Short StaturePresented by-

Dr. Deepali Jain

GUIDED BY-

Dr. Deepak Dwivedi

References

1. Nelson Textbook of Pediatrics

2. Pediatric Endocrinology, Fifth edition Vol. 2

3. Practical strategies in Pediatric diagnosis and therapy

4. O. P. Ghai, 8th edition

5. Pubmed

IntroductionGrowth is the fundamental physiologic process that characterizes childhood.

Secular trends in growth patterns are followed as indicators of children’s health on a population level.

Growth can be worrisome along two variables: height (short stature) and velocity (growth failure).

Definition of Short Stature

• Height less than the 3rd percentile or 2SD below the mean for age of the population reference standard.

• Excessively short i.e. more than 2 SD below the Mid-Parental Height (MPH) or Target height (TH) even if the height recorded is within the normal population percentiles for age.

• Growth velocity less than 25th percentile on a velocity curve over a period of 6-12 months.

• Dwarfism refers to more severe short stature, defined as height below 3 SD for age & gender norms.

Growth Velocity

• Growth velocity =

𝐻𝑒𝑖𝑔ℎ𝑡 𝑐𝑚 𝑎𝑡 𝑡𝑖𝑚𝑒2―𝐻𝑒𝑖𝑔ℎ𝑡 𝑐𝑚 𝑎𝑡 𝑡𝑖𝑚𝑒1

𝑇𝑖𝑚𝑒2−𝑇𝑖𝑚𝑒1(𝑚𝑜𝑛𝑡ℎ𝑠)× 12(months/year)

• Thus, abnormally slow growth velocity, or height dropping across two major centile lines on the growth chart are the two other definitions of worrisome growth.

Significance• The Social Problem –

Short stature is a cause of psychosocial stress, and the extent to which this is a problem depends on the severity of the height deficit, the degree of tolerance in the local population, and the child’s coping skills.

• The Medical Problem –

Multiple diseases can present solely with growth failure, such as celiac disease, inflammatory bowel disease, cystic fibrosis, renal tubular acidosis, and human immunodeficiency virus (HIV) infection.

Although girls werereferred to an

academic growth center less often andwith greater height

deficits than the boys, a significantly

higher percentage of the girls had underlying

pathology that requires intervention

The distribution of each major diagnosticcategory for (A) boys and (B) girls referred to an academicGrowth Center in 2001.

Normal patterns of Growth

• Fetal Growth & Birth size –

Reflects mainly maternal factors –

maternal or uterine size,

parity and multiparity,

nutrition, and uteroplacental blood flow

small effect of congenital disorders on prenatal growth

• Postnatal Growth –

The rate of linear growth is greatest in infancy

genetic or familial influences begin to exert their effect on height

Growth velocityYEAR INCREMENT (in cms)

1 25

2 10

3,4 7

5,6 6

7 – Puberty 5

Mid - puberty 9 – 10.3

Growth accelerates

again at puberty.

The timing of the

pubertal

growth spurt differs

between girls and boys.

Etiology of Short statureNormal variants –

1. Constitutional growth delay

2. Genetic/ Familial Short stature

3. Combined

Pathological –

1. Nutritional

i. Macronutrient deficiency

ii. Micronutrient deficiency

Decreased intake – kwashiorkor;anorexia nervosa

Decreased absorption – inflammatorybowel ds.;celiac ds.;

cystic fibrosis; malabsorption

Etiology of Short stature

2. Endocrinal causes – Hypothyroidism; Isolated GH deficiency; Hypopituitarism; Glucocorticoid excess; Precocious puberty

