[Translated article] Congenital and Hereditary Nail Disease.

Nail disorders in newborns can show independently or as components of systemic illnesses or genodermatoses. The examination of these abnormalities is complex and sometimes challenging. However, familiarity with these disorders can significantly contribute to uncovering potential underlying conditions. This review includes the physiological nail changes seen within the first few months of life, such as Beau's lines, onychoschizia, koilonychia, congenital nail fold hypertrophy of the first digit, and onychocryptosis. This review also focuses on the most relevant congenital disorders reported and how to perform differential diagnosis. Finally, this review highlights those hereditary diseases in which nail involvement is crucial for diagnosis, such as nail-patella syndrome, congenital pachyonychia, or congenital dyskeratosis, among others.

Low-grade dysplasia in Barrett's esophagus: A problematic diagnosis.

Although low-grade dysplasia (LGD) in Barrett's esophagus (BE) is a histopathological diagnosis based on different histological abnormalities, it is still problematic for different reasons. Patients without confirmed diagnosis of LGD undergo unnecessary and intensified follow-up where the risk of progression is low in the majority of cases. In contrast, the presence of confirmed LGD indicates a high risk of progression. In this article we try to address these reasons focusing on re-confirmation of LGD diagnosis, interobserver agreement, and persistent confirmed LGD. The progression risk of LGD to high-grade dysplasia and esophageal adenocarcinoma will also be reviewed.

Image-enhanced endoscopy in the diagnosis of gastric premalignant conditions and gastric cancer. / Técnicas de imagen avanzada en la detección y caracterización de las lesiones precursoras del cáncer gástrico y del cáncer gástrico precoz.

Diagnosis of early gastric cancer and its precancerous lesions remains a challenge for great part of western endoscopists. Changes seen in the mucosal pattern are generally subtle and hence difficult to identify. In this article, we will review the usefulness of conventional and virtual chromoendoscopy and magnification endoscopy in the recognition and classification of these lesions.

Recommendations of the Spanish Working Group on Crohn's disease and Ulcerative Colitis (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa - GETECCU) on dysplasia screening in inflammatory bowel disease patients. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre cribado de displasia en pacientes con enfermedad inflamatoria intestinal.

Colonic inflammatory bowel diseases have a higher risk of developing colorectal cancer compared to the general population, which is why they require endoscopic screening techniques with specific follow-up intervals based on the different risk factors described on the literature. This position paper analyzes the current scientific evidence for the different endoscopic techniques available today, how their implementation should be carried out in endoscopic units and describes in detail how their implementation should be carried out, in which patients and with what interval, and finally, what should be the response to finding dysplasia, proposing a specific follow-up algorithm.

Quality in diagnostic upper gastrointestinal endoscopy for the detection and surveillance of gastric cancer precursor lesions: Position paper of AEG, SEED and SEAP. / Documento de posicionamiento de la AEG, la SEED y la SEAP sobre calidad de la endoscopia digestiva alta para la detección y vigilancia de las lesiones precursoras de cáncer gástrico.

This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] and the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of gastric cancer precursor lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice.

Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP. / Documento de posicionamiento de la AEG, la SEED y la SEAP sobre cribado de cáncer gástrico en poblaciones con baja incidencia.

This positioning document, sponsored by the Asociación Española de Gastroenterología, the Sociedad Española de Endoscopia Digestiva and the Sociedad Española de Anatomía Patológica, aims to establish recommendations for the screening of gastric cancer (GC) in low incidence populations, such as the Spanish. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates screening in the general population, individuals with relatives with GC and subjects with GC precursor lesions (GCPL). The goal of the interventions should be to reduce GC related mortality. We recommend the use of the OLGIM classification and determine the intestinal metaplasia (IM) subtype in the evaluation of GCPL. We do not recommend to establish endoscopic mass screening for GC or Helicobacter pylori. However, the document strongly recommends to treat H.pylori if the infection is detected, and the investigation and treatment in individuals with a family history of GC or with GCPL. Instead, we recommend against the use of serological tests to detect GCPL. Endoscopic screening is suggested only in individuals that meet familial GC criteria. As for individuals with GCPL, endoscopic surveillance is only suggested in extensive IM associated with additional risk factors (incomplete IM and/or a family history of GC), after resection of dysplastic lesions or in patients with dysplasia without visible lesion after a high quality gastroscopy with chromoendoscopy.

Spontaneous coronary artery dissection. / Disección coronaria espontánea.

Spontaneous coronary artery dissection is an underdiagnosed entity. It has been recognized as an important cause of acute coronary syndrome and sudden death, particularly among young women and individuals with few conventional atherosclerotic risk factors. This document provides an exhaustive review of the pathophysiology and etiology of this disease. In addition, we describe the main clinical characteristics of these patients, the diagnostic tests that must be performed, and the most appropriate treatment.

