Joan Di Martino-Nardi, M.D. of Westchester Health Pediatrics discusses short stature and poor growth in children.

1. Short Stature and
Poor Growth
Joan Di Martino-Nardi, M.D.
Westchester Health Associates
Pediatrics
March 31, 2016

2. Joan Di Martino-Nardi, M.D.
• Investigator
oNovoNordisk
• Speaker’s Bureau
oNovoNordisk
oGenentech

3. Objectives
• Review Normal growth
• Identify the children who should be evaluated for short stature or
poor growth
• Understand the causes of short stature/poor growth
• Review Growth Hormone and IGF-1 physiology
• Outline Evaluation

5. Height Prediction
-Based upon bone age and
Height at the time bone age is
obtained
-Bayley-Pinneau method is the
most accurate method (± 2
inches)
(plot height for bone
age)
Height for bone age
Predicted height
Height for Chronological
age

6. Genetic Potential: Target Height
Height Prediction should be = Target Height
Target height = Midparental height ± 5 cm ( 2 inches)
Midparental height for Males:
{mother’s height + 5 inches} + father’s height
Midparental height for Females
{father’s height – 5 inches} + mother’s height
2
*13 cm=5 inches

7. Who Should Be Evaluated?
• Height < 3rd percentile (10% have pathology)*
• Height velocity < 2 inches (5 cm) per year
--Downward crossing of percentiles on growth chart after age 2-3 years of
age
• Height prediction below genetic potential or below the Target height.
• “Sick” children who do not grow as expected after initiation of therapy for their
“illness”
*Lacey KA, Parkin JM. Causes of short stature. A community study of children in Newcastle-uponTyne. Lancet 1974; 1:42-25.

8. Causes of Short Stature or Poor Growth
• Normal
oFamilial short stature
oConstitutional short stature
• “delayed growth and development”
• “late bloomers”

9. Familial Short Stature
• Family history of short stature
• Normal age of onset of puberty
• All lab tests are normal (ie. Healthy)
• Bone age is ~the same as the chronological age
• Predicted height and adult final height are consistent with
genetic potential or Target height

10. Familial Short Stature

11. Constitutional Growth Deley
• “slow growers” or “late bloomers”
• Family history of delayed puberty
• Normal growth velocity until 10-14 years of age for boys or 8-10 years for girls
• Delayed puberty: height deviates from growth curve at ~10-14 years
• Labs: wnl (i.e. healthy)
• Bone age delay: 2-4 years
• Later “catch-up growth”
• Normal height in adulthood: lower end of the normal height for their family (short for their
families)

12. Growth Velocity Curve--Boys
Early Puberty
Delayed
puberty

13. Constitutional
delay of growth
and development

14. Constitutional Delay of Growth:
Expected versus Final Adult Height
La Franchi S, Hanna CE, Mandel, SH Pediatrics,
1991; 87;82-87

15. To Grow Normally,
A child needs to be
….healthy
……..fed
………..and loved

16. Causes of Short Stature or Poor Growth
o Fed
• Nutritional*
• Low birth weight or length
(SGA=small for gestational age)
o Loved
• Psychosocial
o Healthy
• Endocrine
o Hypothyroidism
o Abnormalities of GH-IGF-1 axis
• Chromosome defects: Turner’s
Syndrome, Noonan’s Syndrome
• Bone development disorders
o SHOX deficiency
• Metabolic
• Chronic diseases and their
therapies
• Birth defects
Pathologic cause of short stature
We as providers need to confirm the child is…

17. Nutritional Growth Retardation (NGR)
• Real illness
o Inflammatory bowel disease
o Celiac disease
o Cystic fibrosis
o Cardiac, renal, HIV
• Poverty related malnutrition-worldwide
• Self-restricted nutrient intake in suburban upper middle class—
USA
o Patients have adapted to their suboptimal nutritional intake and may not
appear wasted

19. How Is SGA Defined?
Usher and McLean Growth Curves

20. Catch-up Growth in Children Born
SGA

21. Noonan Syndrome: What Physicians Need to Know
JA Noonan, MD, AE Roberts, MD, JDahlgren, PhD
Clinical Review, Medscape Pediatrics, September 2007

