Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype) (Gribouval et al., 2005). Absence or ... Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype) (Gribouval et al., 2005). Absence or paucity of differentiated proximal tubules is the histopathologic hallmark of the disorder and may be associated with skull ossification defects.
Allanson et al. (1983) described 2 stillborn females born consecutively of a nonconsanguineous Chinese couple. Both had the Potter syndrome resulting from oligohydramnios and showed a seemingly unique histologic change in the kidneys. Normal proximal convoluted tubules were ... Allanson et al. (1983) described 2 stillborn females born consecutively of a nonconsanguineous Chinese couple. Both had the Potter syndrome resulting from oligohydramnios and showed a seemingly unique histologic change in the kidneys. Normal proximal convoluted tubules were absent and all tubules appeared abnormally developed, primitive and reminiscent of collecting tubules. The father had suffered from 'minimal change' glomerulonephritis. Swinford et al. (1986) described a second nonconsanguineous family of northern European and American descent in which 2 males and 1 female died with oligohydramnios sequence and pulmonary hypoplasia. The renal tissue in these children demonstrated abnormally developed, primitive renal tubules and interstitial fibrous connective tissue. Schwartz et al. (1986) described male and female sibs with congenital renal tubular immaturity. MacMahon et al. (1990) reported a typical case in an infant born of unrelated parents and reviewed 12 previous cases distributed in 5 families. Russo et al. (1991) reported an infant with this disorder who survived for 15 days after birth. The infant also had acrocephalosyndactyly of the Saethre-Chotzen type (101400), which was present in other members of the family. Allanson et al. (1992) reported an additional 9 cases from one pediatric center. Early prenatal diagnosis may be difficult because amniotic fluid volumes have been shown to be normal in affected pregnancies before 22 weeks' gestation. Late second trimester sonographic demonstration of oligohydramnios, with structurally normal kidneys, should suggest the diagnosis and the need for detailed postmortem pathologic examination for this disorder, which may not be as rare as was previously thought. Ariel et al. (1995) described a family in which consanguineous Palestinian Muslim Arab parents had 3 affected children. Microdissection of the nephrons in a male infant who died 30 hours after birth showed marked hypoplasia of all segments of the nephron, from the glomerulus to the collecting tubule. The authors suggested that hypoplasia of the distal parts of nephron, as well as the proximal convoluted tubule, is characteristic for this disorder. McFadden et al. (1997) reported 2 cases of renal tubular dysgenesis, both of whom had calvarial hypoplasia. They noted that 6 of the 24 cases reported by Allanson et al. (1992) had associated microcephaly, underdeveloped cranial bones, or widely patent fontanels, and that a number of other reported cases had skull abnormalities. McFadden et al. (1997) suggested that skull abnormalities are a common component of the inherited form of renal tubular dysgenesis, as they are in the acquired form of renal tubular dysgenesis associated with maternal use of angiotensin-converting enzyme (ACE; 106180) inhibitors. McFadden et al. (1997) concluded that skull abnormalities may be important in suggesting the diagnosis of renal tubular dysgenesis. Uematsu et al. (2006) reported a Japanese female infant with renal tubular dysgenesis. The patient was born at 35 weeks gestation with Potter syndrome, hypoplastic lungs, and severe hypotension. Treatment with fresh frozen plasma and peritoneal dialysis resulted in clinical improvement and she had spontaneous urination at day 29. Endocrine studies showed a discrepancy between low plasma renin activity and high active renin concentrations, suggesting a negative feedback loop response in the renin-angiotensin system. At age 18 months, she had no obvious motor or mental retardation. An older brother with similar features had died a few days after birth. - Renal Tubular Dysgenesis with Choanal Atresia and Athelia Hisama et al. (1998) reported a lethal syndrome in 3 brothers which was characterized particularly by renal tubular dysgenesis and absent nipples (athelia). All 3 infants died neonatally and each had other malformations including preauricular