Inner ear malformations: a practical diagnostic approach. / Malformaciones del oído interno: una aproximación diagnóstica práctica.

Pediatric sensorineural hearing loss is a major cause of disability; although inner ear malformations account for only 20-40% of all cases, recognition and characterization will be vital for the proper management of these patients. In this article relevant anatomy and development of inner ear are surveyed. The role of neuroimaging in pediatric sensorineural hearing loss and cochlear preimplantation study are assessed. The need for a universal system of classification of inner ear malformations with therapeutic and prognostic implications is highlighted. And finally, the radiological findings of each type of malformation are concisely described and depicted. Computed tomography and magnetic resonance imaging play a crucial role in the characterization of inner ear malformations and allow the assessment of the anatomical structures that enable the selection of appropriate treatment and surgical approach.

[Usefulness of systematic chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions]. / Utilidad de la endoscopia sistemática con bicromoendoscopia para la detección de displasia en pacientes con lesiones premalignas gástricas.

INTRODUCTION: Premalignant gastric lesions have an increased risk to develop gastric cancer. OBJECTIVE: To evaluate the usefulness of systematic endoscopy that includes chromoendoscopy with a double dye staining technique for the detection of dysplasia in patients with premalignant gastric lesions. PATIENTS AND METHODS: This longitudinal, prospective study was performed in patients with gastric atrophy, intestinal metaplasia or dysplasia who were referred for endoscopy less than 6 months after the initial diagnosis. The second endoscopy was performed in three phases: phase 1, exhaustive and systematic review of the mucosa with photographic documentation and biopsies of suspicious areas; phase 2, chromoendoscopy with a double dye staining technique using acetic acid 1.2% and indigo carmine 0.5%; phase 3, topographic mapping and random biopsies. RESULTS: A total of 50 patients were included. Nine (18%) had atrophic gastritis, 38 (76%) had intestinal metaplasia, and 3 (6%) had low-grade dysplasia. Systematic endoscopy with chromoendoscopy using a double dye staining technique detected more patients with dysplasia (9 versus 3, p<.05), and a larger number of biopsies with the diagnosis of dysplasia were obtained. This occurred for visible (6 vs. 0, p<.05) and non-visible lesions (6 vs. 3, p=NS). In one patient, initial low-grade dysplasia was not detected again in the systematic endoscopy, giving a global endoscopic performance for the detection of lesions of 92%. CONCLUSIONS: Patients with premalignant gastric lesions have synchronous lesions with greater histological severity, which are detected when systematic endoscopy is conducted with indigo carmine dye added to acetic acid.

[Prevalence of altered mismatch repair protein nuclear expression detected by immunohistochemistry on adenomas with high-grade dysplasia and features associated with this risk in a population-based study]. / Prevalencia de alteración de expresión nuclear de proteínas reparadoras con inmunohistoquímica sobre adenomas con displasia de alto grado y características asociadas a dicho riesgo en un estudio de base poblacional.

INTRODUCTION: Alteration of mismatch repair system protein expression detected by immunohistochemistry (IHQ) in tumoural tissue is a useful technique for Lynch Syndrome (LS) screening. A recent review proposes LS screening through immunohistochemical study not only in all diagnosed cases of colorectal cancer (CRC) but also in advanced adenomas, especially in young patients. OBJECTIVE: To assess the prevalence of altered IHQ carried out in all adenomas with high-grade dysplasia (HGD) diagnosed in our community in 2011, as well as the variables associated with this alteration. METHODS: We included all the cases of adenomatous polyps with HGD diagnosed in the three public pathology laboratories of Navarre during 2011 and performed a statistical study to assess the association between different patient and lesion characteristics and altered IHQ results. RESULTS: A total of 213 colonic adenomas with HGD were diagnosed, and 26 (12.2%) cases were excluded from the final analysis (2 known LS, 22 without IHQ study and 2 with inconclusive IHQ studies). The final number of adenomas included was 187. Pathologic results were found in 10 cases (5.35%)-6 cases in MLH1 and PMS2, 2 cases in PMS2, 1 case in MSH6 and 1 case in MSH2 and MSH6. The factors showing a statistically significant association with the presence of abnormal proteins were the synchronous presence of CRC, the presence of only one advanced adenoma, proximal location of HGD and age <50 years. CONCLUSIONS: The percentage of pathologic nuclear expression found in IHQ is high. Consequently, screening of all diagnosed HGD could be indicated, especially in young patients, with a single AA and proximal HGD.

Low-dose computed tomography to diagnose fetal bone dysplasias. / Tomografía computarizada fetal de baja dosis para diagnosticar displasias óseas.