23. SHOX deficiency

24. Photo
Phenotype of GH receptor deficiency. Brothers, ages 3 7/12 (left) and 1 9/12 (right), were homozygous for nonsense mutations (R43X) in the GH receptor gene. Their
heights were -7.2 and -5 SD below mean for age, respectively.
A random blood sample obtained on the younger showed low levels of IGF-I (6 ng/ml; normal 17-248) and IGFBP-3
(0.2 mg/l; normal 0.9-4.1) in the face of moderately elevated circulating GH concentration (19.8 ng/ml). They were
treated with recombinant IGF-I for 11 years. During this time they grew 4.6 cm/yr on average, a growth velocity
slightly lower than that of normal children, but greater than that expected, in untreated patients with this diagnosis, [3]. Photographs and baseline laboratory data from
Rosenbloom et al. [42]. Used with permission.
Rosenbloom AL. J Pediatr Endocrinol Metab 1995;8:159-65.

26. Growth Hormone Deficiency
• Isolated
• Associated with multiple pituitary hormone deficiencies
o TSH, LH, FSH, ACTH, Vasopressin
• Congenital
o malformations/inherited genetic disorders
• Acquired
o tumors, head trauma, radiation therapy
Anything affecting CNS can result in GHD

27. The GH-IGF-IGFBPAxis
Transport
Cellular
IGFBP
Receptors
RXR-
Nuclear
actions
Nuclear
Receptors
Cell surface
BP-receptors
---IGFBPs
Type
IGF Receptor
I
a
b
Survival &
Mitogenesis
Via IRS-1 --
Akt, MAPK
and other
pathways
IGF-I
IGF-II
Insulin
GH
Differentiation,
growth, aging,
metabolism &
carcinogenesis
ALS
150 kDa complex
IGFBP-1 IGFBP-2 IGFBP-3 IGFBP-4 IGFBP-5 IGFBP-6
Type
IGF Receptor
II
IGF2 binding
Mannose-6-
phosphate binding
Retinoid binding
Growth
inhibition
GH
Cohen P. Horm Res 2006; 65 Suppl 1:p. 5.

28. Evaluation of Short Stature History
• Birth history
o Mother’s pregnancy
• Illness, toxins, alcohol/drugs,
• Peri-natal events
o Birth weight and length
• Medical history
o ROS (signs of chronic disease)
o Medication history
• Family history
o Height, “late bloomers” and pubertal timing
o Height of parents to calculate mid-parental height
o Significant “life” events (psychosocial)
• Growth curves

29. Physical Exam
• Height and weight
• Head circumference
• Body proportions (skeletal dysplasia?)
o Arm span
o Upper/segment ratio
• Dysmorphic features: metacarpals, midline craniofacial defects, Madelung
deformity, cubitus valgus
• Pubertal status
• Scoliosis
• Body proportions
• Signs of chronic illness: pallor, dry skin, poor dentition

30. Evaluation
• CBC
• ESR or C-Reactive Protein
• Biochemical profile
• T4, TSH. Anti-thyroglobulin and thyroid peroxidase antibodies
• Celiac Screen
• IGF-1/IGFBP-3
• Bone Age (for height prediction)
• Genetic tests: Karyotype (girls); SHOX and
• Skeletal survey if hypochondoplasia suspected (i.e.abnormal body
proportions)
• Growth Hormone testing
• MRI of the pituitary with and without gadolinium for children with growth
hormone deficiency

31. Psychosocial Consequences of Short Stature
• Overall : Most children have normal psychosocial function
• Short stature may be a risk factor for psychosocial problems*
o Social immaturity
o Infantilization
o Low self esteem
o Being bullied
*May be a function of several risk factors including parental attitudes and prevailing
cultural opinions
*Clinic-based populations may display greater psychosocial dysfunction
From Lawson Wilkins Consensus Statement on ISS JCEM epub Sept 2008

32. Short Stature: The Social Problem
Prejudice is pervasive
• “Feisty” refers to short people
• “Distinguished” used to describe a tall person
• “Look up to”; “look down upon”
• “how tall are you?” vs. “what is your height?”
• “Short People (Randy Newman)—”grubby little fingers, dirty little
minds, with no reason to live”
• Etc……..
“The Height of Your Life” by Ralph Keyes

33. "Children have a short time to grow and a lifetime to live with the results." ©
Major Aspects of Growth In Children
MAGIC FOUNDATION

34. Questions
Your Questions
Thank you…..