Genetic Disorders

Congenital disorders caused by one or more abnormalities in the genome

Important cause of MR Higher frequencies among spontaneous

abortions and stillbirths abN. Of chromosomes and numbers

Causes Due to imbalance of genetic information Heredity (altered chromosome is passed

from parent to child ) New mutations or changes of the DNA The abnormality happens when either

the sperm or egg (germ cells) is created Soon after conception.

Changes in number of chromosomesMost people have 23 pairs of chromosomes, or 46

chromosomes in all. When the egg or sperm is made, the pairs split so that each egg or germ cell only contains 23 chromosomes. . 

Changes in chromosome structureSometimes the information contained in a chromosome

breaks up and the pieces reform in a different pattern. For example, a fragment of chromosome may break off and be lost during the formation of either the egg or sperm cell. A section of chromosome might also break away and ‘stick’ to another chromosome. 

Uniparental disomyUniparental disomy means the child inherited a particular

gene pair (both copies of the gene) from one parent only. This can cause a disorder if it is necessary for the child to have inherited one such gene from each parent. 

Chromosomal mosaicismNormally every cell in the body contains the same genetic information – all 46 chromosomes, designated as 46XX (female) or 46XY (male). A person who has chromosomal mosaicism has different numbers of chromosomes in different cells; for example, 46 in some cells and 47 in others.

Mitochondrial disordersMitochondria are like little batteries that make energy within each cell. The energy source is a chemical called adenosine triphosphate (ATP). Organs like the brain, heart and liver can’t survive without ATP.

Multifactorial disordersMultifactorial (involving several factors) disorders, such as many common birth defects or diseases like high blood pressure, are disorders caused by the environment interacting with the action of several genes. (This is also sometimes called polygenic inheritance.) For example, the birth defect spina bifida is caused by the action of several genes and also depends on the amount of folate in the mother’s diet during pregnancy (the environment). High blood pressure is influenced by a large number of genes, but also is influenced by a person's diet and salt intake.

Patau’s Syndrome (Trisomy 13)

• Cleft lip often midline• flexed fingers with polydactyly• ocular hypertelorism• bulbous nose• low-set malformed ears• small abnormal skull• cerebral malformation, especially

holoprosencephaly• Micropthalmia• cardiac malformations• scalp defects• hypoplastic or absent ribs• visceral and genital anomalies

Epidemiology: 1/10,000at risk with pregnancy of 31 years and

above

Edward’s Syndrome (Trisomy 18)

• Low birth weight• closed fist with index finger

overlapping the third digit and the fifth digit overlapping the fourth

• narrow hips with limited abduction

• short sternum• rocker-bottom feet• Microcephaly• prominent occiput• Micrognathia• cardiac and renal

malformations• MR

Many affected infants do not survive before birthApnea: may cause deathMed lifespan: 5-15 days ab

Down Syndrome (Trisomy 21)• Hypotonia• flat face; upward and slanted

palpebral fissures and epicanthic folds

• speckled irises (Brushfield Spots)• varying decrease of mental and

growth retardation• dysplasia of the pelvis• cardiac malformations and

simian creases• short, broad hands• hypoplasia of the middle phalanx

of 5th finger• intestinal atresia• high arched palate• Lifespan: up to 50y/o

• (only trisomy compatible with life• MC• IQ: 30-50 • Usually from mother’s egg (at risk with pregnancy of 35 years and above)

Mosaicism (Trisomy 8)

• Long face• high prominent forehead• wide upturned nose• thick everted lower lip• Microretrognathia• low-set ears• high arched, sometimes

cleft palate• Osteoarticular anomalies

are common, moderate MR

Mosaicism Term used to describe an individual who has two

different cell lines derived from a single zygote  a condition in which cells within the same

person have a different genetic makeup. This condition can affect any type of cell, including: Blood cells Egg and sperm cells (gametes) Skin cells

caused by an error in cell division very early in the development of the unborn baby

Less severe

Kllinefelter’s Syndrome Extra ‘x’ chromosome Affects 1-2/1,000 males Males are affected Mentally disadvantage, sterile male

with underdeveloped testes, broader hips, scant body hair, and enlarged breasts

Turner’s Syndrome One of the MC monosmies Loss of part or all of one of the sex

chromosomes 1 /4000 liveborn females or 1/8000 5-10% have some Y chromosome

material in all or some cells Short stature Underdeveloped gonads Virtually no ovaries Reproductive sterility Web neck Underdeveloped breasts and

widely spaced nipples N intelligence

Chromosomal Deletion 4p- Wolf-Hirschhorn syndrome 5p- Cri-du-chat Syndrome 9p- 13p- 18p- 21p-

Chromosomal Deletions 7p11.23 8q24.1

11p13 15q11-13 15q11-13(mat) 16p13-17p11.2 17p13.3 20p12 22q11.2

WilliamsLanger-Giedion or tricho-rhino-phalangeal, type II WAGRPrader- WilliAngelmanRubinstein Taybi Smith- MagenisMiller-DiekerAlagille syndromeVelocardiofacial-DiGeorge syndrome