jslum.

com | Medicine
Genetics of Genitourinary Tract

Genetic Sex Ambiguous Genitalia

Male, Female Embryos – Identical Intersex – Neither Boy or Girl
Internal, External Genitalia – Until 7th or 8th week of Pregnancy Causes
Embryos – 2 Gonads Reproductive organs, Genitals associated arise from Same Fetal Tissue
Undefined – Early weeks Disrupted Genetic Process that cause Fetal Tissue to become Male/ Female
Later Develop into Ovaries or Testicles Disrupted Hormonal Sexual Differentiation
Based on whether embryo carry the Y Chromosome
Classification of Ambiguous Genitalia
Y Chromosome True Hermaphroditism
Carry the gene responsible for Testicle formation Both Male, Female Genitalia, Internal Reproductive Organs
Secretion of Testosterone Gonadal Dysgenesis
Determine Internal, External Genitalia development Internal organs 1° Female
Young Embryos External Genitals – vary between
Have both Male, Female Genital structures • Normal Female
• Normal Male
Secretion of Testosterone • Underdeveloped Gonad
Regression of 1 set of Internal Structures Some cells in body
Distinct Male – Prostate, Vas Deferens • Single X Chromosome
Distinct Female – Uterus, Fallopian Tubes, Vagina • XY Chromosome
Absence of Male Hormones Pseudo Hermaphroditism
(rather than presence of female ones) Questionable External Genitalia, but only 1 gender’s reproductive organs
Cause External, Internal Genitalia to become Female Male Female
Sexual differentiation Deficiency of Male Sex Hormones Virilization
Chromosomal Abnormality Exposure to ↑ levels of Male
SRY Gene Absent, Underdeveloped Testes Hormones
Sex Determining Region – Y gene cause Androgen deficiency
Sexual Differentiation gene Clinical
Y chromosome High Pitched Voice
Testicle Determining Factor (TDF) Poor Muscle Development
Other genes – Sexual Differentiation Underdeveloped
• Penis
• Testes
• Scrotum
Sparse
• Pubic hair
• Underarm hair
Abnormally long
• Arms
• Legs
Androgen Deficiency can be treated Female Pseudohermaphroditism
with Testosterone
Chromosomal Sex Determination Congenital Adrenal Hyperplasia (CAH)
1st 6 weeks – Embryo Deficiency of enzyme (2 1 Hydroxylase)
Cells that develop into Gonads, Internal Ducts, External Genitalia - Bipotential Autosomal Recessive Gene
Presence of SRY Absence of SRY Male Female
Develops into Testicle Ovary Results Normal Genitals at Birth Enlarged Clitoris
Messages Premature Sexual Development Normal Internal Reproductive Tract
Sex Chromosomes → Gonads → Hor mones Tall as Children Structures
Lack of Testosterone Cellular Receptors Short as Adults Develop Male Characteristics
Body is unable to respond to the hormones Tall as Children
Short as Adults
Gender Determination by Chromosomes
X+X X+Y X+0 X+X+Y Identification of Cause
Female Male Female Male Physical Examination
Turner Klinefelter Buccal Smear
Syndrome Syndrome Blood Tests (Chromosome Pattern)
Ultrasound of Abdomen, Pelvic
Genitogram (special X-ray test)
Tissue analysis
Hormone tests

Treatments
CAH, Pseudohermaphroditism
Potentially fertile once underlying hormonal imbalance is corrected
Girls with Testicular Dysgenesis
Gonads can be removed
Uterus left in place
(nurture an implanted embryo conceived in laboratory using modern ART)
(ART – Assisted Reproductive Techniques)
Boys having at least 1 testicle
Have potential to be Normal
 jslum.com | Medicine

Urinary Tracts Defects Polycystic Kidney Disease (PKD)

Genitals, Urinary Tract Abnormalities – most common birth defects Inherited disorder
affecting as many as 1 in 10 babies Growth of numerous cysts in Kidneys
Defects affect ↓ Kidney function, Kidney Failure (often)
Kidneys Can be Surgically corrected
Ureters
Bladder
Urethra
Causes – Genital, Urinary Tract Defects
Inherited from parents (have disorder, carry gene)
Specific causes – unknown
Genetics, Environmental Factors (play various roles in development)
Autosomal Dominant (90%) Autosomal Recessive
Renal Agenesis Common – All Ages Rare – Affects Children
Absence of 1 or 2 Kidneys Cysts sometimes develop before Birth
Most severe manifestation of an Autosomal Dominant condition Inherited from a parent (with disease) Inherited from both parents
Fetus that has no kidneys (unaffected) pass along gene for the
Cannot produce urine (major part of amniotic fluid) disorder to their child
Amniotic fluid – crucial for Normal Fetal Lung Development
Lack of Amniotic Fluid Bladder Exstrophy
Abnormal Facial Features Malformation of Bladder
Limb defe cts Bladder is Turned Inside Out
Located Outside of the Abdome n
Boys ↑ (5X)

Epispadias
Rare congenital malformation of Urogenital Apparatus (Male, Female)
Consists of a defect of Dorsal wall of Urethra
Accompanies Bladder Exstrophy
Can also occur by itself
Can be Surgically corrected
Boys Girls
Urethra is short Clitoris may be split
Split with an opening on upper Urinary opening is abnormally placed
surface of Penis

Hypospadias
Birth defect of Urethra in Male
Abnormally placed Urinary Meatus (opening)
Hydronephrosis Cause – Unknown (Genetic association)
Swelling of 1 or 2 Kidneys Urethra does not extend to tip of penis
Accumulation of Urine that cannot flow out of Kidneys Opening of Urethra is located somewhere along underside of penis
Blockage in Urinary Tract
Affected boys should not circumcised
Surgically corrected
Foreskin used to help surgically repair the defect
Can become life threatening before birth
 jslum.com | Medicine

Genetic causes of Kidney Stones

Hypercalciuria
Most common cause of Kidney Stone
Urine - ↑ levels of Calcium
↑ Urinary Ca Concentration trait is passed from generation to generation
Different genes involved
Hyperoxaluria
Genetic disorder (presents often during Childhood)
↑ Urinary Oxalate levels
Treatment – Liver +/- Kidney Transplant
Type I (1° Hyperoxaluria) Type II
Deficiency of Deficiency of
Alanine Glycoxylate Aminotransferase D-glyceric Dehydrogenase
Cystinuria
Genetic disorder
↑ Urinary Cystine concentration
Multi Endocrine Neoplasm (MEN)
Rare Genetic disease
Associated with
• Hyperparathyroidism
• Kidney stones

Diagnosis of Urinary Tract Defects

Physical Examination
Ultrasound
CT
Nuclear scan
Intra venous Urography
Cystoscopy

Attempts to ↑ Quality of Man

Improve Individuals already existing in Society
Improve Mankind by ensuring Improved Progeny