Letters to the Editor

Abstract

>The Authors' Reply: We read with interest the letter by Hochwald and Shaoul indicating a significantly lower frequency of mandibular frenulum (MF) abnormalities in their population of patients with idiopathic hypertrophic pyloric stenosis (IHPS) (1). To date, no unambiguous pathogenesis for IHPS has been demonstrated. Our findings of MF abnormalities in IHPS (2), described 4 years ago, were not intended to be means for systematic screening for the disease. The sensitivity, specificity and predictive values reported in that article were intended as a statistical discriminator between patients and controls for a new phenotypical observation, rather than a measure for population screening. In our opinion, our findings had the merit of triggering new thinking on this common disorder of infancy whose cause or causes are still unknown. To date, several possible risk factors for the condition have been suggested, including genetic causes and toxicity from macrolide use in pregnancy and early infancy (3,4,5). However, controversy still exists regarding the pathogenetic mechanisms of the condition. The main theoretical limitations of our MF observations in IHPS were the qualitative nature of our observations. While MF agenesis is obvious, the determination of MF hypoplasia is still dependent on operator skill and experience. Our team has an experience of over 5,000 MF observations not just in IHPS. To overcome this issue, we tried to design an intraoral device for measuring MF and construct a nomogram. A major limitation of these observations is the reproducibility of the traction force applied to the inferior labium which differs with operator skill and experience. Another problem is that the measurements are operator dependent. To deal with this problem, we always rely on independent observations by experienced odontostomatologists and record the findings with standard, high resolution photographs. Although this line of research has yielded valuable observations in EDS II/III (6) and true umbilical cord knots (7), we do not consider it the most appropriate IHPS screening method. We hypothesized that the most likely reason for MF abnormalities observed in our IHPS population was a hitherto unrecognized underlying extracellular matrix (ECM) abnormality. First, we noted joint hypermobility and MF abnormalities in IHPS parents (8). As ECM is known to play a major role in angiogenesis and blood vessel geometry (9,10), we tested the hypothesis that their might be an abnormality of the vascular network geometry in IHPS (11). The results of that study (12) indicate significant differences in box-counting fractal dimensions and relative Lempel-Ziv values in IHPS patients and their unaffected parents (P < 0.000001). Those findings are in agreement with the observation of an abnormal vascularity in the pyloric canal of IHPS patients (13). In addition, as an impaired structure of ECM may affect its optical properties, we studied oral mucosal spectrophotometry in IHPS. The results suggest an abnormal light reflectance value in the violet, blue, blue-green, green, yellow and orange sections of the spectrum (14). In the absence of clear photographic documentation, missing information on potential IHPS risk factors (including familial history) and absence of a matched control population together with lack of information about inter-observer variability, a correct interpretation of the results of Hochwald and Shaoul is difficult and limits the generalization of the findings. Moreover, in their letter the authors incorrectly refer to earlier criticism to our findings. The cited letter by Jenista (15) was asking for photographic images of our patients at the typical age of IHPS onset, which we provided in our reply letter (16). In fact, in her letter, Jenista was not reporting discrepancies in the frequency of MF abnormalities in IHPS. In conclusion, the difference in the proportions of MF abnormalities in IHPS reported by Hochwald and Shaoul may possibly result from a combination of two factors: 1) Possible population- and/or pathogenesis-specific differences between the two patient cohorts; 2) Lack of comparability between the two studies. Unfortunately, the lack of information regarding joint hypermobility scores, vascular network analysis and oral mucosa light reflectance in their patients prevents a correct interpretation of the described epidemiologic differences. However, the differences observed by the authors, if confirmed, can be the key in discriminating the "genetic" from the "environmental" forms of IHPS. *Claudio De Felice, MD †Stefano Parrini, DDS, PhD †Paolo Toti, MD *Giovanni Di Maggio, MD ‡Giuseppe Latini, MD *Azienda Ospedaliera Senese Siena, Italy; †University of Siena, Siena, Italy; ‡Perrino Hospital, Brindisi and the Clinical Physiology Institute; National Research Council of Italy (IFC-CNR); Lecce Section, Italy