Kidney disease has not been considered a frequent complication in Down syndrome (DS) patients; a variety of urological abnormalities and glomerulopathies have been reported in this population, and some DS patients develop chronic renal failure (CRF). The aim of this study was to improve the understanding of renal disease in patients with DS, focusing on the incidence and range of kidney and urological abnormalities in a population of DS patients. A cross-sectional study was carried out in DS patients referred from a pediatric genetics unit of a tertiary care center. Medical records were reviewed. A 24-h urine specimen and a blood sample were obtained. Fractional excretion of sodium and potassium, tubular reabsorption of phosphate, urinary excretion of calcium, magnesium, uric acid, creatinine clearance and proteinuria were determined. Ultrasound was performed to evaluate the kidneys and the urinary tract. Laboratory data were reviewed for any possible renal disorder. Sixty-nine patients, aged 12 months to 24 years, were recruited. Pathological findings included three cases of voiding disturbances and a case of hypertension in a 7-year old girl. Eight patients (11.6%) had hyperuricemia without gout. Eighteen patients (24.2%) had hyperuricosuria. Urinalysis revealed three cases of mild proteinuria and two patients with microscopic hematuria. Minor radiological abnormalities were found in five patients (7.3%). Three patients (4.5%) had CRF. Renal disease in patients with DS is not as rare as previously thought, although the majority of findings are of minor relevance. According to the variety of pathologies, and in order to detect early irreversible renal injury, it seems quite reasonable to perform regular monitoring of renal function in these patients.

BackgroundSHORT syndrome is a rare autosomal dominant condition whose name is the acronym of short stature, hyperextensibility of joints, ocular depression, Rieger anomaly and teething delay (MIM 269880). Additionally, the patients usually present a low birth weight and height, lipodystrophy, delayed bone age, hernias, low body mass index and a progeroid appearance.Case presentationIn this study, we used whole-exome sequencing approaches in two patients with clinical features of SHORT syndrome. We report the finding of a novel mutation in PIK3R1 (c.1929_1933delTGGCA; p.Asp643Aspfs*8), as well as a recurrent mutation c.1945C > T (p.Arg649Trp) in this gene.ConclusionsWe found a novel frameshift mutation in PIK3R1 (c.1929_1933delTGGCA; p.Asp643Aspfs*8) which consists of a deletion right before the site of substrate recognition. As a consequence, the protein lacks the position that interacts with the phosphotyrosine residue of the substrate, resulting in the development of SHORT syndrome.

This case of intrafamilial phenotypic variation associated with a single PRPS1 mutation complicates the genotype-phenotype correlations, which makes genetic counseling of mutation carriers difficult because of the wide spectrum of severity of the associated disorders.

In 2005, we reported on a family as having Frías syndrome (OMIM: 609640), with four affected members displaying a pattern of congenital defects nearly identical to those observed in a mother and son described by Frias [Frías et al. (1975). Birth Defects Orig Artic Ser 11:30-33]. These defects included growth deficiency, facial anomalies, and hand and foot alterations. We had the opportunity to study this family again due to the birth of another affected girl, who presented with similar facial characteristics to those of her elder half-sister and the rest of affected relatives, which consisted of mild exophthalmia, bilateral palpebral ptosis, downslanting palpebral fissures, and hypertelorism. We performed array-CGH, which identified an identical interstitial deletion of chromosome 14q22.1-q22.3 in the mother and two daughters. The deletion is 4.06 Mb in length and includes the BMP4 gene, a member of the bone morphogenetic protein (BMP) family of secreted proteins. A review of the literature showed that deletions or mutations of this gene underlie congenital defects affecting brain, eye, teeth, and digit development. Although the clinical manifestations of the current family correlate with the defects observed in patients having either 14q22-q23 deletions or mutations of BMP4, they show a milder phenotype. In order to understand the clinical variability, we evaluated the already known functional characteristics of the BMP gene members. This gene family plays an important role during early embryogenesis, and the complex synergistic functions and redundancies of the BMPs led us to conclude that haploinsufficiency of BMP4 is likely to be responsible for the clinical expression of Frías syndrome.