A mini module on Short Stature
Cynthia Abraham, BS
Robert Karp, MD
SUNY-Downstate medical Center
Pre-Test (detailed explanations at the bottom):
Q1. Which of the following is the most appropriate component of evaluation of a child with short stature?
a. Medical
b. Nutritional
c. Developmental
d. Social
e. All of the above
Q2. True or False: A height measurement at a single point in time is sufficient to assess for short stature.
Q3. Syndrome causes of short stature include all of the following except:
a. Constitutional delay of growth
b. Precocious puberty
c. Familial short stature
d. Idiopathic short stature
Q4. Which of the following are key components in determining the cause of short stature?
a. Chronological age
b. Bone age
c. Growth velocity
d. All of the above
Q5. How should the height of an 18-month-old child be measured?
a. Standing
b. Supine
c. By measuring arm span and using that as an estimate for height
Q6. When assessing short stature, weight to height ratio is effective in distinguishing which of the pairs listed below?
a. Constitutional delay of growth OR familial short stature
b. Endocrine disease short stature OR malnutrition short stature
Objectives
On completion of this mini-module, residents will be able to:
1. Appreciate patterns of normal growth.
2. Evaluate a child with short stature.
3. Distinguish between non-syndrome causes short stature.
4. Know indications for growth hormone therapy
Facilitator's Preparation
The review by Rose, Vogiatzi, and Copeland in Pediatrics in Review (A general pediatric approach for evaluating the short child), 2005;26:410-420 provided the core material for this mini-module on the healthy child who is shorter than expected. Reader's will want to see the full module of nutrition and Failure to Thrive by Heyman and Frank in the Teacher's Guide; (part IV; Section 2,a) for a complete description of growth failure.
Introduction
Short stature has been mentioned briefly within this mini-module as an adjunct to the formal module on nutritional status in Failure to Thrive - Part IV, Section X.x. However, short stature is not necessarily caused by combinations of disease states, poverty, or neglect. In 1970, Dugdale made the following points through the use of arm anthropometry: children who are short but who have above normal muscle mass and children who are tall but who have below normal muscle mass are both considered to be well-nourished. Quite often the children we see in the clinical setting are often healthy but their linear growth is slow.
The non-syndrome causes of growth failure consist of constitutional delay of growth, familial short stature and idiopathic short stature. Recognizing that there are non-syndrome causes of short stature and distinguishing them from one another may be difficult. Hopefully, this module will be helpful in clarifying the differences between these conditions.
Short Stature and Normal growth
Short stature is defined as height that is two standard deviations or more below the mean height for children of that sex and chronological age. In assessing short stature, a single measurement is less important in assessing growth than a pattern of growth over time.
Here are key points about normal growth. There are three phases of growth: 1) infantile, 2) childhood, and 3) pubertal. During the infantile phase, between birth and 2 years of age, growth occurs at a rate of 25 cm/year. During this phase, it is very common for infants to cross percentile lines as they grow more towards their genetic potential and interact less with the intrauterine environment. The childhood phase is characterized by a growth of 4-7 cm/year while growth in the pubertal phase is quite variable ranging from 8 to 14 cm per year. Growth
velocity curves are extremely important for use with aberrant growth patterns.
Table 1: Normal growth rate from birth to start of puberty
Evaluation
Evaluation of a child with short stature begins with a history. The parents of the child should be asked their heights and those of siblings. Parents should also be asked at what ages they attained their adult heights and whether they recall a late growth spurt. After attaining parents' height, the child's height potential can be predicted by using the following formulas:
GIRLS: 13 cm subtracted from the father's height and averaged with the mother's height
BOYS: 13 cm added to the mother's height and averaged with the father's height
For both boys and girls, 8.5 cm on either side of this value represent the 3rd to 97th percentiles for anticipated adult height.
A review of systems should be done with emphasis on gastrointestinal, cardiac, renal, pulmonary and endocrine systems. A nutritional, developmental and social history should also be recorded. When recording a social history, keep in mind that although ethnic differences do exist, these differences are primarily environmental in origin and do not reflect true biologic or genetic factors that affect height. One should always consider the possibility of child abuse or neglect assessing a child with short stature. Do not, however, assume abuse or neglect. [see module on failure to thrive].
