tends to blunt growth hormone responses to stimulation testing.

What to expect with Familial Short Stature

Kids who have a condition known as familial short stature (FSS) will grow to the height predicted by their parents’ heights. However, compared to others in their age group, gender, and community, they will still be shorter when they reach adulthood.

Possible Complications When Diagnosed with Familial Short Stature

If a wait-and-see approach is taken in Fertility-Sparing Surgery (FSS), there will be no complications. However, it is crucial to identify and address any psychological issues quickly and effectively. If these issues are not managed properly, they can impact the child’s mental health, performance in school, and lower their self-esteem.

Potential Issues:

  • No complications with a wait-and-see approach in Fertility-Sparing Surgery (FSS)
  • Need to quickly identify and address psychological problems
  • Unmanaged psychological issues can impact child’s mental health
  • Unmanaged psychological issues can affect child’s school performance
  • Lower self-esteem

Preventing Familial Short Stature

Teaching families who are dealing with classic familial short stature (FSS) – a genetic condition where short parents have short children – is crucial to prevent unnecessary tests and treatments. It’s essential for these families to understand this genetic link in simple terms.

In cases where children show both FSS and delayed growth (CDGP), the short stature (SS) may be more noticeable. In such cases, families should be advised to undertake tests to rule out any severe health issues that could be causing the short stature.

Additionally, if tests suggest the presence of inheritable disorders that require more comprehensive testing, it’s vital to proceed with those tests.

Occasionally, the assistance of a clinical psychologist may be needed. This professional can provide significant support to the child with FSS and their family, helping them navigate unexpected life situations.

Frequently asked questions

Familial Short Stature (FSS) is a condition where an individual's final height as an adult is lower than the third percentile compared to others of their age, sex, and demographic group. It is due to family traits rather than conditions like malnutrition, hormone imbalances, or genetic issues.

Familial Short Stature is found across all races, regions, and genders equally.

Signs and symptoms of Familial Short Stature (FSS) include: - Slower growth pace: Individuals with FSS grow at a slower pace but still develop normally and are otherwise healthy. - Family and birth history: If a child was of normal size at birth and their parents are also short, this could indicate FSS. - Normal puberty onset: Children with FSS enter puberty at a normal range, but their growth continues at a slower pace. - Delayed growth puberty (CDGP): FSS can coexist with CDGP, where short stature is more noticeable and puberty may occur later than peers. Growth in these cases often extends into the later teenage years. - Distinct growth patterns: A recent study found that children with idiopathic growth hormone deficiency (IGHD) and those with a combination of FSS and CDGP show significant height differences in the early years of life compared to their peers. - Normal appetite and weight: Children with FSS generally have normal appetite and weight for their age. - Impact of medications and treatments: Some medications like steroids or treatments like radiation therapy can impact growth in individuals with FSS. - Measurements for tracking growth: Physicians use measurements such as height, weight, and head circumference to track growth and compare it to standard charts. It's important to note the transition from measuring an infant's length to a child's height can mark a small discrepancy. - Physical examination: Doctors perform a careful physical examination to look for any abnormal features that could help rule out genetic conditions and identify syndromic features associated with short stature. Some children with FSS may have subtle features of specific genetic disorders, leading to a revised diagnosis.

Familial Short Stature is thought to be caused by the combined effects of many genes, a phenomenon referred to as polygenic inheritance. It may also be due to the mother's physical limitation or short height.

The doctor needs to rule out the following conditions when diagnosing Familial Short Stature: 1. Malnutrition 2. Hormone imbalances 3. Genetic issues 4. Constitutional delay of growth and puberty (CDGP) 5. Growth hormone deficiency (GHD) 6. Turner syndrome 7. Noonan syndrome 8. Russell-Silver syndrome 9. Chronic illnesses such as hypothyroidism and Cushing syndrome

The types of tests that might be needed for Familial Short Stature (FSS) include: - Bone age estimation: This test involves x-raying the child's non-dominant hand and comparing it to standard tables of bone development. In FSS patients, their bone age usually equals their actual age. - Blood tests: These tests can help rule out other potential causes of short stature. They may include tests for blood count, albumin, thyroid function, insulin growth factor and growth hormone levels, kidney and liver function, calcium and phosphorus levels, and anti-gliadin and anti-endomysial antibodies. - Karyotyping: This test can detect conditions like Turner syndrome that can cause short stature. - Special genetic tests: In rare cases of FSS, special genetic tests may be conducted to rule out hormone-related issues.

Familial Short Stature (FSS) is typically treated by providing support to the child and their family and setting realistic expectations about the child's potential growth. There has been some research into the use of recombinant growth hormone (rGH) to increase the height of children with FSS, but the effectiveness of this treatment is limited. The use of rGH for FSS is not approved by the FDA and should be considered "off label." Another type of treatment, Recombinant IGF1, is useful in treating short stature due to IGF1 deficiency caused by specific gene mutations or deletions. Additionally, it is important to consider the emotional well-being of children with FSS and address any potential psychological challenges they may face.

The prognosis for Familial Short Stature (FSS) is that individuals with this condition will grow to the height predicted by their parents' heights. However, they will still be shorter compared to others in their age group, gender, and community when they reach adulthood.

Pediatric endocrinologist.

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