SHORT STATURE

All of the above

[Noonan syndrome]

Noonan syndrome – Autosomal dominant gene with variable expressivity, the gene has mapped to chromosome 12q. Most common abnormalities are – short stature, webbing of neck, pectus carinatum or pectus excavatum, cubitus valgus, right sided congenital heart disease

• ·Hypertelorism, epicanthus, downward slanted palpebral fissure, ptosis, micrognathia and ear abnormality
• ·Clinodactyly, moderate mental retardation, high frequency sensorineural hearing loss is common
• ·The cardiac defect Q is most often pulmonary valvular stenosis, hypertrophic cardiomyopathy or ASD
• ·Low clotting factors XI or XII, ALL and CML have been described
• ·A few patient with neurofibromatosis I and features of Noonan syndrome were subsequently reported as
  havinq Turner syndrome, Male frequently have Cryptorchidism and small testes, they may be hypogonadal or
  normal.

Physiological short stature resulting from normal variants of growth is more common than pathological short stature. Amongst the options provided constitutional delay is the only example of physiological short stature and is hence the single option of choice.

Ref: O P Ghai 6th Edition, Page 50

• Height more than 3.5 SD below the mean for chronologic age;
• Growth rate more than 2 SD below the mean for chronologic age; and
• Height more than 2 SD below the target height when corrected for midparental height.

The patient is showing features of neurologic cretinism characterized by deaf-mutism, mental retardation, squint, proximal spasticity, and rigidity more in the lower extremities, disorders of gait and stance and occasional signs of cerebellar or oculomotor disturbance. Neurologic cretinism is a type of endemic cretinism caused by decreased intake of iodine (less than 25microg/d) in contrast to a normal intake of 80-150microg/d.

Ans. is ‘d’ i.e., 45 X

TURNER’S SYNDROME

o Turner’s syndrome is the most common sex chromosomal disorder in phenotypic females.

o Turner’s syndrome results from complete or partial loss of one X chromosome (45, X) and is characterised by hypogonadism in phenotypic females

Features of Turner syndrome in children

o The most severely affected patients generally present during infancy with edema (owing to lymph stasis) of the dorsum of the hand and foot and sometimes swelling of the nape of the neck.

• Swelling of the neck is related to markedly distended lymphatic channels, producing so called cystic hygroma. o As these infants develop, the swelling subsides but often leave bilateral neck webbing and persistent looseness of skin on the back of the neck.

o Congenital heart disease is also common, particularly preductal coarctation ofAorta and bicuspid Aortic valve.

• C. VS abnormalities are most important cause of mortality in children with Turner’s syndrome. Features of Turner’s syndrome in Adolescents and Adult

o At puberty there is failure to develop normal secondary sex characteristics.

o The genitalia remains infantile, breast development is inadequate and there is little pubic hair. Nipples are widely spaced.

o Turner syndrome is the single most important cause of primary amenorrhoea accounting for approximately  ¹/3 of the cases.

o Short stature (height rarely exceeds 150 cm).

o The mental status of these patients is usually normal but subtle defects in nonverbal, visual spatial information processing have been noted (mental retardation is associated with the presence of extra chromosome not with loss of X chromosome).

o About 50% of the patients develop autoantibodies directed to the thyroid gland and upto one half of these patients develop hypothyroidism.

o Other features include low posterior hairline, webbing of neck, cubitus valgus, streak ovaries. o Glucose intolerance, obesity and insulin resistance are also seen.

Ans. is ‘a’ i.e., Maternal deprivation syndrome; ‘b’ i.e., Hypothyroidism

o If the height of the child is below the 3rd percentile or less than 2 S.D. from the mean, he or she is considered to be short stature.

o Causes of short stature

A) Proportionate short stature

Normal variant          –              

1) Familial

2) Constitutional delay in growth

Prenatal causes                         

1) Intrauterine growth retardation (IUGR)

2)    Intrauterine infections

3)    Genetic disroders (chromosomal and metabolic)

Posnatal causes         –              

1) Nutritional dwarfism (due to malnutrition)

2)    Chronic visceral disease

3)    Endocrine disorders (hypopituitrism, Juvenile DM)

4)   Psychosocial (emotional deprivation, maternal deprivation)

B) Disproportionate short stature

• With short limbs – Achondroplasia, hypochondroplasia, chondroectodermal dysplasia, deformities due to rickets and osteogenesis imperfecta, hypothyroidism.
• With short trunk : Spondylo-epiphyseal dysplasia, mucoplysaccharidosis, mucolipidosis, caries spine, hemivertebrae.

