General Pathology

1. Prof.Dr.
Khalil Hassan Zenad
Aljeboori
Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
GENETIC DISEASES
Lecture 15

2. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
Types of genetic diseases:
I- Chromosomal abnormalities
II- Inherited disorders (gene abnormalities)
I- Chromosomal abnormalities:
A. Abnormalities of Chromosome number
1.Aneuploidy:
in which a Chromosome number if it is not exact multiple of the haploid (23) e.g.45 or 47. The presence of three
instead of unusual pair of chromosome known as trisomy e.g.: mongolism of Down’s syndrome.
Origin of aneuploidy:
Trisomy and monosomy is attributed to an error-non disjunction in either first or second cell division of meiosis in
which two homologons Chromosomes fail to separate, both chromosome for that pair enter one daughter cell
nucleus. The one cell have 24 chromosome and other 22 on their fertilization by normal germ cells the zygotes formed
will have 47 and 45 chromosomes respectively , the former being Trisomic and later monosomic for that
chromosome, non-disjunction can occur during mitotic cell division.
2.Polypoidy:
a Chromosome number is a polypoidy if it is multiple of basic haploid (23) other than normal diploid (46) number e.g.:
69 or 92 this seen in chromosomes of neoplastic tissues.
Origin of polypoidy:
An error in the formation of spindle mechanism during meioses after duplicated chromosome material and before
the complete cell division.

3. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
B. Abnormalities of Chromosome structure:
In which chromosome breakage, the common type of chromosomal structured
abnormalities include:
1.Deletion: is the loss of a segment of a chromosome, this deleted chromosome participates
in subsequent cell division only if centromere is present.
2.Duplication: is the inclusion of the extra segment of chromosome within a chromosome.
3.In version: this follow detachment of a segment of chromosome with recombination within
chromosome in an inverted position.
4.Iso chromosome: are produced when division at the centromere take place at right angle
to the long axis of chromosome instead parallel to it the result on chromosome of two short
arms and other of two long arms. It is partly a duplication and partly a deletion.
5. Translocation (exchange), segment of chromosome exchange to non homologous
chromosome.

4. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
C. Chromosomal mosaicism:
Is the presence of same individual of two kinds of chromosomes constitution derived from
single zygote. Some Mongols are mosaics and have tissue with 46 and 47 chromosomes
several patients with Turner’s syndrome have xo and xx cell lines.
Causes of Chromosome abnormalities: Several factors may be important:
1.Radiation- cause chromosome deletion and translocations
2.Virus infection E.g. measles produce fragmentations of chromosomes
3.Late maternal age.
Major factor incidence of Down’s syndrome, more frequent in older than younger women in
which non-disjunction occur in older women.

5. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
Clinical conditions due to chromosomal abnormalities
1.Autosomal abnormalities:
Down’s syndrome-mongolism or G trisomy characterized by mental retardation, a typical facies,
wide spread eye, epicanthic fold, short neck, flattened occiput broad flat hands with short incurving
fifth digit, abnormal dermatoglyphic pattern, ventricular and atrial septal defect, esophageal,
duodenal atresia, tracheoesophageal fistulae.
2.Sex chromosome abnormalities:
Turner’s syndrome_ ovarian dysgenesis or monosomy X has three characteristic:
a.Sexual infantilism: manifested by primary amenorrhea, lack of breast development with
widely spaced nipples, scanty sexual hair, infantile external genitalia, uterus, fallopian tube, streak
gonads which have no ovarian follicles.
b.Short stature- rarely reach height greater 5 feet.
c.Congenital anomalies: webbing of neck, congenital lymphedema of extremities and
coarctation of aorta and horse shoe kidney.

6. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
Multiple X syndrome in women:
The Triple_X syndrome characterized by mental abnormalities with slight under developed secondary
sex Character with secondary amenorrhea the usual karyotype is 47 with trisomy of x_ chromosome
(47/xxx) but occasionally chromosome 48 with four x sex chromosome (48/xxxx)
Klinefelter’s syndrome
This is male are:
a.Small azoospermic testes with sclerosing tubular degeneration interstitial hyperplasia.
b.Bilateral gynaecomastia, eunuchoid bulld, sprase sexual hair and beard growth, high urinary
gonadotrophine with low 17_ketosteroid excretion.
c.Mild intellectual subnormality-men have chromatin positive and have 47 chromosomes with sex
chromosome complement of xxy. Occasionally patient have xxxy or xxxxy karyotypes and a few may
be mosaics xxy/xx,xxy/xy
The yy syndrome
Individual with this syndrome have mild mental defect with violent and aggressive behavior and usually
taller than 6 feet. They have xyy karyotypes and occasionally xyyy, xxyy or xxxyy.
3.Chromosomal abnormalities and abortion: about 20% of abortion occur spontaneously in first 3
months of pregnancy due to chromosomal abnormalities in the fetus.
Many of these abortuses are triploids, XO or D trisomies.
4.Chromosomal anomaly and leukemia a characteristic anomaly- the Philadelphia chromosome
(Ph) is found in leukocytes of patients with chronic granulocytic leukemia. This chromosome marker
appear to be deleted chromosome number 21.

7. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
A. Pattern of inheritance: the pattern within families of single gene inherited disease are determined
by whether the mutant genes located on one of the autosome or on the X chromosome by whether the
gene in single dosage (heterozygous) or in double dosage homozygous and by the whether the trait
is dominant or recessive.
1.Autosomal dominant inheritance: is less severe than autosomal recessive condition. The
abnormal gene is located on one of a pair of autosomes.
• Features:
1.Trait appears in every generation unless it has arisen as a fresh mutation.
2.Affected person transmit the trait to half their children.
3.Male and female equally effected.
4.Unaffected person cannot transmit the condition to other condition.
•Diseases due to dominant inheritance:
Achondroplasia, brachydactylia (short finger), huntington’s chorea, marfan’s syndrome, familial
polyposis, multiple neurofibromatosis and tuberous sclerosis.
II- Inherited disorders (abnormal genes)

8. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
2. Autosomal recessive inheritance:
This disease is expressed in person who receive gene from both his parents and so is homozygous
for it.
• Features:
1.Condition appears in one quarter of brothers and sisters.
2.Parents and of spring are normal.
3.Male and female equally affected.
4.Parents of affected individuals often consanguineous.
• Diseases due to recessive in heritance
Many errors of metabolism e.g.:
Phenylketonuria, homocystinuria, alcaptonuria, cystic fibrosis, morgquio’s diseases and congenital
adrenal hyperplasia.

9. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
3. Sex-linked inheritance:
Sex- linked gene may be x-linked or y-linked. The only condition of y-linked gene is the hairy ear trait
transmitted from male to male (Holandric inheritance) x-linked gene have more clinical significance.
• X-linked recessive inheritance: the inherited disease is expressed by all males who have the gene
and only by female who are homozygous.
• Features:
1.Female only rarely affected
2.If the condition is lethal as in Duchenne type of muscular dystrophy transmission always through
carriers female.
3.Half of the sum of carriers are affected and half of their daughters are carriers.
4.Never male to male transmission.
• Diseases due to x-linked recessive inheritance:
Progressive muscular dystrophy, hemophilia, color blindness.
• X-linked, dominant inheritance:
Vitamin D-resistant rickets.

10. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
4. Sex-limited traits:
A trait which is sex limited appear in only one sex-baldness is sex limited
appearing usually in male.
5. Multifactorial or polygenic inheritance:
Many common diseases or anomalies which are not inherited in a dominant
or recessive manner nevertheless show some evidence of measure of genetic
inheritance. The disease may be result of several genes an additive affect or
produced by an interaction of genic and environmental factors.
• Diseases due to multifactorial inheritance:
pyloric stenosis, hare-lip with/Without cleft palate and congenital dislocation of the hip.

11. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
•Diabetes mellitus:
Hereditary-the usual pattern of inheritance described suggests the participation of single recessive trait with
incomplete penetrance but this evidence is not conclusive.
•Galactosemia:
Nature a familial disorder of the galactose metabolism.
Inheritance by a single autosomal recessive gene.
Etiology:
Due to deficiency of galactose-1 phosphate uridyl transferase.
The deficiency can be demonstrated in erythrocytes of patients and partially detected in heterozygotus carrier.
Clinical manifestation:
Appear in early infancy and include nutritional failure with vomiting, diarrhea, loss of weight,
hepatospleenomegally, cataract, mental retardation.
Laboratory findings:
1. Elevation of blood galactose.
2. Galactosuria, albuminuria, amino acid urea.
3. Deficient erythrocytes galactose-1 phosphate uridyl transference.
B. Inherited metabolic disorders:
I-disorder of carbohydrate metabolism

12. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
Nature:
Collection of distinct diseases resulted from primary abnormalities of
glycogen metabolism and resulting in the accumulation of glycogen in
the tissue.
Inheritance: by single autosomal recessive gene
Glycogen storage disease.

13. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
• Phenylketouria:
Nature: caused by deficiency of enzyme phenylalanine hydroxylase resulting in accumulation of
phenylalanine and its abnormal metabolites (demonstrable in liver and kidney)
Inheritance: autosomal recessive, clinically include severe mental retardation, convulsions,
eczematous skin lesion, deficiency of pigmentation of skin and hair.
• Alcaptonuria:
Nature: one inborn errors of metabolism described by Garrod 1908.
Inheritance: autosomal recessive.
Etiology: deficiency of enzyme homogentisic oxidase prevent break down of homogentisic acid
and cause its accumulation in serum and excretion in urine.
Clinical features:
Homogetisic aciduria, ochronosis (pigmentation of cartilage and other connective tissues), arthritis
in later years.
II-disease of amino acid metabolism

14. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
• Albinism:
Nature: inherited disorder of melanin metabolism resulting in decrease or
absence of pigment in skin, hair, eyes possibly due to defect in
tyrosinase.
Clinical manifestation:
1. Occulocutaneous albinism- usually autosomal recessive.
2. Ocular albinism-x-linked recessive
3. Localized cutaneous albinism autosomal dominant some time
associated with deaf-mutism.
• Familial goiter.

15. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
III- Disorders of lipid metabolism:
Nature: abnormal increase in the plasma of various lipid components
including:
• Hypertriglyceridemia:
Excessive chylomicrons in plasma, waxy skin, visible lipemia of retina, eruptive xanthomata and in childhood, spasm
of abdominal pain, hepatosplenomegally. It is autosomal recessive_ inherited character.
• Hypercholesterolemia:
familial disorder characterized by raised plasma cholesterol and in many patients associated with xanthoma
tuberosum and tendinosum.
There is risk of ischemic heart disease and some cases aortic stenosis.
Inheritance: it is familial is inherited as an autosomal dominant characteristic with incomplete expression in the
heterozygote.
• Hypercholesterolemia with hypertriglyceridemia:
Characterized by abnormal high plasma concentrations of both cholesterol and triglycerides, probably a
heterogeneous group of disorders.
Xanthomata may appear and moderate increase risk of ischemic heart disease in affected patients.
Abnormal glucose tolerance often found inheritance is probably multifunctional with genetic and environmental
factors playing a part.
The condition improved by low carbohydrate diet.
• Secondary hyperlipemia
may be caused physiological postprandial state, pregnancy, hyperthyroidism, obstructive jaundice, biliary cirrhosis,
glomerulonephritis, lipoid nephrosis and diabetes mellitus.

16. Copyrights©2017lAliraqiaUniversitylDentistrylPathologylProf.Dr.KhalilHassanZenadAljeboori.
Abnormal accumulation of fatty substances in reticular cells, histiocytes,
often congenital or familial, the main fatty materials or lipoidosis includes:
1. Guachers disease- lipoid substances in cerebroside (kerasin) the organ
affected spleen, bone marrow, skin, brain.
2. Neiman-pick disease. Phospholipid in reticuloendothelial, epithelial cells
and connective tissue.
3. Amaurotic family idiocy-Phospholipid in glial cells-ganglion cells in
central nervous system.
4. Xanthomatoses: lipid involvement of skeletal muscles, bone, marrow,
lung.
5. Other types of xanthomas (cholesterol) in skin, eyelids, tendon.
IV-lipid storage disease

17. PRESENTATION ENDS
Copyrights © 2017 l Aliraqia University l Dentistry l Pathology l Prof.Dr.
Khalil Hassan Zenad Aljeboori.
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