This case illustrates the potential severity of the renal anomalies in the BOR syndrome and the inadequacy of oligohydramnios and maternal serum alpha-fetoprotein as screening methods for renal agenesis.
Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WT1 gene can result in similar genital and kidney abnormalities.
In a recent report, deregulation of expression of the gene coding for the Pax-2 DNA-binding protein was shown to generate severe kidney abnormalities in transgenic mice resembling the clinical and pathological findings in congenital nephrotic syndrome, making it a candidate gene for CNF.
Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%.
Although renal-coloboma syndrome involves both ocular and renal anomalies, some patients are affected with vesico-ureteral reflux (VUR), high frequency hearing loss, central nervous system (CNS) anomalies, and/or genital anomalies, consistent with the expression of PAX2 in these tissues during development.
Although kidney agenesis or dysgenesis has been observed in mice lacking functional ret, no clinically relevant kidney abnormalities have been reported in individuals with known RET mutations and familial medullary thyroid carcinoma (FMTC).
Recently, a member of the GATA-binding family of transcription factors was shown to be involved in the human hypoparathyroidism, sensorineural deafness and renal anomalies (HDR) syndrome.
The genetic bases of most forms of uveoretinal coloboma are elusive; mutations in PAX2 are found in only a few cases of coloboma of the retina and optic nerve that occur with renal anomalies as part of the renal-coloboma syndrome (MIM#120330; #167409).
Previous phenotype studies of Lmx1b null mice revealed dorsal limb and renal anomalies similar to human NPS, which contributed to the identification of heterozygous mutations in this LIM-homeodomain protein LMX1B as the genetic defect responsible for NPS.
Mutations in the transcription factor encoding TFAP2A gene underlie branchio-oculo-facial syndrome (BOFS), a rare dominant disorder characterized by distinctive craniofacial, ocular, ectodermal and renal anomalies.
MLL2 mutation carriers significantly more often presented with short stature and renal anomalies (p = 0.026 and 0.031, respectively), and in addition, MLL2 carriers obviously showed more frequently a typical facial gestalt (17/19) compared with non-carriers (9/15), although this result was not statistically significant (p = 0.1).
MLL2 mutation carriers significantly more often presented with short stature and renal anomalies (p = 0.026 and 0.031, respectively), and in addition, MLL2 carriers obviously showed more frequently a typical facial gestalt (17/19) compared with non-carriers (9/15), although this result was not statistically significant (p = 0.1).
The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases.
The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases.