Hypertrophic pyloric stenosis masked by kidney failure in a male infant with a contiguous gene deletion syndrome at Xp22.31 involving the steroid sulfatase gene: case report

Abstract

Background Contiguous gene deletion syndrome at Xp22.3 resulting in nullisomy in males or Turner syndrome patients typically encompasses the steroid sulfatase gene (STS) and contiguously located other genes expanding the phenotype. In large deletions, that encompass also the Kallmann syndrome 1 gene (KAL1), occasionally infantile hypertrophic pyloric stenosis (IHPS) and congenital anomalies of the kidney and urinary tract (CAKUT) have been reported. Patient presentation We report on a male newborn with family history in maternal uncle of renal abnormalities and short stature still without ichthyosiform dermatosis. The baby presented CAKUT with kidney failure and progressive vomiting. Renal bicarbonate loss masked hypochloremic and hypokalemic metabolic alkalosis classically present in IHPS and delayed its diagnosis. Antropyloric ultrasound examination and cystourethrography were diagnostic. After Fredet-Ramstedt extramucosal pyloromyotomy feeding and growing was regular and he was discharged home. Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) × 0 involving the STS gene, but not the KAL1 gene. Conclusions Aberrant cholesterol sulfate storage due to STS deletion as the underlying pathomechanism is not limited to oculocutaneous phenotypes but could also lead to co-occurrence of both IHPS and kidney abnormalities, as we report. Thus, although these two latter pathologies have a high incidence in the neonatal age, their simultaneous association in our patient is resembling not a chance but a real correlation expanding the clinical spectrum associated with Xp22.31 deletions.

Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up

“…In addition to ichthyosis, benign corneal opacities affected approximately 10–50% of males with XLI [ 8 ], and approximately 20% of males with XLI had cryptorchidism [ 2 ]. Furthermore, autism [ 9 ], intellectual disability [ 10 – 13 ], epilepsy [ 14 ], developmental delay [ 15 ], and kidney abnormalities [ 16 ] were described in male carriers of typical XLI-associated deletions (approximately 1.6 Mb). The Xp22.31 deletion is commonly classified as pathogenic according to the American College of Medical Genetics and Genomics recommendations for interpreting and reporting constitutional copy number variations (CNVs) [ 17 ], given its association with XLI.…”

Report and follow-up on two new patients with congenital mesoblastic nephroma

“…After birth, multispecialty co-management of newborn patients, which includes the integration of high-level surgical expertise with careful neonatological intensive care [ 40 – 45 ], is necessary to limit and/or prevent complications. Finally, the precise definition of the histopathological and cytogenetic-molecular profiles [ 46 – 54 ] is indispensable to plan an individualized follow-up, oriented to early detection of any possible recurrences or associated anomalies and to better quality of life for children and their families [ 55 – 57 ].…”

Report and follow-up on two new patients with Congenital Mesoblastic Nephroma

“…After birth, multispecialty co-management of newborn patients, which includes the integration of high-level surgical expertise with careful neonatological intensive care [41][42][43][44][45][46], is necessary to limit and/or prevent complications. Finally, the precise de nition of the histopathological and cytogenetic-molecular pro les [47][48][49][50][51] is indispensable to plan an individualized follow-up, oriented to early detection of any possible recurrences or associated anomalies and to improve the quality of life of these children and their families [52][53][54].…”