[Embryology] Chapter 16 — Urogenital System Clinical Correlates

"Wilms tumor"

"Pediatric kidney cancer usually presenting by age 5, caused by mutations in the WT1 gene on chromosome 11p13."

"WAGR syndrome"

"Wilms tumor, Aniridia, Gonadoblastoma, and mental Retardation, caused by a microdeletion on chromosome 11 spanning both the PAX6 and WT1 genes, located only 700 kb apart."

"Denys-Drash syndrome"

"Triad of renal failure, ambiguous genitalia, and Wilms tumor, associated with WT1 mutations."

"Renal dysplasia and agenesis"

"Spectrum of severe malformations that are the primary diseases requiring dialysis and transplantation in the first years of life."

"Multicystic dysplastic kidney"

"Numerous ducts surrounded by undifferentiated cells; nephrons fail to develop and the ureteric bud fails to branch, so collecting ducts never form."

"Autosomal recessive polycystic kidney disease (ARPKD)"

"Progressive disorder occurring in 1/5,000 births in which cysts form from collecting ducts; kidneys become very large and renal failure occurs in infancy or childhood."

"Autosomal dominant polycystic kidney disease (ADPKD)"

"More common disorder (1/500 to 1/1,000 births) in which cysts form from all segments of the nephron; usually does not cause renal failure until adulthood."

"Ciliopathies"

"A growing group of diseases, including ARPKD and ADPKD, caused by mutations in genes encoding ciliary proteins important for ciliary function."

"Townes-Brocks syndrome"

"Caused by mutations in the SALL1 gene, which regulates GDNF signaling; associated with renal agenesis."

"Renal-coloboma syndrome"

"Caused by mutations in the PAX2 gene, which regulates GDNF signaling; associated with renal agenesis and eye coloboma."

"Branchiootorenal syndrome"

"Caused by mutations in the EYA1 gene, which regulates GDNF signaling; associated with renal agenesis plus ear and branchial defects."

"Potter sequence"

"Anuria, oligohydramnios, and hypoplastic lungs resulting from bilateral renal agenesis (1/10,000 births); presents with a flattened face (Potter facies) and clubfeet due to uterine compression."

"Bardet-Biedl syndrome"

"A ciliopathy characterized by renal cysts, obesity, intellectual disability, and limb defects."

"Meckel-Gruber syndrome"

"A ciliopathy characterized by renal cysts, hydrocephalus, microphthalmia, cleft palate, absence of the olfactory tract, and polydactyly."

"Duplication of the ureter"

"Results from early splitting of the ureteric bud, which may be partial or complete."

"Ectopic ureter"

"Occurs when one of two ureteric buds moves down together with the mesonephric duct, resulting in a low, abnormal entrance into the bladder, urethra, vagina, or epididymal region."

"Pelvic kidney"

"A kidney that remains in the pelvis close to the common iliac artery because it failed to pass through the arterial fork formed by the umbilical arteries during ascent."

"Horseshoe kidney"

"Fusion of the lower poles of the kidneys, pushed together during ascent through the arterial fork of the umbilical arteries; found in 1/600 people; further ascent is halted by the root of the inferior mesenteric artery."

"Accessory renal arteries"

"Common vessels derived from persistence of embryonic vessels that formed during ascent of the kidneys; usually arise from the aorta and enter the superior or inferior poles of the kidneys."

"Urachal fistula"

"Occurs when the lumen of the intraembryonic portion of the allantois persists, causing urine to drain from the umbilicus."

"Urachal cyst"

"A cystic dilation that results when only a local area of the allantois persists and its lining retains secretory activity."

"Urachal sinus"

"Forms when the lumen in the upper part of the allantois persists and remains continuous with the urinary bladder."

"Exstrophy of the bladder"

"A ventral body wall defect in which bladder mucosa is exposed and epispadias is a constant feature; caused by failure of the lateral body wall folds to close in the pelvic region; occurs in 2/10,000 births."

"Exstrophy of the cloaca"

"A more severe ventral body wall defect than bladder exstrophy; involves altered urorectal septum development causing anal canal malformations and imperforate anus, plus widely spaced genital swellings; occurs in 1/30,000 births."

"Uterus didelphys"

"The most extreme form of uterine duplication, in which the uterus is entirely double, resulting from lack of fusion of the paramesonephric ducts."

"Uterus arcuatus"

"The least severe form of uterine duplication, in which the uterus is only slightly indented in the middle."

"Uterus bicornis"

"A relatively common anomaly in which the uterus has two horns entering a common vagina; normal in many non-primate mammals."

"Uterus bicornis unicollis with rudimentary horn"

"Results from atresia of one paramesonephric duct; the rudimentary side often does not communicate with the vagina, causing complications."