3. Chromosomal defects – Turner; Down syndrome; Praderwilli syndrome

4. LBW short stature – Sporadic; Russell Silver syndrome; Cornelia de lange syndrome; Bloom syndrome

5. Defects in Bone development – Achondroplasia; Chondrodystrophies

Etiology of Short stature

6. Metabolic causes – Mucopolysaccharidosis; other storage disorders

7. Chronic diseases – Chronic Liver ds.; Chronic renal ds.; Chronic infections; CHD; Poorly controlled Diabetes Mellitus

8. Psychosocial deprivation

9. Chronic drug intake – Glucocorticoids; High dose estrogens & androgens; Methylphenidate; Dextroamphetamines

Assessment of Short stature

1. Accurate height measurement

2. Assessment of height velocity

3. Comparison with population norms

4. Comparison with child’s own genetic potential

5. Assessment of body proportion

6. Sexual maturity rating

7. Bone age

Accurate height measurement• <2 years: supine length; infantometer

• >2 years: standing height ; stadiometer

• Bulky diapers removed

• Child is placed supine on the infantometer

• Head held firmly against a fixed upright head board by one person

• Legs straightened, feet at right angles to legs

Accurate height measurement• Without footwear

• Heels, buttocks, scapulae and occiput

touching the wall

• Lower border of the eye socket in the same

horizontal plane as external auditory meatus

( FRANKFURT PLANE)

• Looking straight ahead

• Gentle but firm pressure upwards applied to

the mastoids from underneath

• A Harpenden stadiometer which determines height accurately (within 0.1 cm) is the most sophisticated instrument.

Assessment of Height velocity

YEAR INCREMENT (in cms)

1 25

2 10

3,4 7

5,6 6

7 – Puberty 5

Mid - puberty 9 – 10.3

• Rate of increase in height over a period of time expressed as cm/ yr.

• All pathological causes of short stature will cause a poor growth velocity.

Comparison with population norms

• The height should be plotted on appropriate growth charts.

• Any child who falls behind in growth across major percentiles in the chart should be evaluated, even when the height is not below the third percentile.

• Use any chart but adjust for mid-parental height.

Examples of Growth charts –

1. IAP (IAP Growth Monitoring guidelines 2007)2. WHO (MGRS Study 2006)3. CDC 4. British 20055. ICMR6. 1989 Affluent Indian

(Agarwal et al)7. 2009 Affluent Indian

(Khadilkar et al)

Comparison with child’s own genetic potential

• Mid parental height (MPH) gives an estimate of the child’s genetically determined potential.

MPH for boys =𝑀𝑜𝑡ℎ𝑒𝑟′𝑠 +𝐹𝑎𝑡ℎ𝑒𝑟′𝑠 ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)

2+ 6.5 cm

MPH for girls =𝑀𝑜𝑡ℎ𝑒𝑟′𝑠+𝐹𝑎𝑡ℎ𝑒𝑟′𝑠 ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)

2- 6.5 cm

• The target height obtained by this method is then applied to the 20-year line of the gender-appropriate growth chart.

The projected height is determined by

extrapolating the child’s growth along his or her own channel. If

the projected final height is within 5cm of the midparental target

height, the child’s height is appropriate

for the family

Assessment of Body proportion

Proportionality is assessed by –• Upper segment : Lower segment Ratio

• Comparison of arm span with height

Based on this, short stature can be

• Normally US : LS Ratio –

Birth: 1.7

3 years: 1.3

6 years: 1.1

10 years: 1

Adults: 0.9

Proportionate

Disproportionate

• Increase in US : LS ratio –

- Rickets

- Achondroplasia

- Untreated Congenital Hypothyroidism

• Decrease in US : LS ratio –

- Spondylo-epiphyseal dysplasia

- Vertebral anomalies

• Conditions that adversely affect the vertebrae, such as scoliosis or irradiation, may result in growth retardation and disproportionately long arms.

• In case of disproportionate short stature,

further measurements of the various limb

segments should also be made.

Normally, SE/EMC = 1

Rhizomelia = 0.98

Sexual Maturity Rating (SMR)

• SMR stage should be assessed in older children.

Short stature:

precocious puberty due to early epiphyseal fusion.

Delayed puberty as growth spurt is delayed.

Skeletal Maturation

• The pattern of skeletal maturity is also helpful in differentiating the type of short stature.

• BONE AGE - method of assessing skeletal maturity observed directly by visualization of epiphyseal growth plates on X-ray.