On physical exam, one needs to verify that the child's height is indeed two or more standard deviations below average height. One must also consider the possibility of relative short stature when parents are tall and the child is average height. Measurements should be done in triplicate using a proper measuring board rather than an arm from a scale. For children over the age of 2 years, height should be measured with the child standing (see Fig. 1a). For a child under the age of 2 years, height should be measured with the infant supine (see Fig. 1b). Arm span instead of height should be measured in children with scoliosis or contractures; arm span is approximately equal to height in children 8 years or older. Under the special circumstance of teen pregnancy in which there is collapse of tissues in the spinal column, Scholl (1988) created a special assessment of height using knee-heel length.
Figure 1a./1b. :The correct methods for measuring length and height.
[See Jelliffe pp. 68-69]
After measuring the child's height, one should note the upper segment: lower segment ratio (U/L ratio), presence of dysmorphic features and weight-height ratio. Rose et al. (2006) notes in their review on short stature that a U/L ratio of greater than 1.0 in one who is of short stature is a red flag for achondroplasia or rickets and the presence of dysmorphic features is indicative of diseases such as Down Syndrome and Turner Syndrome. A high weight-height ratio in one who is of short stature may point in the direction of an endocrine disease (growth hormone deficiency, Cushing's, hypothyroidism), a syndrome affecting weight (e.g., Prader Willi) while a low weight-height ratio may direct one to consider chronic systemic diseases (cystic fibrosis, renal disease) or malnutrition. This mini-module on short stature will focus solely on non-syndrome causes of short stature.
Ascertaining the cause of short stature requires determining the child's chronological age (CA), bone age (BA), growth velocity and weight-height ratio in addition to the child's absolute height. The table below shows how determining the relationship between the patient's chronological age and bone age and the patient's growth velocity can help narrow the cause of short stature in a particular patient.
Table 2: Chronological age, bone age, growth velocities and causes of short stature
TEACHING CAPTION: Note that Bone Age is never greater than Chronological Age in a healthy child. It is always pathologic.
Bone age is never greater than chronological age in a healthy child.
Further evaluation of short stature involves lab studies such as a CBC, sweat chloride test (for cystic fibrosis), antiendomysial IgA and IgG (gluten enteropathy), IGF-1 and IGFBP-3 (both for growth hormone deficiency) and thyroid function tests. Growth hormone (GH) levels are not usually done as these levels are variable throughout the day and are pulsatile.
Non-Syndrome Causes of Short Stature
Non-syndrome causes of short stature consist of constitutional delay of growth, familial short stature and idiopathic short stature. Although these entities all lead to short stature, they have different effects on bone age and growth velocity as indicated by the weight-height charts below. The solid lines are normal growth curves at the 5th and 95th percentiles. The dashed lines indicate the growth patterns in those with specific conditions.
FIGURE 2: Identifying growth characteristics of "Constitutional", "Idiopathic", and "Familial" Short Stature
TEACHING CAPTION: Idiopathic short stature is a difficult diagnosis in that parents are of normal height. Patience is an oft-needed quality for assessing these children without creating problems from obsessive testing.
Idiopathic short stature appears similar to familial short stature when height and weight are plotted but family history differentiates the two. In idiopathic short stature, the parents are of normal height. It is, unfortunately, a condition of exclusion requiring more extensive evaluation than constitutional and familial short stature. Quite often, a careful family history will identify a similarly short ancestor. Adopted children present a problem especially if there is early malnutrition. At times, one does not identify a cause and therefore assumes that the short stature is "idiopathic" (e.g., we don't know") in origin. Idiopathic short stature is a difficult diagnosis in that parents are of normal height. Patience is an oft-needed quality for assessing these children without creating problems from obsessive testing.
Figure 3. below, a "Weaver Curve, plots standard deviation from mean height for children vs. the standard deviation from mean height for the parents. This helps clarify the difference between familial and other causes of short stature including idiopathic short stature. The area below the dark line starting at -2 on the y-axis indicates the range at which a child would be considered to be of short stature. The area to the left of the vertical line starting at -2 on the x-axis indicates the range at which an adult would be considered to be of short stature. The linear midparental offspring regression line and the ±2 standard deviations (5 and 95%, respectively) have been plotted on this graph.
