This section of notes covers abnormalities in kidney. There is now a separate notes page for Genital Abnormalities. The kidneys filter and excrete waste body fliuds and they function before birth. In addition to abnormalities of kidney development, there are a number of abnormalities associated with either obstruction of the ureters or abnormal cloacal septation that can impact upon the fetal kidney.
Horseshoe Kidney (Image: Calori, L. Mem. Accad. Sci. Istituto di Bologna S.46:73-83, 1884.)
The "figures" referred to on this page are on posters in the practical classroom.
Page Links: Introduction | Australian Statistics 1981-1992 | Self Assessment Questions | OMIM Database | Renal Agenesis | Polycystic Kidneys | Multicystic Kidney | Urinary Tract Obstruction | Congenital Hydronephrosis | Prune Belly | Horseshoe Kidney | Exstrophy of the Bladder | Wilms Tumour | Urorectal Septum Malformation | Diabetes Insipidus |
Reproductive: See Genital Abnormalities
Renal and Reproductive Abnormalities
About Data shown as a % of all Major Abnormalities based upon published statistics using the same groupings as CMA 81-92. (More? All system statistical data as graphs)
Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ. Renal Aplasia in Humans Is Associated with RET Mutations. Am J Hum Genet. 2008 Feb;82(2):344-51.
" In animal models, kidney formation is known to be controlled by the proteins RET (REarranged during Transfection protooncogene), GDNF, and GFRA1. We assayed for mutations in these genes in 33 stillborn (human) fetuses that had bilateral or unilateral renal agenesis (29 subjects) or severe congenital renal dysplasia (4 subjects). Mutations in RET were found in 7 of 19 fetuses with bilateral renal agenesis (37%) and 2 of 10 fetuses (20%) with unilateral agenesis."
In the complete form the child is not viable and dies within a few days of birth.
Features associated with this anomaly are:
(Figure 1). The ears are low slung and simple, the mandible is small, the nose flattened and the eyes exhibit Pre-epicanthic folds (Figure 2). This is a horseshoe shaped flap of skin from the upper lid to the cheek in front of the epicanthus. (Downs syndrome has an epicanthic fold). Note that the genesis is occasionally incomplete allowing survival (e.g.) Figure 2. Causal factors are largely unknown although there is some familial predisposition. There has been a recent article (1) describing a mutation in an enzyme, heparan sulfate 2-sulfotransferase, that generates a similar phenotype in the mouse.
Note that upper G.I.T. obstruction is associated with POLYHYDRAMNIOS whereas failure of fetal micturition is associated with OLIGOHYDRAMNIOS with consequent firm uterine moulding on the fetus, leading to facial, locomotor and palatal deformities.
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This is a diffuse cystic malformation of both kidneys with cystic malformations of the liver and lung etc. often being associated. There is often familial disposition with this malformation. Autosomal dominant PKD disease has been recently identified at mutations in 2 different human genes encoding membrane proteins, possibly channels (1, 2). See also recent article on PKD1 expression through development in the mouse.
There are 2 types:
See also UNSW Pathology- Specimen 1340092 Polycystic Kidneys
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There is no functional kidney tissue present in the kidney and it is replaced by a multilocular cyst. This is non-familial and is produced by atresia of a ureter and is always unilateral.
The figure shows a micturating urethrogram and shows a valve obstruction (arrow) with dilatation of the urethra between the valve and the bladder. This type of pre-natal obstruction produces gross hydronephrosis and hydroureter before birth.
The X ray above shows gross dilatation of the pelves and ureters and there is extensive destruction of renal tissue.
Usually due to partial or complete obstruction at the pelvi-ureteric junction, leading to grossly dilated renal pelvis and there is extensive renal damage before birth.
This may be familial, may be lateral, and is most commonly an intrinsic defect in the wall of the ureter (structural or functional). The less severe cases may be salvaged by reconstruction of the pelvi-ureteric junction.
The condition was first described by Frolich (1839) and then called "prune belly syndrome" as a descriptive, because the intestinal pattern is evident through the thin protruding abdominal wall in the infant (Osler, 1901).
Survival of the prune belly child depends on the number of functioning remaining nephrons at birth and the operability of the obstruction.
