GROWTH DISORDERS

•	Causes of short stature.
•	Pathological conditions causing short stature.
•	Causes of tall stature.
•	Pathological conditions causing tall stature.

Definition of a short child:

Arbitrarily taken as any child whose height is below the 3rd percentile for the community.

Causes of short stature

Normal variant (80%)			Pathological (20%)
Familial short stature
Constitutional growth delay

Proportionate				Disproportionate
					Skeletal dysplasia
					Rickets

Prenatal		Postnatal	
IUGR			GIT
Chromosomal		Cardiopulmonary
Dysmorphism		Haematological
			Renal
			Endocrine
			Psycho-social

1.	Familial short stature

a.	Birth size is small.

b.	These children will be growing on the 3rd centile or below but parallel to the 3rd centile.

c.	The growth rate is usually normal.

d.	Family history of short stature.

e.	The adult height percentiles of both parents should be plotted on the child’s growth child to assess whether the child’s height is appropriate for the heights of the parents.

f.	Puberty occurs at normal age.

g.	Bone age is normal.

2.	Constitutional growth delay

a.	Normal birth size.

b.	Height velocity slows down till 1 year, when height < 3rd percentile, growth continues parallel to 3rd percentile.

c.	Often a family history of a parent being short as a child, with delayed puberty and eventual catch up to his peers.

d.	Puberty delayed.

e.	Bone age delayed and consistent with height age.

f.	Final adult height normal for genetics.

g.	Sexual development normal.

3.	Skeletal disorders

a.	Usually are familial, involving the intrinsic cartilage or bone defects, e.g. achondroplasia and the mucopolysaccharidoses.

b.	Features:

i.	reduced arm span / height ratio.

ii.	increased US:LS ratio.

iii.	weight gain is usually normal.

4.	Intrauterine growth retardation

a.	This results in growth retarded babies of appropriate gestational age. 

b.	Major causes: a variety of genetic disorders primarily affecting the fetus.

c.	An abnormal intrauterine environment due to maternal illness, placental insufficiency or intrauterine infection may also lead to poor fetal growth.

d.	If the insult to the fetus occurs early in gestation, cell number is reduced and the potential for catch up is diminished.

5.	Chronic disease

a.	Chronic disease involving any system is a major cause of growth failure, usually associated with a similar fall off in weight velocity.

b.	Chronic infections may also present as failure to grow and gain weight.

c.	A hormone or endocrine problem is unlikely to be the cause of poor growth if both the weight and height are affected.

d.	Nutritional insufficiency may contribute to the growth failure of chronic disease due to inadequate or inappropriate intake, poor absorption or impaired or excessive tissue utilization.

6.	Iatrogenic

a.	Corticosteroid excess seen in children with steroid treated chronic illnesses, such as severe asthma, juvenile arthritis and nephrotic syndrome.

b.	Irradiation to the head and spine may result in hypothalamic / pituitary dysfunction and poor spinal growth of the trunk with increased span height ratio and a reduced US:LS ratio.

7.	Chromosomal abnormalities and syndromes

a.	Turner syndrome and its variants is the most common chromosomal cause of short stature.

b.	This condition must be excluded in any girl with short stature as the typical phenotypic features may not be seen in the mosaic forms of Turner syndrome.

c.	The most common associated abnormality is ovarian dysgenesis resulting in failed pubertal development in 95% of cases.

d.	Other chromosomal disorders are: Noonan’s snydrome, Russell-Silver dwarfism and Aarskog syndrome.

8.	Psycho-social: due to neglect and lack of care.

Pathological causes of short stature

1.	Achondroplasia

a.	Genetics:

i.	transmitted as an autosomal dominant trait with complete penetrance.

ii.	Most cases result from a new mutation.

iii.	caused by mutations in the gene for fibroblast growth factor receptor-3 on chromosome 4.

b.	Clinical features:

System	Features	
General 	•	Short stature.
•	Disproportionately long trunk.	
Cranio-facial	•	Large head with brachycephaly.
•	Midfacial hypoplasia.
•	Narrow nasal passages.
•	Relative prognathism.
•	Frontal bossing.	
Musculo-skeletal	•	Genu varum.
•	Rhizomelic short limbs.
•	Brachydactyly.
•	Lumbar lordosis.
•	Trident appearance of the hand.
•	Average height of male: 131cm, female: 124cm.	
Complications	•	Hydrocephalus in 1 – 2%.
•	Sleep apnoea.
•	Spinal canal stenosis with neurological signs.
•	Slow motor development.
•	Mental development is normal.	