Ans. is ‘a’ i.e., Normal body proportion

Short stature due to Human Growth hormone deficiency in characterized by ‑

1. Ratio of upper to lower segment is normal.

2. Bone age or epiphyseal development in less than chronological age by about 2 years.

3. Children’s are normal in height and weight at birth.

4. Delay in growth is usually observed after the age of one year.

Bone age in less than the chronological age in –

o Constitution delay in puberty.

o Marked delayed in hypothyroidism and hypopituitarism.

o Moderate delay in malnutrition and chronic illnesses.

Bone age is advance than height age in

o Down’s syndromes Intrauterine infections            

o Turners syndrome

Ans. is ‘b’ i.e., Juvenile Nephronophthisis

The lab investigations and symptoms of the child suggest Juvenile nephronophthisis.

Juvenile nephronophthisis

o It is the most common genetic cause of end stage renal disease (renal failure) in childhood and adolescence.

o It is an autosomal recessive disease.

o The patients present before the age of 20 years.

o The pt. presents with

        Inability to conserve sodium because of defect of tubules leading to polyurea and polydypsia (Polyurea is resistant to vasopressin)

        Anemia

        Growth retardation (growth retardation, malaise & pallor are secondary to anemia which is attributed to a def. of erythropoietin production by failing kidneys)

        No hypertension (As nephronopthosis is a salt-losing nephropathy)

        Proteinuria and hematuria usually are absent

        Sonography shows b/1 small kidneys with multiple cysts only in medulla (cysts may only be seen if they are large enough. They are rarely visible early in disease)

o Juvenile nephronopthosis is usually associated with many extra renal conditions, one of which is hepatic fibrosis, which explains high level of alkaline phosphatase in this patient.

o Radiographic features

• Small kidneys      
• Loss of cortico medullary junction         
• Multiple cysts

About other options

Medullary cystic disease

o Patient with medullary cystic disease presents with similar features as Juvenile Nephronophthisis but it can be differentiated by –

o Absence of Growth Retardation

        Age of presentation is 3rd or 4th Decade.

        Hypertension may occur (in JN, hypertension is not seen).

In polycystic kidney disease there is bilateral enlargement of kidney.

In reflux Nephropathy the kidneys does not decrease in size and there will be history of frequent urinary tract infections.

Ans. is ‘d’ i.e., Nephronopthisis

o Features seen in this 13 yr. old boy

       Short stature                                                               Hyponatremia (N level in 136-145 meq/dl)

       Nocturnal enuresis                                                       Hypocalcemia (N level is 9-10.5 mg/dl)

       Normal B.P.                                                                Normal potassium level (N is 3.5 to 5 meq/dl)

       Reduced haemoglobin                                                 B/L small kidneys

      Increased blood urea (N is 10 — 40 mg/dl)                     Increased alkaline phosphatase (N is upto 1301U)

      Increased serum creatinine (N is < 1.5 m g/dl)

o This pt. gives classical presentation of nephronopthosis, (See above explanation)

About other options

Alports syndrome

• It can be easily ruled out as it presents with

         Microscopic hematuria (first symptom)                         Sensorineural hearing loss

         Proteinuria                                                               b/1 anterior lenticonus

Medullary sponge kidney

Easily ruled out as the kidneys are normal or increased is size in MSK and also the age of presentation is third or fourth decade.

Chronic glomerulonephritis

pts of CGN usually have heavy proteinuria, frank or occult hematuria and hypertension.

. Ans. is ‘a’ i.e., Short limbs compared to trunk; ‘c’ i.e., Short limbs and short stature

“The child’s growth is stunted and the extremeties are short. The hands are broad and the fingers are short”. “The child appears short and stocky”.

