Open Journal Systems

Received: October 24^th 2014

Accepted: January 26^th 2015

ORIGINAL CONTRIBUTIONS

Dermatoglyphics differences among children with nephrotic syndrome according to steroid response

Jorge Román Corona-Rivera,^a,b Gustavo Pérez-Cortés,^c Julieta Osuna-Osuna,^a Marcela Guadalupe Garay-Cortés,^a J. Jesús Pérez-Molina,^a Santa Ramírez-Godínez,^d Christian Peña-Padilla,^a Jehú Rivera-Vargas,^a Lucina Bobadilla-Morales^a

^aServicio de Genética, División de Pediatría, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”

^bInstituto de Genética Humana “Dr. Enrique Corona-Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara

^cServicio de Nefrología, División de Pediatría, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”

^dServicio de Nefrología, Hospital de Pediatría, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social

Guadalajara, Jalisco, México

Communication with: Román Corona-Rivera

Telephone: (33) 1058 5200, extensión 33647

Email: rocorona@cucs.udg.mx

Background: Although the association between the type of idiopathic nephrotic syndrome (INS) and a peculiar pattern of fingerprints digital would suggest the presence of genetic factors related to both, this has not been previously studied. This study aimed to evaluate if there are fingerprints patterns differences between children with steroid-resistant INS (SRNS) and those with steroid-sensitive INS (SSNS).

Methods: The frequencies distribution of arches, ulnar loops, radial loops, and whorls was studied in 60 children with SRNS, and 60 children with SSNS. Bivariate analysis to detect the relationship between each fingerprint pattern with the study groups was performed by chi-square test and to evaluate its possible association, the odds ratios (OR) were calculated with 95% confidence’s intervals (95%CI).

Results: The patients with SRNS had a higher frequency of digital whorls compared with that of patients with SSNS (46.7% vs. 30.7%, p = 0.005). Additional comparisons using a “whorls excesses” definition obtained from normative data in our population (≥ 7 whorls in females or ≥ 8 in males) were associated with increased odds for SRNS (OR 2.96, 95% CI 1.15-7.61).

Conclusions: Our findings indicate that there are differences between children with SRNS and SSNS at the level of digital dermatoglyphics, but further studies are needed to confirm this association and its possible implications.

Keywords: Dermatoglyphics; Nephrotic syndrome; Steroids; Pediatrics

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Idiopathic nephrotic syndrome (INS) is a condition with multifactorial etiology common in pediatrics, clinically defined by the presence of massive proteinuria, edema, and hypoalbuminemia linked to glomerular damage.¹ The prognosis of INS directly correlates with responsiveness to steroid treatment, making it possible to classify these patients into steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS), depending on whether it is or is not responsive to treatment with this type of drugs.^1,2 Children with INS who remain sensitive to steroids are more likely to have minimal histological changes, while the spectrum of histopathological lesions in children with SRNS are variable and include: focal segmental glomerulosclerosis, mesangial proliferative glomerulonephritis, mesangiocapillary glomerulonephritis, IgA nephropathy, and other less common injuries.³ INS is a chronic, relapsing disease for most patients with SSNS, whereas a considerable proportion of children with SRNS progress to end stage renal disease requiring dialysis and / or transplantation.^3,4 There are several hypotheses about the pathophysiology of INS, but none fully explains the appearance of the disease, and they include: (a) failure of regulatory mechanisms of genes involved in the maturation and differentiation process of lymphocytes, especially of T-cells in patients with SSNS, (b) abnormalities of podocyte proteins leading to modifications of the cytoskeleton, and (c) the likely impact of changes to the epigenome of DNA in cells, subsequent to a viral infection.²

Fingerprint patterns are subtle permanent markers of the fetal environment, but are also genetically influenced.⁵ Therefore, several studies have determined the existence of various associations between different dermatoglyphic patterns and different entities that are malformative,⁶ chromosomal,⁴ monogenic,⁷ and multifactorial.^8,9 In previous unpublished work¹⁰ we compared dermatoglyphs of 56 children with INS with a control group of 112 healthy children and, although we found no clear differences between the two, we do see them among patients with INS, which could suggest the presence of genetic factors related to the presentation or severity of INS. Since the course of INS and its outcomes vary in relation to the response to steroid treatment, this study aimed to assess whether there are differences in the patterns of fingerprints among children with SRNS and those with SSNS.

