SELECTED TOPICS IN GENETIC DISORDERS.

ByDr Abiodun Mark Akanmode

Table of Content.INTRODUCTION TO GENETICS.TURNER SYNDROME.KLINFELTER SYNDROME.FAMILIAL HYPER CHOLESTEROLEMIA.ALKAPTOURIA.NEUROFIBROMATOSIS.CYSTIC FIBROSIS.

INTRODUCTIONGenetics is the science of genes, heredity and

variations in living organisms.Genetics deals with the molecular structure and

function of genes, gene behavior, patterns of inheritance from parent to off springs and gene distribution and variation.

A genetic disorder is a disease that is caused by an abnormality in an individual's DNA. Abnormalities can be as small as a single-base mutation in just one gene, or they can involve the addition or subtraction of entire chromosomes.

TURNER SYNDROME.

TURNER SYNDROME: XO (45) (Monosomy X). Masculine Woman.

PATHOGENESIS: Many woman are only missing part of the other X chromosome not the whole thing.(the second X chromosome is responsible for oogenesis and normal development of the ovary)

SYMPTOMS: No menarche, sterility STREAK GONAD: Abnormal development of ovary, resulting in a fibrous

streak. Webbed neck They are short. Horseshoe kidney is often seen Coarctation of Aorta seen in 15% of cases. Bicuspid aortic valveCystic Hygroma (markedly distended lymphatic channels)HypothyroidismGlucose intolerence, obesity

Turner syndrome - short stature, webbed neck,

broad shield-like chest with widely spaced nipples

Cystic Hygroma in Turner syndrome (18 weeks) Streak gonads in Turner Syndrome

KLINEFELTER SYNDROME.

KLINEFELTER (XXY, XXXY, etc.)Hypogonadism found at puberty#1 cause of male infertilityNO retardation unless more X’s47, XXY 82% of the timeL----O----N-------------------G legs, atrophic testes,

small penis• SYMPTOMS: Gynecomastia, infertility, female pattern pubic hair,

testicular atrophy.

FAMILIAL HYPER CHOLESTEROLEMIA.

Cholesterol TRANSPORT across liver cell impairedso CHOLESTEROL BUILDUP IN BLOODPATHOGENESIS: Defect in LDL-Receptor.

Chromosome 19. HETEROZYGOTE: Cholesterol around 250-350 mg / dL

CHD by age 40. HOMOZYGOTE: Cholesterol > 600 mg / dL

Die of MI by age 30. SYMPTOMS:

Atherosclerosis at a very young age. Xanthomas: Fatty benign tumors, resulting from

accumulation of fat. Nodules of lipid-laden macrophages. (“FOAMY”)

FAMILIAL HYPERCHOLESTEROLEMIA.

ALKAPTOURIA.

ALKAPTONURIAThis is the first human inborn error of

metabolism to be discovered.It is an autosomal recessive disorder.

The enzyme homogentisic acid oxidase is lacking.

Thus homogenticic acid accumulates.BLACK URINEBLACK NAILS (OCHRONOSIS), SKINBLACK JOINT CARTILAGE (SEVERE

ARTHRITIS)

NEUROFIBROMATOSIS.

NEUROFIBROMATOSIS: Development of Neurofibromas, benign tumors of Schwann cell origin

NEUROFIBROMATOSIS TYPE I: aka Von Recklinghausen Disease.

EPIDEMIOLOGY:Relatively common, 1/3500 persons. PATHOGENESIS: defect in NF1 Gene, which

codes for a GTP ase-Activating Protein (GAP), involved in regulation of the Ras protein. Normally, the NF1 gene probably suppresses Ras. Defect allows Ras to continue unabated.

Neurofibromatosis 1 has three major features

1. Multiple neural tumors dispersed any where on or in the body ;

2. Numerous pigmented skin lesions, some of which are “ café au lait” spots and

3. Pigmented iris hamartomas, also called Lisch nodules.

SYMPTOMS:

Neurofibromas are soft Pedunculated tumors. There can be many or few of them.

Plexiform Neurofibromas are large, invasive neurofibromas.

NEUROFIBROSARCOMA appears in 3%-5% of patients, usually of plexiform type.

Cafe 'Au Lait Spots: Six or more such lesions, greater than 1.5cm each in adulthood.

Lisch Nodules: Pigmented nodules of iris, which are masses of melanocytes.

Skeletal lesions

Mental Status: Mild intellectual impairment sometimes, but not retardation.

Lisch Nodules in IrisIris Harmatomas

Muchas Gracias..Al final.