Ans is ‘a’ i.e., Thyroid Dyshormonogenesis

o This child has :‑

i)           Thyroid swelling

ii)          Low T₄ & High TSH

iii)        Abnormal weight gain and poor activities

o All these suggests the diagnosis of congenital hypothyroidism due to thyroid disorder (In hypothalamic diseases, TSH levels will be low).

o The most common cause of non – endemic congenital hypothyroidism is thyroid dysgenesis.

i)      In endemic regions Most common cause of congenital hypothyroidism is iodine deficiency in intrauterine and neonatal period (world wide).

ii)     In non-endemic regions Most common cause of congenital hypothyroidism is thyroid dysgenesis.

o However, in thyroid dysgenesis, thyroid gland does not enlarge to produce palpable goitre. So, this option is ex­cluded.

o Dyshormogensis is an uncommon cause of congenital goitrous hypothyroidism and account only about 10-15% of cases of congenital hypothyroidism. It results from a deficiency of one or more enzymes (most commonly, thyroid peroxidase) involved in thyroid hormone synthesis or secretion.

o So, amongst the given options, best answer is Dyshormogenesis.

o You keep in mind that the most common cause of congenital hypothyroidism with similar presentation (palpable goitre) is iodine deficiency.

Ans. is ‘b’ i.e., Growth hormone deficiency

Clinical features of Growth hormone deficiency

o Short children with normal body proportions

o Markely increased subcutaneous fat

o Delayed skeletal age than chronological age

o The height age is less than skeletal age and chronological age.

o Hypoplastic penis and scrotum

o May present with severe hypoglycemic convulsions.

o Crowding of midfacial features

o Genitals are small (sexual infantilism)

o Truncal obesity.

o High pitched voice

o Depressed nasal bridge o Prominent philtrum

o Frontal bossing

o Delayed sexual maturation o Delayed tooth eruption

Ans. is ‘a’ i.e., Elderly primi; ‘b’ i.e., Short stature primi 

Risk approach

o The central purpose of antenatal care is to identify “high risk” cases and arrange skilled care for them, while continuing to provide appropriate care for all mothers.

o These high risk cases are ‑

1. Elderly primi (30 years and over)
2. Short statured primi (140 cm and below)
3. Malpresentations, viz breech, transverse lie, etc
4. Antepartum haemorrhage, threatened abortion
5. Pre-eclampsia and eclampsia
6. Anaemia
7. Twins, hydramnios
8. Previous still-birth, intrauterine death, manual removal of placenta
9. Elderly grandmultiparas
10. Prolonged pregnancy (14 days-after expected date of delivery)
11. History of previous caesarean or instrumental delivery
12. Pregnancy associated with general diaseases, viz. Cardiovascular disease, kidney disease, diabetes, tuberculosis, liver disease, etc.

Answer is C (Unilateral renal dysplasia):

The multicystic dysplastic kidney is the commonest form of congenital cystic renal dysplasia, and is due to complete uretric obstruction in fetal life. The condition is usually unilateral; bilateral disease is lethal.

Cystic diseases of kidney in infants

• Dysplastic kidney (multicystic)
• Polycystic kidney (Autosomal Recessive; Autosomal dominant)
• Multilocular cystic nephroma

Renal dvsplasia. Multicvstic kidney:

‘It is the commonest cause of renal mass in infants’

Ans. B: Familial short stature

Delayed bone age in a child with short stature is suggestive of hormonal/systemic disorder.

Normal bone age in a short patient is more likely to be caused by a genetic cartilage dysplasia or growth plate disorder.

The hallmarks of familial short stature (also referred to as genetic short stature) include bone age appropriate for chronologic age, normal growth velocity, and predicted adult height appropriate to the familial pattern (using the Bayley­Pinneau or Tanner-Goldstein-Whitehouse tables). By contrast, constitutional growth delay is characterized by delayed bone age, normal growth velocity, and predicted adult height appropriate to the familial pattern

Ans. A: Constitutional

The causes of short stature can be divided into 3 broad categories:

• Chronic disease (including undernutrition genetic disorders)
• Familial short stature
• Constitutional delay of growth and development (commoner)

Endocrine diseases are rare causes of short stature.

The hallmark of endocrine disease is linear growth failure that occurs to a greater degree than weight loss.

Ans. Turner syndrome

Ans. Mental retardation

The disorder shown in the picture above represents Turner syndrome.

Maternal age constitutes an important influence on the incidence of Down’s syndrome. Occurance of Turner’s syndrome is not affected by maternal age.

• Turner’s syndrome is the most common cause of primary amenorrhea. At puberty sexual maturation fails to occur and primary amenorrhea is common.
• Short stature is characteristic of Turner’s syndrome.
• Lymphoedema of the dorsum of hands and feet is also a characteristic finding in patients with Turner’s syndrome.