Horseshoe kidney and a rare TSC2 variant in two unrelated individuals with tuberous sclerosis complex

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by abnormalities involving the skin, brain, kidney (angiomyolipomas, cysts), and heart. Horseshoe kidney has not been considered to be a common renal manifestation of TSC but it has been previously reported in two patients with TSC. We report on two unrelated females with typical manifestations of TSC, horseshoe kidney, and an identical variant c.5138G>A in exon 39 (p.Arg1713His) of TSC2 gene. These cases provide evidence that horseshoe kidney is associated with TSC and add to the evidence for the pathogenicity of this variant. Furthermore, one of the patients also had a diaphragmatic hernia which has been reported twice in the medical literature in individuals with TSC. It is possible that a diaphragmatic hernia is another rare manifestation of TSC and that TSC should be included in the differential diagnosis of infants with a diaphragmatic hernia. Given that both a horseshoe kidney and a diaphragmatic hernia are findings that can be detected prenatally on an ultrasound examination, our findings may have implications for prenatal genetic counseling.

Genetic causes of congenital diaphragmatic hernia

“…One or more cases of the following autosomal dominant conditions have all been described with CDH: Kabuki syndrome with a mutation in KMT2D/MLL2 [80], Baller–Gerold/Saethre–Chötzen with a mutation in TWIST [81], Apert syndrome with craniosynostosis and an FGFR2 mutation [82], SHORT syndrome with a BMP4 mutation [83], tuberos sclerosis type 2 with a TSC2 mutation [84], Beckwith–Wiedemann syndrome with a paternally inherited der(4)t t(4;11)(q33;p14) [85], C-trigonocephaly [86], and multiple pterygium syndrome [87] without identified causes.…”

Rare familial TSC2 gene mutation associated with atypical phenotype presentation of Tuberous Sclerosis Complex

“…Our patient has a non‐truncating mutation which, according to functional assessment, has been determined to be pathogenic [Hoogeveen‐Westerveld et al, , ]. Furthermore, this mutation has been identified in about nine individuals with predominantly mild TSC manifestations, including one who is reported as “apparently healthy” (http://www.lovd.nl/TSC2) [Hoogeveen‐Westerveld et al, ; Hirfanoglu and Gupta, ; Niemi et al, ].…”

Late-presenting congenital diaphragmatic hernia in an infant with tuberous sclerosis – case report and a review of the literature

“…In the literature, there was only one case of TSC in a neonate presented as diaphragmatic hernia [12] and we can also find mention about two other cases. One it was a 7.5-year-old girl [13], who presented with a diaphragmatic hernia, multiple cardiac rhabdomyomas and a horseshoe kidney with mutation in the TSC2 gene. The second case of TSC connected with CDH was a preterm neonate, in whom diaphragmatic hernia was found during autopsy, in addition to cardiac rhabdomyomas and intestine malrotation.…”