• X-rays useful to determine skeletal age –

1. <1 year: shoulder x-ray

2. 1-13 years: hands and wrists

3. >13 years: elbow and hip

• Bone age is necessary:

- in the diagnosis of FSS and CGD;

- for interpreting hormone levels in pubertal age;

- for diagnosis of precocious puberty or hyperandrogenism;

- for deciding whether to treat or not the above mentioned conditions;

- for predicting adult height in normal children;

- in evaluating any child with growth and/or puberty disorders;

- in deciding the time to start replacement therapy in hypogonadism;

- in monitoring children on growth hormone therapy.

Methods for bone age evaluation

1. Greulich & Pyle method - In their method for each of these bones an elaborate description of its developmental stages is included.

2. Tanner and Whitehouse method - It is based on a set of bone’s standard maturity for each age population.

3. Roche–Wainer–Thissen – The five predictor variables in the RWT method are recumbent length, weight, bone age, chronological age, and parental heights.

Computer programs have been developed for the calculation of both mid-parental target heights and predicted adult heights (by all three methods).

Evaluating a child with short statureHistory –

Maternal History

Birth History

Growth pattern

Developmental milestones

Family History

Dietary History

Medical History

Physical Examination –

• Measurements: weight, standing height, sitting height, head circumference.

• Height in relation to previous heights (height velocity), parents’ heights, stage of puberty, weight.

• Genitalia and pubertal development

• Body composition: subcutaneous fat and muscle bulk

• Unusual or dysmorphic features

• Signs of specific diseases

History and Presentation

• Hypoglycemia, prolonged - Congenital GH deficiencyjaundice, small penis

• Antenatal - IUGR• Puffy extremities - Turner syndrome• Fever, weight loss, - Chronic infections

anorexia• Chronic diarrhoea/ - Malabsorption

bulky frothy stools• Dyspnea, cough, cyanosis - Systemic diseases• Headache, vomiting, - Pituitary or hypothalamic SOL

diplopia• Polyuria - CRF, RTA• Weight gain, obesity - Cushing syndrome• Constipation, lethargy, - Hypothyroidism

delayed milestones

Clues on Examination• Pallor - Anemia• Hypertension - CRF, Cushing syndrome• Dysmorphism - Genetic disorders• Midline defect - Hypopituitarism• Vitamin deficiency, - Malabsorption, PEM

Wt for Ht• Frontal bossing, - Congenital GH deficiency

depressed nasal bridge• Disproportionate body - Skeletal dysplasia, Rickets

proportion• Central obesity, - Cushing syndrome

proximal weakness• Papilloedema, visual defect, - Pituitary Tumor

optic atrophy• Goiter, delayed dentition, - Hypothyroidism

Short lower limbs

APPROACHMeasurement

Normal Abnormal

Clues H/O & EXAM

Present Absent

Assess growth rate & bone age

<4 cm/yr >4 cm/yr

Bone age Bone age

delayed normal normal delayed

do screenning inv. Genetic ds GSS CGD

Stepwise investigative work - up• Level-1 investigations –

1. CBC

2. CRP & ESR

3. Urinalysis

4. Stool examination

5. S. Electrolytes

6. Liver and Renal

function tests

7. Bone age

• Level-2 investigations –

1. Thyroid function tests

2. Karyotyping

3. Prolactin

4. Neuroimaging

• Level-3 investigations –

1. Coeliac serology & duodenal biopsy

2. GH stimulation test & serum IGF-1 levels

Differential Diagnosis

• Variants of Normal

– Familial short stature

– Constitutional delay

• Pathologic/Growth Failure

– Endocrinal

– Genetic

– Systemic

– Psychosocial

Familial/Genetic short stature• Birth weight and length below 3rd percentile for GA

• Although the growth channel is low,

it parallels the normal growth curve.

• Family history of short stature

• Normal onset of puberty

• Bone age appropriate for

chronological age

• The adult height is likely to be shorter

than average.

Constitutional growth delay• The most common cause of

short stature and sexual

infantilism in the adolescent.

• Delayed onset of puberty

• A late adolescent growth

spurt (Late Bloomers)

• Final height is normal

• Bone age delayed

A positive family history of delayed but normal puberty and growth, a normal sense of smell (to exclude Kallmann syndrome), and normal

neurologic findings favor constitutional delay.