pits and a preauricular tag, branchial clefts, choanal atresia, pulmonary lobation anomaly, ventricular septal defect, type IIB interrupted aortic arch, absent gallbladder, absent thymus, parathyroid gland, accessory spleen, imperforate anus, clinodactyly, and broad digits and small nails. One had a marker chromosome which appeared to be mainly Y heterochromatin and was probably unrelated to the syndrome because it was absent in the other 2 patients. X-linked recessive inheritance was possible; however, there were 4 healthy maternal uncles. Autosomal dominant inheritance with gonadal mosaicism also could not be excluded. Furthermore, a subtle chromosomal abnormality leading to contiguous gene effects could not be ruled out. Horvath and Armstrong (2007) described a female infant, born to a nonconsanguineous couple who had 2 previous miscarriages, who appeared to share a syndrome with the 3 brothers reported by Hisama et al. (1998). Her renal function was initially impaired, but improved over the first weeks of life, although there was persistent renal magnesium wasting. Her craniofacial appearance with infraorbital creases and low-set, dysplastic ears was similar to that described by Hisama et al. (1998); she also had choanal atresia, gingival cysts, a preauricular pit, athelia, right aortic arch with a vascular ring, broad digits with small nails, impaired glucose homeostasis, hypoadrenalism, neurologic impairment, and brain calcifications and periventricular leukomalacia on CT scan. She died at 13 weeks due to progressive central respiratory failure. There was a family history of neck cysts, renal failure, and adult-onset nasal passage problems. Horvath and Armstrong (2007) considered the 4 salient features of this apparent syndrome to be choanal atresia/stenosis, athelia, renal tubular dysfunction, and family and/or personal history of neck cysts or branchial clefts.
Gribouval et al. (2005) studied 11 individuals with renal tubular dysgenesis (RTD) belonging to 9 families and found that they had homozygous or compound heterozygous mutations in the genes encoding renin (REN; 179820.0002), angiotensinogen (AGT; 106150.0003), angiotensin-converting enzyme ... Gribouval et al. (2005) studied 11 individuals with renal tubular dysgenesis (RTD) belonging to 9 families and found that they had homozygous or compound heterozygous mutations in the genes encoding renin (REN; 179820.0002), angiotensinogen (AGT; 106150.0003), angiotensin-converting enzyme (ACE; 106180.0003), or angiotensin II receptor type 1 (AGTR1; 106165.0003). They proposed that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This appeared to be the first identification of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development. Hypoperfusion of the fetal kidneys had been suggested as the mechanism of RTD by findings in the twin-twin transfusion syndrome in monochorionic twin gestations (in which the donor fetus may develop RTD), major cardiac malformations, and severe liver diseases. RTD with large fontanels has also been observed in fetuses exposed in utero to ACE inhibitors or angiotensin II receptor antagonists. Severe fetal hypotension may also account for hypocalvaria, another feature of RTD of both the primary and secondary types. In contrast with endochondral bones, unaffected in RTD, persistent low blood pressure may affect skull membrane bone, which is highly vascular and requires high oxygen tension for normal growth and ossification (Barr and Cohen, 1991). Wide fontanels were described in several of the cases of renal tubular dysgenesis studied by Gribouval et al. (2005). In a Japanese infant with renal tubular dysgenesis, Uematsu et al. (2006) identified compound heterozygosity for 2 mutations in the AGT gene (106150.0004 and 106150.0005). Gribouval et al. (2012) reviewed 54 distinct mutations identified in 48 unrelated families with renal tubular dysgenesis, some of whom had previously been reported. Mutations in the ACE gene were the most common, found in 64.4% of families. Mutations in the REN gene were found in 20% of families, whereas AGT mutations were found in only 4 families, and AGTR1 mutations in 3 (8.3%). There were no genotype/phenotype correlations. The findings indicated that the disorder is due to defects affecting the common RAS pathway, regardless of the specific gene involved. Inactivation of the RAS pathway results in low systemic blood pressure and renal blood flow during fetal life, precluding normal development of the renal tubules.