In some cases there are vestiges of muscle in the abdominal wall and it is not known whether this represents (a) destruction of muscle, or (b) failure of development of muscle. The causes of this malformation are little known, but maternal therapy with estrogens in the first trimester has been implicated frequently.
The Triad is:
Question: Does estrogen possibly inhibit the development of the male bladder outflow and genital system?
1. Frolich, F. Der Mangel der Muskeln, insbesondere der Seitenbauchmuskeln. Dissertation: Wurzburg (pub.) 1839.
2. Osler, W. Congenital absence of the abdominal muscles with distended and hypertrophied urinary bladder. Bull. Johns Hopkins Hosp. 12: 331-333, 1901.
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(Image: Calori, L. Mem. Accad. Sci. Istituto di Bologna S.46:73-83, 1884.)
In the horseshoe kidney there is fusion of the lower poles of the kidney.
During migration from the sacral region the two metanephric blastemas can come into contact as shown in Figure 14 mainly at the lower pole. The ureters pass in front of the zone of fusion of the kidneys. The kidneys and ureters usually function adequately but there is an increased incidence of upper urinary tract obstruction or infection.
Some horseshoe variations have been described as having associated ureter abnormalities including duplications.
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|A rare disorder with exposure and protrusion of the bladder and exposure of ureteric orifices. This is a deformity of the anterior abdominal wall and
there can be an associated bilateral inguinal hernia and externally rotated thighs.
The deformity is non-familial, of no known cause and is obvious at birth. The malformation produced incontinence, urine dribbles on the mucus membrane of the everted bladder.
The surgical reconstruction is complex and requires simultaneous repair of the bony pelvis and covering of the bladder and bladder neck. The epispadiac urethra is reconstructed later.
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Wilms' tumor (also called nephroblastoma) is the most common type of kidney cancer affecting children. It is named after Max Wilms, a German doctor who wrote one of the first medical articles about the disease in 1899. WT1 encodes a zinc finger protein expressed as distinct isoforms. Both constitutional and somatic mutations disrupting the DNA-binding domain of WT1 result in a potentially dominant-negative phenotype. (More? List Pax/Wilms Tumour and Pax2/Kidney development).
Urorectal septum malformation thought to be a deficiency in caudal mesoderm which in turn leads to the malformation of the urorectal septum and other structures in the pelvic region. Recent research has also identified the potential presence of a persistent urachus prior to septation of the cloaca (common urogenital sinus).
Clinically the condition is described as a urorectal septum malformation sequence (URSMS): female pseudohermaphroditism; ambiguous external genitalia; imperforate anus, vagina, and urethra; renal, colonic, and lumbosacral anomalies.
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Links: 2007 Review Article
In diabetes insipidus there is an excretion of large amounts (up to 30 litres/day) of a watery urine and an unremitting thirst. The disorder is generally related to the hormone antidiuretic hormone (ADH, also called vasopressin its synthesis, secretion, receptors and signaling pathway.
Nephrogenic Diabetes Insipidus
Due to genetics, kidney disease, high calcium or drugs. Two known genetic mutanions are in the genes for the ADH receptor or in the genes for aquaporin-2. (More? Polycystic Kidneys)
Central Diabetes Insipidus
Note the two other main forms of diabetes mellitus and gestational diabetes are disorders of glucose regulation associated mainly with insulin and the pancreas. These other forms of diabetes can cause diabetic nephropathy, thought to result from uncontrolled high blood sugar damaging the kidney. In some cases, your genes or family history may also play a role. Not all persons with diabetes develop this condition(More? Diabetes Mellitus | Maternal Diabetes)
There is now a separate notes page for Genital Abnormalities.
Genital abnormalities fall into several categories: chromosomal, hermaphroditism, gonadal dysfunction, tract abnormalities, external genitalia and gonadal descent. (More? Genital Abnormalities)
Search Feb 2006 "postnatal human development" ?? reference articles of which ?? were reviews.
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See also UNSW Embryology References Page
Polycystic ovary syndrome (PCOS) or Stein–Leventhal syndrome (1930s researchers) a metabolic syndrome with many other symptoms, ovarian cysts arise through incomplete follicular development or failure of ovulation. For review see Norman RJ, Wu R, Stankiewicz MT. Polycystic ovary syndrome. Med J Aust. 2004 Feb 2;180(3):132-7.