Intrauterine Growth Retardation

• Small for gestational age at birth

• Slow growth from early infancy

• Normal bone age,sexualdevelopment

• Normal GH levels

• Normal growth pattern in family

• Serum IGF-1 levels were lower,

and GH levels higher

• Higher basal and stimulated

suggested GH resistance

IUGR infant who maintains normal growth rates but does notexhibit catch-up growth.

Growth hormone deficiency

• Congenital -

-idiopathic

-associated with midline defects (absent septum pellucidum, optic nerve hypoplasia [septooptic dysplasia], cleft palate, holoprosencephaly, single central incisor)

-defects in the genes for GH

• Acquired –

-birth injury

-head injury

-cranial irradiation

-craniopharyngioma

• Growth hormone insensitivity (Laron syndrome)

• Clinical features –- Normal birth size

- Mid-facial crowding

- Round cherubic facies

- Depressed nasal bridge

- Micropenis

- Frontal bossing

- Heightage < weight age

- Neonates – hypoglycemia/

prolonged jaundice

- Bone age is delayed

- Body proportions are normal

• Lab. Diagnosis –- subnormal GH levels (<7 or 10 ng/mL)

in response to two pharmacologic

stimuli (clonidine, arginine,

insulin-induced hypoglycemia).

- Low IGF-1 and IGFBP3.

- Neuroimaging for acquired causes.

• Treatment –- Replacement therapy with hGH.

- Recommended dose of hGH is

0.18-0.3 mg/kg/wk. It is administered

subcutaneously in seven divided doses

until near final height is achieved.

Hypothyroidism

• May be congenital or acquired

• Clinical features –- Prolongation of physiologic icterus

- Birth size normal

- Feeding difficulty, sluggishness

- Large tongue, large abdomen

- Poor appetite

- Umbilical hernia

- Cold & mottled extremities

- Wide open ant. & post. Fontenelle

- Short stature, Bone age delayed

- Myxoedema

- Dry skin, delayed puberty

A.Congenital hypothyroidism in an infant6 mo of age

B.Four mo after treatment, decreased puffinessalert appearance

Lab. Diagnosis –-Newborn screening for congenital Hypothyroidism is routine - If abnormal repeat- Elevated serum TSH and low T4.- Positive TSH receptor-blocking antibodies- diagnosis for transient congenital Hypothyroidism- If normal TSH & low T4, look for Pituitary or hypothalamic cause- Thyroid antibodies (antithyroglobulin, antimicrosomal antibodies) is consistent with autoimmune thyroiditis.

Treatment –-In neonates, the initial starting dose is 10-15 μg/kg.- Children with hypothyroidism require about 4 μg/kg/24 hr.- Monitoring of free T4 (or FTI) and TSH is essential for optimizing the dose of medication.- Educate parents and child about disease.

Achondroplasia• Most common osteochondrodystrophy.• caudal narrowing of spinal canal• Autosomal dominant disease.• But there are studies present which

shows the germline and somatic mosiacismin achondroplasia

[J Med Genet 2000;37:956-958 doi:10.1136/jmg.37.12.956].

• Treatment –

- Counselling of parents- Dietary advice- Psychological counselling- Annual monitoring of height and weight- Drugs: GH

Turner syndrome- classic form being 45,XO

- progressive deviation of height

away from the normal growth curve

- Streak gonads

- small birth size and dysmorphic

features

- Abnormally high levels of the

gonadotropins, LH, FSH

Treatment –• GH therapy

• sex steroid replacement therapy

Psychosocial Dwarfism/ HyperphagicDwarfism

• Profound short stature without

apparent malnutrition.

• Characterized by functional

hypopituitarism.

• Low IGF-1 levels & inadequate

response to GH stimulation.

• Less stressful environment

is beneficial.Between ages 6 and

8 years, he had chemicalevidence of growth hormone (GH)deficiency. B, After placement in a

chronic care facility (arrow), hisgrowth rate improved markedly, and

his GH levels reverted to normal.

Take Home Message

• Take height by proper method and plot it on appropriate growth chart.

• Use Growth Charts appropriately.• Every child must have proper growth monitoring so as to know

whether the child is on his proper road to growth.• Any child with short stature is not always familial and should

evaluated completely.