This document summarizes key information about three pediatric genetic syndromes: Down syndrome, Klinefelter syndrome, and Turner syndrome. It describes the genetic causes and characteristics of each syndrome, including physical features, associated medical conditions, diagnosis, recurrence risks, and management approaches. Down syndrome is caused by trisomy 21 and is characterized by developmental delay, distinctive facial features, and occasionally congenital heart defects. Klinefelter syndrome affects males and is caused by an extra X chromosome, with symptoms including delayed puberty, gynecomastia, and infertility. Turner syndrome occurs in females missing an X chromosome and involves short stature, neck and heart issues, and sexual infantilism.

1. 15. Pediatric Lecture Notes on Pediatric Genetics1
15.1 Down Syndrome. (Trisomy 21)
15.2 Klinefelter Syndrome.
15.3 Turner Syndrome.
15.1. Down Syndrome.
15.1.1. Introduction.
1. Most commen autosomal chromosomal abnormality. Chromosome
No. 21 is present in triplicate.
2. Incidence: 1:700 live births (50% of cases abort in early pregnancy.)
Incidence increases with increasing maternal age.
S. no. Age of mother Risk
1 20 Years. 1:2000
2 30 Years 1:1000
3 40 Years 1:100
3. Cytogenetics – 92% cases have trisomy with extra chromosome no 21
with all body cells. Total chromosome 47.
a) Non disjunction During maternal meiosis is most commen 80-
90%.
b) Translocation (5%) of 21 chromosomes to another chromosome
usually of D group (13,14,15) or G group (21,22) chromosome.
Total chromosome 46.
c) Mosaicism – 0.3% Some cells have trisomy 21 other cells normal.
15.1.2. Clinically:
a. Newborn:
I. Poor Moro’s reflex - (85%)
II. Joint hyperflexibility (85%).
III. Excessive skin at back of neck
IV. Flat facies.
V. Developmental delay.
VI. Small stature.
b. Children:
A. Hypotonia – 81%.
B. Mental retardation.
C. Short stature
D. 40% CHD Endocardial cushion defect (VSD).
E. Facial features:
a. Brachycephaly (small)

2. b. Small mid face.
c. Up tuned nose.
d. Flat occiput.
e. Tongue protruded due to small mandible and maxilla furrowed
tongue.
f. Delayed closure of fontanel.
g. High narrow palate.
F. Eye Changes:
a. Epicanthic fold.
b. Brush field spots on iris.
c. Up slanting palpable fissures.
d. Cataract.
e. Squint.
f. Vision – myopia.
G. Bowel Abnormalities:
a. TEF.
b. Oeusophageal and duodenal atresia.
c. Annular pancreas.
d. Duodenal web.
e. Hirschsprung’s Disease.
H. Hands:
a. Short broad.
b. Single palmer crease (Simian crease).
c. Clinodactyly.
d. Sydney line parallel to simian crease.
I. Feet’s:
a. Kennedy crease: A crease between the Great and second
toes of both feet.
b. Increased space between 1st
and 2nd
toe.
J. Skin:
a. Velvety.
b. Loose.
c. Mottled in Newborn.
d. During adolescence skin is coarse and dry.
K. Social aspects: Happy children friendly and enjoy music.
L. Increased risk for:
a. Leukemia.
b. Hypothyroid.
c. Alzheimer’s disease (Problem in 3rd
and 4th
decade –
dementia)
d. Respiratory infection.
M. Dermatoglyphics:
a. Distal Axial Triradius.

