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
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."
(More? Molecular)
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.
OMIM Database Entry-191830 UROGENITAL ADYSPLASIA, HEREDITARY
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.
Medline
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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:
OMIM Database Entry- 173900 POLYCYSTIC KIDNEYS (about this entry)
See also UNSW Pathology- Specimen 1340092 Polycystic Kidneys
Medline
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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.
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Urethral Valves
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.
Congenital Hydronephrosis
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?
References:
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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In the horseshoe kidney there is fusion of the lower poles of the kidney.
Horseshoe Kidney (Image: Calori, L. Mem. Accad. Sci. Istituto di Bologna S.46:73-83, 1884.)
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.
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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.
Search Pubmed Now: exstrophy+of+the+bladder[TITL]
Links: OMIM 1999 Entry EXSTROPHY OF BLADDER | Association for the Bladder Exstrophy Community | Atlas of Fetal MRI - Bladder Extrophy |
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. (See the List Pax/Wilms Tumour and Pax2/Kidney development)
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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).
Search Pubmed Now: Urorectal Septum Malformation
Links: 2007 Review Article
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.
Turner's Syndrome: Monosomy XO, 99% non-viable embryos, fail to sexually mature at puberty.
Klinefelter's Syndrome: 47, XXY, begin normal male, become infertile. Features tall, mental dullness, behaviour problems
Males 46, XX, Develop as male, infertile adults, portion of SRY gene located on one X. (More? Genital Abnormalities)
True: 46,XX, Gonads both ovary and teste tissues, Ovotestes or ovary and testes
Male Pseudohermaphrodites: 46,XY, Gonads of one sex, external genitalia of opposite, Various causes
Female Pseudohermaphrodites: 46,XX, Gonads are ovaries, external genitalia ambiguous, Hyperplastic adrenals secrete androgens
(More? Genital Abnormalities)
Gonads fail to develop properly.
Gonadal Dysgenesis: 46,XX, Swyer's syndrome
Mixed Gonadal Dysgenesis: 45,X/46,XY
Primary Hypogonadism: 46,XX, affected females
Primary Hypogonadism: Defective anterior pituitary production of gonadotropin, lack of gonadotropin-releasing hormone
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.
(More? Genital Abnormalities)
Many different forms
Uterine: Associated with other anomolies
Vagina: Agenesis, atresia See endocrine lecture DES
Ductus Deferens: Unilateral or bilateral absence, failure of mesonephric duct to differentiate
(More? Genital Abnormalities)
Cryptorchidism is an abnormality of either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males. Descent may complete postnatally in the first year, failure to descend can result in sterility.
Hydrocele a fluid-filled cavity of eiter testis or spermatic cord, where peritoneal fluid passes into a patent processus vaginalis.
(More? Genital Abnormalities)
Hypospadis most common penis abnormality (1 in 300) resulting from a failure of male urogenital folds to fuse in various regions. (More? Genital Abnormalities)
A list of results from a search for "gonad" of the OMIM Database below which are shown some specific abnormalities. OMIM Database Entries List- Gonad
Undescended Testis - 219050 CRYPTORCHIDISM
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Search Feb 2006 "postnatal human development" ?? reference articles of which ?? were reviews.
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A Selected List of References from March 1999 search results for Selected Research Articles and Reviews | sry/review/2years | bladder development
<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.
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The kidney goes through several stages of development before establishing the mature kidney.
The functional unit of the kidney, the nephron, develops through a classical epithelial/mesenchyme type of interaction.
The gonads have quite different origins and developmental features, but are closely physically associated. (More? Reproductive System - Abnormalities)
Please email Dr Mark Hill if you wish to make a comment about this current project.