Methods

A total of 120 consecutive patients with INS were examined from May 2008 to November 2013 regarding their fingerprint patterns. The study groups were mestizo Mexican children under 16 years old, diagnosed with SRNS (n = 60) or SSNS (n = 60), from the Servicio de Nefrología Pediátrica of the Hospital Civil de Guadalajara "Dr. Juan I. Menchaca" (Guadalajara, México). Patients with INS were diagnosed by a pediatric nephrologist as SRNS or SSNS based on the response to therapy with oral glucocorticoids in accordance with the definitions and criteria of the International Study of Kidney Disease in Children (1978).¹ The characteristics of the study groups are shown in Table I. All patients with SRNS had renal biopsy, whose results were: focal segmental glomerulosclerosis in 37 (61.6%), mesangial proliferative glomerulonephritis in 21 (35%), and other injuries in 2 cases (3.4%); while patients with SSNS were considered as having INS with minimal changes, even without knowledge of their renal histology, based on their response to steroids, their clinical course, and laboratory findings assessed by the pediatric nephrologist based on the International Study of Kidney Disease in Children report (1981).¹¹

The fingerprints were obtained from both hands, using the standard method of inking and printing.¹² The evaluation and classification of fingerprint patterns was done by a geneticist, unaware of their belonging to either study group. The three basic dermal patterns in the distal phalanges of each finger were analyzed according to Penrose’s nomenclature (1968):¹³ arches, loops, and curls, based on the number of triradius. The arch (single or tented) was identified as the only figure that does not have triradius. The loops have a single triradius and are classified as ulnar or radial, depending on whether they open on the radial or ulnar side of the finger. Curls or swirls typically have two triradius and we did not consider the distinction between their various subtypes (single, double, central, uneven). We used as a non-inclusion criterion the presence of congenital anomalies and/or mental retardation, also excluding patients with genetically determined forms of nephrotic syndrome, or other secondary causes. The Ethics and Research Committee of the Hospital Civil de Guadalajara approved the study protocol with registration number 821/08, and informed consent was obtained from the patients’ parents or the patients themselves, according to their perceptive capacity. Bivariate analysis was done by Chi-squared test (or Chi-squared with Yates correction) to detect differences between each fingerprint pattern in the study groups and their possible association; the odds ratio (OR) was measured and 95% confidence intervals calculated (95% CI). Statistical analysis was done using SPSS 20.0 program.

Results

The number and distribution of each of the four main types of fingerprint was determined for each finger and hand of each group independently (Tables II and III). SRNS patients had a greater number of digital curls, compared to SSNS patients (46.7% vs. 30.7%, p = 0.005, Table II). These frequencies of curls remained elevated even when the right and left hand were compared individually (Table III). However, to test the clinical significance of overexpression of digital curls in children with SRNS, additional comparisons were made using the definition of "excesses" for each fingerprint pattern (Table IV), obtained from reference values for the normal population of western Mexico,¹⁴ also considering the differences in fingerprint patterns between the sexes, as curls are more common in men than in women. Again we found that only "excess curls" showed odds ratio of association with SRNS (Table IV). In addition, although patients with SRNS had significantly fewer ulnar loops than the SSNS group (Tables II and III), the frequencies of "excesses ulnar loops" were statistically similar and their OR showed no association (Table IV). Thus, the apparent decrease in the frequency of ulnar loops in children with SRNS was interpreted relative to a genuine excess of curls. In all assessments made, the frequencies of radial arcs and loops by group and by hand (Tables II and III), and their "excesses" (Table IV) showed no difference or association between the study groups.

Discussion

Our results indicate that the frequency of curls in patients with SRNS differs significantly from those with SSNS. Patterns of dermal ridges are anatomical characteristics resulting from the formation and subsequent regression of fetal cushions between 8-12 weeks of gestation and, in particular, it is believed that the curls are formed from some large central fetal cushions.⁵ In the normal population, curls are the second most prevalent pattern, and they are more frequent in males.^12,14 We hold that the expected predominance of males affected by INS,² does not by itself explain the higher proportion of curls observed in our children with SRNS, since this finding persisted even after comparing these frequencies with our operational definition of "excess curls" by sex (Table IV), according to our local dermatoglyphic reference study made in 300 healthy males and 300 healthy females from western Mexico.¹⁴ Therefore, we interpret the excess curls in relation to the severity of INS, given that satisfactory response to steroids is widely recognized as a good prognostic factor,² and conversely, SRNS patients have a significantly higher risk of complications or progress to more advanced stages of chronic kidney disease.¹⁵ We interpret these anatomical deviations at the dermatoglyphic level as reflections of a specific phenotype of postnatal expression, and we believe that children with SRNS may have a greater number of risk alleles than those with SSNS, and this increased genetic load may have influenced the development of their dermatoglyphs and may explain the anatomical differences observed in our study, according to one of the criteria of multifactorial diseases concerning the relationship between the severity of a disease and increased risk of recurrence, a characteristic that is indicative of a higher heritability, according to the known threshold model.¹⁶

In conclusion, assuming that SRNS is a clinically heterogeneous disease with different histological variants and several genes involved in its occurrence,^2,3,15 the excess curls observed in this work can be considered an anatomical expression of these genetic determinants, due to the fact of also being present during the formation of dermatoglyphs. However, as has happened with other initial dermatoglyphic associations,¹⁷ additional studies are needed to confirm excess digital curls as a possible anatomical marker associated with SRNS in children.

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