"Cervical atresia"

"Results when atresia involves both paramesonephric ducts at the cervical level."

"Vaginal atresia"

"Results when the sinovaginal bulbs fail to develop; a small vaginal pouch from the paramesonephric ducts usually surrounds the cervical opening."

"Double vagina"

"Results when the sinovaginal bulbs fail to fuse."

"Hypospadias"

"Incomplete fusion of the urethral folds causing abnormal urethral openings along the ventral aspect of the penis, near the glans, shaft, or base; occurs in 3-5/1,000 births, a rate that has doubled over the past 15-20 years, possibly linked to environmental estrogens."

"Epispadias"

"A rare abnormality (1/30,000 births) in which the urethral meatus is found on the dorsum of the penis; most often associated with exstrophy of the bladder."

"Micropenis"

"Occurs when there is insufficient androgen stimulation for growth of the external genitalia, usually from primary hypogonadism or hypothalamic/pituitary dysfunction; defined as 2.5 standard deviations below mean length."

"Bifid (double) penis"

"May occur if the genital tubercle splits."

"Disorders of sex development (DSD)"

"A spectrum of conditions in which sexual differentiation is atypical, since male and female development begins identically; genitalia may appear ambiguous."

"Ovotesticular disorder of sex development"

"Formerly called true hermaphroditism; both ovarian and testicular tissue are present, in any combination of ovary, testis, or ovotestis; genitalia are always ambiguous; karyotype is 46,XX in 70% of cases."

"46,XX disorders of sex development"

"Genetically female individuals exposed to excessive androgenic compounds that masculinize the external genitalia, causing ambiguity."

"Congenital adrenal hyperplasia (CAH)"

"The most common cause of ambiguous genitalia, accounting for approximately 60% of all DSDs; 90% of cases are due to 21-hydroxylase deficiency causing mineralocorticoid deficiency and increased androgens."

"11-beta-hydroxylase deficiency"

"A rarer form of congenital adrenal hyperplasia that causes biochemical effects and external genitalia changes similar to 21-hydroxylase deficiency."

"17-alpha-hydroxylase deficiency"

"A form of congenital adrenal hyperplasia causing decreased prenatal and pubertal sex steroids; affected females have no breast development or pubic hair; affected males have moderate to severe reduction in testosterone."

"46,XY disorders of sex development — isolated MIS deficiency"

"A rare disorder with no production of Müllerian inhibiting substance (MIS/AMH); genitalia are normal male, but remnants of the Müllerian system (uterus, uterine tubes) persist."

"Androgen insensitivity syndrome (AIS)"

"A lack of androgen receptors or failure of tissue response to receptor-dihydrotestosterone complexes in genetic males; testes and MIS are present so the paramesonephric system is suppressed, but external genitalia don't virilize."

"Complete androgen insensitivity syndrome (CAIS)"

"A form of AIS in which a short or poorly developed vagina is present; testes are often inguinal or labial with no spermatogenesis; 33% develop malignancies before age 50."

"Mild/partial androgen insensitivity syndrome (MAIS/PAIS)"

"Milder forms of AIS with varying degrees of virilization or ambiguous genitalia, including clitoromegaly or a small penis with hypospadias; testes are usually undescended."

"5-alpha-reductase deficiency (5-ARD)"

"A condition causing ambiguous genitalia in males due to an inability to convert testosterone to dihydrotestosterone; external genitalia may appear underdeveloped male or female with clitoromegaly."

"Klinefelter syndrome"

"The most common sex chromosome disorder (karyotype 47,XXY or variants), occurring in 1/1,000 males; features decreased fertility, small testes, decreased testosterone, and gynecomastia in ~33% of cases."

"Gonadal dysgenesis"

"A condition in which oocytes are absent and the ovaries appear as streak gonads; individuals are phenotypically female but may have varying chromosomal complements, including XY."

"Swyer syndrome"

"XY female gonadal dysgenesis resulting from point mutations or deletions of the SRY gene; individuals appear phenotypically female but do not menstruate or develop secondary sexual characteristics."

"Turner syndrome"

"A form of gonadal dysgenesis with karyotype 45,X; features short stature, high-arched palate, webbed neck, shield-like chest, cardiac and renal anomalies, and inverted nipples."

"Congenital indirect inguinal hernia"

"Occurs when the processus vaginalis remains open after birth, allowing intestinal loops to descend into the scrotum."

"Hydrocele"

"Occurs when obliteration of the processus vaginalis is irregular, leaving small cysts that later secrete fluid along the testis and/or spermatic cord."

"Cryptorchidism"

"Failure of one or both testes to descend into the scrotum, occurring in