Dysmorphic Child

Question 1

Karyotyping

Answer 1

It is photographing of chromosomes to show its number
and any abnormalities. • It is the chromosomal configuration of an individual and
was found to be as an individual finger prints. • The chromosomes are arranged in pairs in order of
length and the position of the centromere • The pairs are numbered from 1 to 22 leaving a pair of
extra chromosomes (XX in females and XY in males). • A normal karyotype is recorded as (46XX) or (46XY). • The genetic make up of an individual is called genotype,
while the resulting effect produced is the phenotype.

Question 2

The importance of chromosomal studies

Answer 2

1- it helps clinical diagnosis in patients with mental subnormalities or congenital malformations.
3- chromosomal study is essential as it may be the cause in repeated spontaneous 1 st trimester abortion , infertility or primary amenorrhea.
2- In malignancy: Lymphoma —————————- ch. 14 abnormalities. Retinoblastoma————————ch 13 deletion. Chronic myelogenous leukemia—-Philadelphia ch.
Indications of chromosomal studies
4- Prenatal diagnosis by karyotyping the fetal cells (by amniocentesis), is essential in familial chromosomal abnormalities.
5- Study of the relationship among species by knowing the similarities among their chromosomes.

Question 3

Genetic counseling

Answer 3

Definition: It is the procedure which deals with genetic problems.

indications: 1-The birth of a child with MR or congenital anomalies, for prognosis and recurrence risk. 2-Carrier detection. 3-Consanguinous marriage. 4-Recurrence risk for genetically determined disease. 5-Affected parent with hereditary disease may seek genetic advice. 6- Disputed paternity. 7- Rh incompatibility

Question 4

Euploidy

Triploid

Tetraploid

Answer 4

Euploidy: (Ploidy refers to the number of chromosomal sets.) The basic haploid number in man is 23 (n). Normally we have dipliod number which is 46 (2n). Euploid refers to the karyotype which has any multiple of the basic haploid.
Triploid may result from failure of one of the maturation division of the ovum or the sperm. (1n+2n=3n).
Tetraploid may result from failure of the first cleavage
division of the zygot. ( 2n+2n=4n ).

Question 5

2-Aneuploidy

Answer 5

It is the deploid number with an extra or missing chromosome e.g. Trisomy: (46+1) Down syndrome, trisomy 21 Monosomy: (46-1) turner syndrome.
Aneuploidy is caused by nondisjunction which is failure of one of the sister chromosome to disjoin.

Question 6

Structural aberrations

1- Translocation:(Balanced or unbalanced)

Answer 6

1- Translocation:(Balanced or unbalanced) -Chromosomal translocation is a phenomenon that results in unusual REarrangement of the chromosomes. -It is transfer of material from one chromosome to a non homologous chromosome. -Unbalanced translocation: The exchange of chromosomal material is unequal resulting in extra or missing genes. Translocation carrier: (Balanced translocation) Is a phenotypically free individual as his genetic material is practically unaltered. However this translocation interferes with normal separation the chromosomes during meiosis.

Question 7

Crossing Over

Answer 7

Is a physiological process that occurs during cell division between homologous pair of chromosomes at the area of chiasmata where segments from chromatids of one chromosome exchange places with corresponding segments of the other homologous chromosome It prevents accumulation of genes in the family and produce new combination

Question 8

Structural

Answer 8

4- Inversion: is fragmentation of a chromosome followed by reconstitution in an inverted way.

Question 9

• Mosaicism

Answer 9

A chromosomal mosaic patient is an individual who has at least
two cell lines with different karyotypes.

Question 10

Turner syndrome

Genotypes:

Answer 10

1-Monosomy X. (45 XO) 60% The missing chromosome is usually the paternal.
2- Mosaicism: (XO/XX) 15%.
3-Structural aberrations: Deletion of the short arm or deletion of the long arm or ring chromosome.

Question 11

Clinical Features Of Turner Syndrome

Answer 11

Clinical Features Of Turner Syndrome
1-Female with prominent auricles and low posterior hair lines. 2-Short stature. 3-Broad chest with widly separatted nipples. 4-Mental subnormality. 5-Primary amenorrhoea and ovarian dysgenesis. 6- Absent sex characters. 7-Webbing of the neck. 8-Congenital lymphoedema. 9- Renal anomalies. 10-Cardiac anomalies (coarctation). 11-Abnormal brown spots (navi). 12- Cubitus valgus.

Question 12

’ Clinical Features Of Turner Syndrome

Answer 12

Clinical Features Of Turner Syndrome
1-Female with prominent auricles and low posterior hair lines. 2-Short stature. 3-Broad chest with widly separatted nipples. 4-Mental subnormality. 5-Primary amenorrhoea and ovarian dysgenesis. 6- Absent sex characters. 7-Webbing of the neck. 8-Congenital lymphoedema. 9- Renal anomalies. 10-Cardiac anomalies (coarctation). 11-Abnormal brown spots (navi). 12- Cubitus valgus.

