HNF1B maturity-onset diabetes of the young (MODY) (previously named MODY5) is a syndrome due to heterozygous molecular anomalies of the hepatocyte nuclear factor (HNF)1B that may associate diabetes, morphological and functional abnormalities of the kidneys and of the pancreas, liver test anomalies, and genital tract malformations (1,2). MODY5 is due to HNF1B point mutations in half the cases, and is associated to a chromosome 17q12 deletion encompassing the HNF1B gene in the other half (3,4).
Pectus excavatum (PE) is the most frequent anterior chest wall deformity. It has been described as an isolated anomaly or as part of many genetic syndromes, including monogenic diseases and chromosome aberrations (reviewed in 5). So far, PE has not been described in the context of HNF1B anomalies.
Following the observation of a patient with typical MODY5 and PE (case 1, Table 1), we have reviewed the files of 59 adult patients (29 males, 30 females) with an HNF1B molecular anomaly (31 mutations, 28 deletions). In six patients, the presence of PE was mentioned by the referring physician (including a father and his son, cases 1 and 2), and was confirmed by two of us. No patient had a severe form with respiratory or other clinical consequences. The main characteristics of the six patients are shown in Table 1. Diabetes, present in five of six patients, was revealed by acute onset in three patients. Basal and glucagon-stimulated C-peptide concentrations were low in the five tested patients. In the sixth patient, follow-up fasting blood glucose and HbA1c were 5.7 mmol/L and 34 mmol/mol, respectively. Renal disease was present in all patients. Liver tests abnormalities were observed in five of six patients, with fluctuating increased levels of transaminases and/or γ-glutamyl transferase. Fecal elastase concentration was decreased in three of five tested patients.
In this series of MODY5 patients, the minimal prevalence of PE was 10% (8% in probands, and 21% in male patients). Since chest wall morphology was not systematically described in the files, the actual frequency could be higher. Nevertheless, the observed prevalence is by far much higher than that expected in the general population, which has been reported to be 1:400, with a male-to-female ratio of 4:1 (5).
Among the six patients with MODY5 and PE, an HNF1B point mutation was found in four patients (three probands) and an HNF1B deletion in two patients (Table 1).
These results suggest that molecular anomalies of the HNF1B gene may be involved in the development of PE, and expand the clinical spectrum of the HNF1B-associated disease. The presence of PE may strengthen the suspicion of MODY5 in some patients with uncommon forms of diabetes.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. D.D.-L. and J.T. researched data and wrote the manuscript. C.B.-C. and J.-F.S. researched data and contributed to discussion. J.T. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.