Down Syndrome (Trisomy 21)

Cytogenics

Miotic non disjunction (94%) Translocation/ Robertsonian Mosaicism (1%)

translocation (5%)
 error at meiosis – pair of  extra chromosome joint into  some cell are normal, some have
chromosome 21 fail to separate – another chromosome (C14, 15, 22, trisomy 21. d/t formation of
one gamete has 2 chromosome and 21) chromosomally normal zygote by
one has one – fertilization of gamete non disjunction mitosis
w 2 chromosome 21 give rise to
zygote w trisomy 21 – every cell
have extra 21 chromosomes
- Risk for recurrence in next
pregnancy: 1/200

Accompany w:

 Congenital heart disease (30%) – AV canal defect, VSD, ASD, valvular disease
 Duodenal atresia, annular pancreas, imperforated anus
 Hirschprung disease – absence of ganglion cell in bowel – loss of peristalsis – intestinal obstruction, constipation, growth failure,
unexplained fever, vomiting
 Polycythemia (Hct>70%) – self limiting

C/F

 Hypotonic
 Single palmar crease, incurved 5th finger, wide
sandal gap btw big & second toe
 Craniofacial: round face, flat nasal bridge,
upslanted palpebral fissure, epicanthic folds
(upper eyelid skin fold cover inner corner of eye),
brushfield spot in iris (small, white spot arranged
in ring), small mouth, protruding tongue, low set
& small ear, flat occiput, brachycephaly/ shape of
skull shorter
 Short neck

Complication: Ix:
 Hypothyroidism, coeliac disease  FISH (fluorescent in situ hybridisation)
 Epilepsy  Amniocentesis- check fetal karyotype
 Impairment of vision (cataracts, squints, myopia)  Chromosome analysis
 Impairment of hearing (secretory otitis media)
 Atlanto-axial instability – increase distance between C1, C2 (cervical rotation)
– predispose to spinal injury
 Delayed motor milestones, Learning difficulties
 Increase susceptibility to infections
 Alzheimer disease (>35 y/o), AML, acute lymphoblastic leukemia
Edwards Syndrome/ Trisomy 18 (47, XX+18/ 47 XY+18) – 2nd most common

 <10% affected infant survive until 1st birthday

 C/F: hypertonia, prominent occiput, micrognathia/ small jaw, low set ear, rocker bottom feet (prominent calcaneus, convex
rounded bottom of foot) , hypoplastic nail, flexed & overlapping fingers, short sternum
 Investigations: chromosome analysis, ultrasound scan during 2nd trimester, amniocentesis

Patau Syndrome/ Trisomy 13 (47XX +13/ 47XY +13)

 Fatal in 1st year of life

 C/F: structural defect of brain, scalp defects, small eye/ microphthalmia, cleft lip & palate, polydactyly, carial & renal
malformations

Klinefelter Syndrome (47 XXY)

 Presence of extra X chromosome (non disjunction, from sperm/ egg)

 Diagnosis made when 15/16 y/o
 C/F: development of pubic & axillary hair in the presence of testes remain infantile in volume, tall stature w long limbs,
gynaecomastia, hypogonadism, small testes, failure to growth & maturation of testes – deficiency in testosterone – failure to
produce viable sperm – fail to develop secondary sexual characteristics (facial hair, deepening of hair, libido), osteoporosis,
osteopenia in adult, normal intellectual, educational & psychological problems

Turner Syndrome (45X)

 C/F: low set ear, triangular face, flattened nasal bridge, epicanthal folds (upper eyelid covering the inner fold), puffiness of hand
& feet, spoon-shaped nails, lymphoedema of hands & feet in neonate, short stature, wide spaced nipples
 Malformation: COA (45%), bicuspid aortic valve, post stenotic aortic dilation w aneurysm, horseshoe shaped kidney, acquired
hypothyroidism, gonadal dysgenesis – estrogen deficiency – fail to develop secondary sexual characteristics -- amenorrhea

Mendelian Inheritance

Autosomal Dominant Inheritance

 Alter in only one copy of gene pair

 Autosomal dominant gene on chromosome 1-22, male & female are equally affected
 Ex: achondroplasia, Ehler-Danlos syndrome, Familial hypercholesterolemia, Huntington disease, neurofibromatosis, tuberculos
sclerosis

Autosomal Recessive Inheritance

 Affected individual- homozygous for abnormal gene, having inherited abnormal allele from each parent
 Parents – unaffected heterozygous carrier, risk of each child being affected is 1 in 4 (25%)

Consanguinity

Nelson 122