FIGURE 3: "Weaver Curve" plotting standard deviation from mean height for children vs. the standard deviation from mean height for the parents. [Derived from Weaver DD, Christian JC. Familial variation of head size and adjustment for parental head circumference. Journal of Pediatrics. 1980;96(6):990-4.]
- If the heights of the child and parent are both two standard deviations or more below the mean but their heights fall in between solid diagonal line and the lower dashed diagonal line, one should consider familial short stature.
- If the heights of the child and parent are both two standard deviations below the mean BUT their heights fall below the lower diagonal line, one must consider familial short stature combined with another disease entity that is also contributing to the short stature. Possibilities for the other disease include malnutrition, a chronic systemic disease, an endocrine disease or a chromosomal disorder.
- If the height of the child is two standard deviations below the mean but the parent's height is not, consider all causes of short stature except familial short stature.
Treatment
Treatment of non-syndromic short stature is dependent on etiology. Growth hormone therapy is approved for those children whose expected adult height is less than 63 inches in boys and less than 59 inches in girls in those with idiopathic short stature. Other indications for growth hormone therapy are growth hormone deficiency, growth failure associated with chronic renal insufficiency and short stature associated with Turner Syndrome.
Case Study Part 1
You are a medical student in the general pediatrics clinic and you have received the chart of a 10 year old boy here for a routine physical. When plotting his height you notice that his height at this visit is below the 5th percentile. His weight is at the 5th percentile. You also found that his height has been below the 5th percentile for the past two years. You obtain the following history.
- Medical History: no GI, cardiac, renal, pulmonary symptoms
- Nutritional History: three meals a day (cereal with whole milk, pizza, rice and beans), one snack between lunch and dinner (box of raisins)
- Social History: child lives in two bedroom apartment with parents and younger brother. Mom is a social worker. Dad works in a bank. No problems with heat, ventilation or pests. No loose paint.
- Developmental history: normal; child is doing very well in school.
Q1. What questions would you like to ask the parents?
A1. When assessing a child who is of short stature, it is important to
ask the parents how tall they are and at what ages they achieved their present heights. One could also ask how tall the patient's siblings are as well. Based on the parent's heights, one should calculate the child's predicted height.
Q2. What parameters of growth would you like to assess?
A2. Three parameters of growth that are very important in
assessing a child with short stature are chronological age, bone
age and growth velocity. See table #2 in this module for how
these three parameters are affected in different non syndrome
causes of short stature.
Case Study - Part 2
Mother is 5'3". Father is 5'10." Mother attained adult height at 16. Father attained adult height at 22. The child's predicted height is 5'6" - 6'0" When the child's growth was plotted, growth velocity was found to be normal. When bone imaging was performed, it was found that his bone age lagged behind his chronological age.
Q3. What is your diagnosis?
A3. Based on the normal growth velocity and lag of bone age behind chronological age, one can conclude that this patient is demonstrating constitutional delay of growth. The normal heights of the parents and the late ages at which they attained these heights also support this diagnosis.
Q4. What advice would you give to the child and parents?
A4. Tell the parents that the child is growing at a normal rate. Based on family history and imaging, this child will continue to grow
below the 5th percentile until puberty at which point the child will
experience a growth spurt. At this point, the child will most likely be of normal height. However, puberty may occur late based on parental history.
Questions
Q1. How should the height of an 18 month old child be measured?
a. standing
b. supine
c. by measuring arm span and using that as an estimate for height
Q2. For which of the following is growth hormone therapy approved:
a. constitutional delay of growth
b. familial short stature
c. malnutrition
d. none of the above
Q3. All of the following lab tests should be obtained in one with short stature except:
a. CBC
b. GH
c. IGF-1, IGFBP-3
d. Thyroid function tests
e. Sweat chloride test
Q4. When assessing short stature, weight to height ratios differentiate between what causes of short stature?
a. constitutional delay of growth, familial short stature
b. endocrine diseases, malnutrition
c. familial short stature, idiopathic short stature
Answers
A1. The answer is B. Children below the age of 2 years must be measured supine. Children over the age of 2 years must be measured standing. Those with contractures or scoliosis should have their arm span measured as an estimation of height.