3. b. Ulnar loops in 1st
three fingers, radial loops in two
fingers.
c. Large ATD angle.
15.1.3. Screening for Down Syndrome in next pregnancy Antenatally.
A. > 35 Years – Maternal chorionic villi biopsy – cytogenetics.
B. Age < 35 Years
a. Triple test.
i. Maternal serum α fetoprotein decreased.
ii. Maternal unconjugated estriol decreased.
iii. Gonadotropins increased.
b. USG. Suggestion of Down syndrome.
i. Thick nuchal fold.
ii. Short femur.
iii. CHD.
iv. GIT anomaly.
v. Clinodactyly.
15.1.4. Recurrence risk:
1. Translocation: Subsequent chance of 5to100%.
2. 21/21 translocation 100%.
3. Non disjunction 1% risk.
4. Mosaicism.
15.1.5. Management:
1. Genetic counselling.
2. Antenatal diagnosis for subsequent pregnancies.
3. Stimulation programme.
4. Assessment of Growth, vision, hearing and behavior.
15.2. Klinefelter Syndrome.
A. Most commen sex chromosome aneuploidy.
B. Karyotype 47 XXY.
C. Incidence:
i. Sporadic.
ii. Increases maternal age predisposes.
iii. Chromosomal aberration results from meiotic non disjunction of X
chromosome during parenteral gametogenesis.
D. Clinical features:
1) Genitalia – Masculine.
2) Male phenotype.
3) No clinical manifestation during childhood. Diagnosis at puberty.
4) Diagnosis considered in all boys with mental retardation and in children
with psychosocial learning or school adjustment problems.
5) Child may be anxious, excessively shy or aggressive. May engage in
antisocial acts.

4. 6) Fire setting behavior may be observed.
7) Delay in language acquisition.
8) Physique – Tall slim underweight with relatively long legs.
9) Genitalia
a) Testes small for age.
b) Phallus smaller.
c) Cryptorchidism.
d) Hypospadias may occur
E. Pubertal development delayed.
F. Gynecomastia in 80%.
G. Sparse facial hair.
H. Azoospermia and infertility.
I. More prone to develop (15 to 30%)
a) Pulmonary diseases.
b) Mediastinal germ cell tumor.
c) Breast cancer.
d) Leukemia.
e) Lymphoma.
f) Other hematological neoplasia.
J. Diagnosis:
• Testosterone level becomes low.
• Karyotype Barr bodies positive.
K. Treatment:
Replacement therapy with long acting testosterone.
Testosterone therapy:
 Testosterone enanthate.
 Begin at 11 to 12 yrs of age.
 Dose: Start from 25 – 50 mg/IM every 3to4 weeks, increase dose every
6to9 months by 50mg till the maintenance dose of 200 to 250 is reached.
15.3. Turner Syndrome.
15.3.1. Definition: Combination of characteristic phenotypic features along with
access of second X chromosome with or without mosaicism.
Karyotype – 45X0
Genitalia – female.
Inheritance – mosaic with isochromosomes.
15.3.2. Clinical features:
A. At Birth.
o Edema to hands and feet.
o Loose skin fold at nape of neck.
o LBW.
o Decreased length
B. Childhood.

5. o Short stature.
o Webbing of neck.
o Low posterior hairline.
o Small mandible.
o Prominent ears.
o Epicanthic folds in eye.
o High arched palate.
o Broad chest.
o Hyper convex finger nail.
o Cubitus valgus.
o Sexual infantilism.
o Associated abnormalities:
1. Bicuspid Aortic valve, Coarctation of aorta.
2. Renal abnormalities.
3. Autoimmune thyroiditis.
4. Inflammatory bowel disease.
o Hormone profile: Decreased plasma estradiol, increased FSH
and increased LH.
15.3.3. Diagnosis:
1. Hormone profile.
2. Karyotype, Barr bodies absent.
15.3.4. Treatment:
1. Recombinant Growth hormone.
2. Replacement therapy with estrogen – Premarin 0.3mg OD × 6months.
3. Treatment of associated abnormalities.
4. Psychosocial support.
1. Parthasarathy, K Nedunchalian, Gowri Shankar HC, Textbook of Balram chowdhary’s Pediatrics
Lecture notes, PEE PEE Publication, 2nd edition, Pg no. 340 – 343.