Question 13

’ Clinical Features Of Turner Syndrome

Answer 13

Clinical Features Of Turner Syndrome
1-Female with prominent auricles and low posterior hair lines. 2-Short stature. 3-Broad chest with widly separatted nipples. 4-Mental subnormality. 5-Primary amenorrhoea and ovarian dysgenesis. 6- Absent sex characters. 7-Webbing of the neck. 8-Congenital lymphoedema. 9- Renal anomalies. 10-Cardiac anomalies (coarctation). 11-Abnormal brown spots (navi). 12- Cubitus valgus.

Question 14

’ Clinical Features Of Turner Syndrome

Answer 14

Clinical Features Of Turner Syndrome
1-Female with prominent auricles and low posterior hair lines. 2-Short stature. 3-Broad chest with widly separatted nipples. 4-Mental subnormality. 5-Primary amenorrhoea and ovarian dysgenesis. 6- Absent sex characters. 7-Webbing of the neck. 8-Congenital lymphoedema. 9- Renal anomalies. 10-Cardiac anomalies (coarctation). 11-Abnormal brown spots (navi). 12- Cubitus valgus.

Question 15

2-Klinefelter Syndrome

Genotypes:

Answer 15

1- XXY (commonest 60%) due to maternal non disjunction. 2- XY/XXY mosaic (15%).

Question 16

2-Klinefelter Syndrome

Cp

Answer 16

Clinical Features: 1-abnormally long legs, the arm span is greater than height. 2- Hypogonadism (small testes and penis) and infertility . 3-Absent facial, axillary, pubic, or body hair. 4- A feminine distribution of adipose tissue, including Gynecomastia

Question 17

Complications of Klinefelter Syndrome: مهم ‘

Answer 17

Complications of Klinefelter Syndrome: 1-Breast carcinoma 20 times more in patients with KS.
2-Autoimmune Disorders as SLE, rheumatoid arthritis.
3-Intellectual and Psychiatric Disorders leads to poor school performance and delayed speech and language acquisition.
4-Osteoporosis.
5-Diabetes mellitus.

Question 18

3-Marfan Syndrome

Answer 18

s an autosomal dominant trait due to gene mutations on ch.15 which is essential for the integrity of CT.
- The signs and symptoms of Marfan syndrome vary greatly, even among members of the same family.
-Some experience only mild effects, but others develop life-threatening complications.
- In most cases, the disease tends to worsen with age.
Marfan syndrome features 1-Disproporte long limbs, fingers and toes. 2-Scoliosis, thoracic lordosis, pectus excavatum or pectus carinatum. 3-Abnormal joint flexibility. 4-A high-arched palate,crowded teeth. 5- Speech disorders due to high palates and small jaws. 6-Extreme nearsightedness. 7-Flat feet, hammer toes. 8-Pain in the joints, bones, and muscles. 9-Limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets

Question 19

Complication of Marphan syndrome

Answer 19

Complication of Marphan syndrome It most commonly affects the heart, eyes, blood vessels and skeleton.
Cardiovascular complications - Aortic aneurysm due to weak connective tissue - Aortic dissection. - Valve malformations.
Eye complications - Superiorly and temporally dislocation of lens. - Early-onset glaucoma or cataracts .

Question 20

Down syndrome  (Trisomy 21) :
The Causes:
Genotypes

Answer 20

1- Non disjunction

2- Translocation (4%)

3- Mosaic (1%)

—————
Non disjunction during meiosis of the gametes: resulting in 2 cells, one with 22 and the other with 24 ch. If normal cell with 23ch. fertilize the one with 24 ch.,the resulting zygote will have 47 ch.
2- Translocation (4%) Translocation of 21q to group D (13-14) or group G (21-22). Trisomy 21 patients with translocation has 46 ch. , one of them is abnormal containing 21q. The patient is phenotypically similar to regular type. One of the parents is usually carrier for translocation having 45 ch.and he is phenotypically free.
3- Mosaic (1%) Post fertilization non disjunction of one cell line while the other line divides normally.

Question 21

Recurrence risk of Down Syndrome:

Answer 21

The recurrence risk in general is 1% 1- Non disjunction type : The risk increases in old mothers ( more than 35 years). 2- Translocation type: — If the translocation in the affected parents is de novo occurrence , the risk of recurrence is negligible.
—If the translocation is of the inherited type, one of the parents is expected to be balanced translocation carrier with 45 ch. (either 14/21 , 22/21 or 21/21).
The presence of translocation interferes with normal segregation of chromosomes during meiosis and the translocation carrier individual may form balanced or unbalanced gametes ( as shown in the next slide).
if the translocation is on 21/21 , the recurrence risk rises to 100% (as shown)

Question 22

Clinical features of Down Syndrome

Answer 22

1- Mental retardation: IQ 25-50% 2-Microcephaly, brachycephaly and flat occiput. 3- Generalized hypotonia with umbalical hernia. 4-Short broad neck. 5- Lateral upward slopeof the eyes with epicanthal folds. The ear has over folding helix. The tongue is protruded and the nose is short with flat bridge.
6- The hand is short with incurving 5 th finger and transverse palmer crease. 7- The feet show wide gape between the 1 st and the 2
nd toe 8- Cardiac anomalies (septal defects) 9- Duodenal atresia (common). 10- Leakemia: 10-20 times more than general population. 11- Poorly developed genitalia.