A2. The answer is D. Growth hormone therapy is approved for the following entities: growth hormone deficiency, growth failure associated with chronic renal insufficiency and short stature associated with Turner or Prader-Willi syndromes. Growth hormone therapy is also approved in those with idiopathic short stature whose expected adult height is less than 63 inches in boys and less than 59 inches in girls.
A3. The answer is B. Growth hormone is not a good test for assessing short stature because measurements of growth hormone are highly variable due to its pulsatile release. IGF-1 and IGFBP-3 are better surrogates for assessing growth hormone deficiency and are more sensitive. A CBC should be done in order to rule in or rule out any hematological causes of short stature. Thyroid function tests should be done in order to rule in or rule out hypothyroidism which can manifest as short stature with a high weight-height ratio. A sweat chloride test is done to rule in or rule out cystic fibrosis which can cause malabsorption.
A4. The answer is B. In endocrine causes of short stature, the weight-height ratio is high. In malnutrition, the weight-height ratio is low. Family history and bone age differentiate constitutional delay of growth from familial short stature. Family history differentiates familial short stature from idiopathic short stature.
References
Dugdale AE, Chen ST, Hewitt G. Patterns of growth and nutrition in childhood. Am J Clin Nutr. 1970;23(10):1280-7.
Jelliffe, DB. The assessment of the nutritional status of the community. World Health Organization Monograph no. 53 WHO. Geneva, 1966.
Kapr RJ, Scholl TO, Decker E, Ebert E. Growth of Abused Children. Contrasted with the Non-abused in an Urban Poor Community. Clinical Pediatrics. 1989;28(7):317-20.
Rose SR, Vogiatzi MG, Copeland KC. A general pediatric approach for evaluating the short child. Pediatrics in Review. 2005;26:410-420
Scholl TO, Hediger ML, Ances IG, Cronk CE. Growth during early teenage pregnancies. Lancet. 1988;1(8587):701-2.
Scholl TO, Karp RJ, Theophano J, Decker E. Ethnic Differences in Growth and Nutritional Satus: a Study of Poor School Children in Southern New Jersey. Public Health Reports. 1987;102(3):278-83.
Weaver DD, Christian JC. Familial variation of head size and adjustment for parental head circumference. Journal of Pediatrics. 1980;96(6):990-4.
Annotated Pre-test Answers
A1. The answer is E. A medical history must be taken with emphasis on GI, cardiac, renal, pulmonary and endocrine systems. Inflammatory bowel disease, chronic renal disease, cystic fibrosis and hypothyroidism are just a few of the causes of the short stature. A nutritional history should be taken, as malnutrition is a major cause of short stature. A developmental history should be recorded to look for any developmental abnormalities that could run in conjunction with Short Stature (i.e. Prader-Willi). Malnutrition can also cause developmental delays. A social history should be performed in order to assess for factors (i.e., poverty, stresses on family or inappropriate parenting) that could adversely affect a child's growth.
A2. The answer is False. A key factor in assessing the cause of short stature is determining the growth velocity, which cannot be determined with a measurement at a single point in time.
A3. The answer C. Precocious puberty may leave a teen smaller, but it does not present with short stature in childhood. Rather they are tall early with presence of pubic hair and breast development in girls and penile enlargement in boys. On the other hand, those with constitutional delay of growth, familial short stature and idiopathic short stature only present with short stature.
A4. The answer is D. All of these are important in the evaluation See Table 2, below.
A5. The answer is B. Children below the age of 2 years must be measured supine. Children over the age of 2 years must be measured standing. Those with contractures or scoliosis should have their arm span measured as an estimation of height.
A6. The answer is B. In endocrine causes of short stature, the weight-height ratio is high. In malnutrition, the weight-height ratio is low. Family history and bone age differentiate constitutional delay of growth from familial short stature. Family history differentiates familial short stature from idiopathic short stature.