2.	Turner syndrome

a.	Genetics:

i.	caused by absence of one set of genes from the short arm of one X chromosome, 2/3 from the paternal set.

ii.	karyotype: 45, XO.

b.	Clinical features:

System	Features	
General 	•	Short stature.
•	Loose neck folds (cutis laxa) in infants.	
Cranio-facial	•	Webbed neck.
•	Low posterior hairline.
•	Ptosis, strabismus, amblyopia & cataracts.
•	Epicanthic folds.
•	Abnormal prominent ears.
•	Micrognathia.
•	High arch palate.	
Musculo-skeletal	•	Broad chest with wide-spaced nipples.
•	Cubitus valgus.
•	Madelung deformity.
•	Short 4th / 5th metacarpals.
•	Kyphoscoliosis.
•		
Gonads	•	No breast development by 12 years or not started menses by 14 years.
•	Ovarian dysgenesis with hypoplasia or absence of germinal elements.
•	Pubic hair development is normal.	
CNS	•	Mild development delay.
•	Hearing impairment.	
CVS	•	Bicuspid aortic valve (30%).
•	Coarctation of aorta (10%).
•	Aortic steonsis.
•	Mitral valve prolapse.
•	Hypertension.	
Renal	•	Horseshoe kidney.
•	Double renal pelvis.	
Nail	•	Narrow hyperconvex nail	
Skin	•	Multiple pigmented naevi.	
Lymph vessels	•	Congenital lymphoedema (puffy fingers and toes).	
Complications	•	GI bleeding.
•	Increased incidence of inflammatory bowel disease.
•	Congenital hip dislocation.
•	Thyroid: positive antithyroid antibodies leading to hypothyroidism.	

3.	Noonan syndrome:

a.	Genetics:

i.	Autosomal dominant condition.

ii.	Usually sporadic.

System	Features	
General 	•	Short stature.	
Cranio-facial	•	Triangle shaped face.
•	Hypertelorism.
•	Down-slanting eyes.
•	Ptosis, strabismus, amblyopia.
•	Low-set ears with thickened helices.
•	High nasal bridge.
•	Short webbed neck.
•	Low posterior hairline.	
Musculo-skeletal	•	Shield chest.
•	Pectus excavatum.
•	Pectus carinatum.
•	Cubitus valgus.
•	Scoliosis.	
CVS	•	Pulmonary valve stennosis.
•	PDA, VSD, ASD.
•	Hypertrophic cardiomyopathy.	
Skin	•	Lymphoedema.
•	Prominent pads on fingers and toes.	
CNS	•	Mild mental retardation.
•	Hypotonia.
•	Seizures.	
Complications	•	Bleeding diathesis.	

Causes of tall stature

Normal					Pathological
Constitutional				
Pre-adolescent obesity

		Endocrine		Syndromic
		GH excess		Marfan’s
		Precocious puberty	Homocystinuria
		Thyrotoxicosis		Klinefelter’s

Pathological causes of tall stature

1.	Marfan’s syndrome

a.	Genetics:

i.	Marfan syndrome is an inherited connective tissue disorder transmitted as an autosomal dominant trait.

ii.	the disorder results from molecular defects in the fibrillin gene located on chromosome 15q21.1.

iii.	the gene encodes the glycoprotein fibrillin, a major building block of glycofibrils, which constitute the structural components of the sensory ligaments of the lens and serve as substrates for elastin in the aorta and other connective tissues.

b.	Clinical features:

System	Features	
General 	•	Tall stature.	
Cranio-facial	•	Malar hypoplasia.
•	Enophthalmos.
•	Retrognathia.
•	Down-slanting palpebral fissures.
•	High arched palate.
•	Dental crowding.	
Musculo-skeletal	•	Muscle hypotonia.
•	Joint laxity.
•	Decreased US:LS ratio.
•	Increased arm-span to height ratio > 1.05.
•	Pectus excavatum or carinatum.
•	Pes planus: medial displacement of medial malleolus.
•	Kyphoscoliosis.
•	Arachnodactyly.	
Eyes	•	Upward lens subluxation.
•	Myopia.
•	Retinal detachment.
•	Cataracts.
•	Glaucoma.	
CVS	•	Aortic root dilatation.
•	Dissecting aortic aneurysm.
•	Mitral valve prolapse.	
Pulmonary	•	Spontaneous pneumothorax.	
Skin	•	Striae atrophicae.
•	Recurrent or incisional hernia.	

2.	Homocystinuria

a.	Genetics:

i.	prevalence 1:200 000.

ii.	autosomal recessive.

iii.	enzyme deficiency: cystathionine synthase.

iv.	biochemical result: homocysteine and methionine accumulation.

b.	Clinical features:

System	Features	
General 	•	Tall stature.
•	Marfanoid habitus.
•	Fair skin and hair.	
Cranio-facial	•	Malar flush.
•	Blue eyes.
•	Downwards lens subluxation.	
CVS	•	Arterial and venous thromboembolism.	
CNS	•	Mental retardation.
•	Seizures.	
Skeletal	•	Osteoporosis.	

3.	Klinefelter’s syndrome

a.	Genetics:

i.	prevalence 1: 500 males.

ii.	most common chromosomal disorder associated with male hypogonadism and infertility.

iii.	defined by a 47, XXY karyotype with additional X and Y chromosomes.

b.	Clinical features:

System	Features	
General 	•	Features are very variable.	
Musculo-skeletal	•	Low US:LS ratio.
•	Long arms and legs.	
CNS	•	Mild mental retardation.	
CVS	•	Mitral valve prolapse.
•	Varicose veins.	
Genitalia	•	Small penis & testes in childhood, most enter puberty normally.
•	Primary infertility.
•	Partial virilization.
•	Gynaecomastia.
•	Lack of secondary sex characteristics.