We present a case of cleidocranial dysplasia diagnosed by low-dose fetal computed tomography (CT) in the 25th week of gestation. Severe bone dysplasia was suspected because of the fetus' low percentile in long bones length and the appearance of craniosynostosis on sonography. CT found no abnormalities incompatible with life. The effective dose was 5 mSv, within the recommended range for this type of examination. Low-dose fetal CT is a new technique that makes precision study of the bony structures possible from the second trimester of pregnancy. In Spain, abortion is legal even after the 22nd week of gestation in cases of severe fetal malformations. Therefore, in cases in which severe bone dysplasia is suspected, radiologists must know the strategies for reducing the dose of radiation while maintaining sufficient diagnostic quality, and they must also know which bony structures to evaluate.

Corpora amylacea in the neocortex in patients with temporal lobe epilepsy and focal cortical dysplasia.

INTRODUCTION: Corpora amylacea (CoA) are present in about 60% of atrophic hippocampi resected from patients with drug resistant temporal lobe epilepsy (DRTLE). They have also been described in the lateral temporal neocortex, although less frequently. OBJECTIVE: The objective is to measure the presence, distribution and density of CoA in the lateral temporal lobes of patients with DRTLE and focal cortical dysplasia (FCD), also examining how CoA density may be linked to demographic and clinical traits. METHODS: Resected tissue from 35 patients was analysed. CoA density was assessed with a semi-quantitative scale according to the criteria established by Cherian et al. RESULTS: Presence of CoA in the neocortex of 9 patients was associated with hippocampal sclerosis (FCD type iiia, 7 cases), disembryoplastic neuroepithelial tumour (FCD type iiib, 1 case), and cavernous angioma (FCD type iiic, 1 case). The meningeal surface (MS) was involved in all cases, and 8 cases displayed CoA in the cerebral parenchyma (white matter) and around blood vessels. CoA density on the MS showed a negative correlation with age at seizure onset (r = -0.828, P<.05) and a positive correlation with disease duration (r = 0.678, P<.05) but not with postoperative clinical outcome. CONCLUSIONS: Patients with DRTLE and a primary lesion (hippocampal sclerosis, tumour, vascular malformation) associated with mild FCD were shown to have CoA deposits in the neocortex. No association was found between presence of CoA and clinical outcome one year after surgery.

Cervical intraepithelial neoplasia grade 2 or worse in Galicia, Spain: HPV 16 prevalence and vaccination impact.

INTRODUCTION: The etiology of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) can influence the efficacy of Public Health preventive strategies. This study aimed to determine the high-risk papillomavirus (HR-HPV) prevalence in CIN2+ cases in unvaccinated women in Galicia (Spain), the expected impact of bivalent vaccination, and the distribution of HPV 16 in squamous lesions. MATERIAL AND METHODS: Ninety-four histologically confirmed cases of CIN2+ (2009-2010) were retrospectively studied: 23 CIN2, 58 CIN3- squamous carcinoma in situ (CIN3-CIS), 5 adenocarcinoma in situ (AIS), and 8 invasive squamous cervical cancer (SCC). Linear Array HPV Genotyping Test (Roche Diagnostics, Mannheim, Germany) was performed on the cervical specimens. Bivalent vaccination impact was calculated, based on regional vaccination coverage data, local HR-HPV prevalence, and reported efficacy (direct and cross-protection) of the vaccine. RESULTS: HR-HPV prevalence was 96.8%. The most frequent genotypes were HPV 16 (48.8-58.2%) and HPV 31 (9.3%-12.1%), considering single infections or single-multiple infections, respectively (hierarchical attribution). In squamous lesions, HPV 16 prevalence in women younger than 45 years of age increased in severe lesions (CIN3-CIS/SCC, OR 4.2), and was higher than in older women (OR 5.5). The vaccine could reduce the cumulative incidence of CIN2+ by 50.6% (direct protection), or by 62.7% (direct and cross-protection). CONCLUSION: HPV vaccination could have a great impact in women younger than 45 years of age due to the high prevalence of HPV 16 in their lesions.

[Total hip arthroplasty with supracondylar shortening osteotomy in Crowe 4 inveterate hip dislocation: case report and surgical technique]. / Artroplastía total de cadera con osteotomía de acortamiento supracondílea en luxación inveterada de cadera Crowe 4: caso clínico y técnica quirúrgica.

Structural deformities of the acetabulum secondary to developmental dysplasia of the hip (DDH) are one of the most common causes requiring total hip arthroplasty (THA), whether in conjunction with femoral osteotomy in cases of Crowe dislocation 4. Several techniques have been described, studied, and compared, but there is no superiority of one technique over another. Currently, most hip surgeons perform a subtrochanteric osteotomy. With a follow-up of 10 years, good results have been obtained, so there is a need to present a therapeutic alternative with potential benefits, mainly in restoring the center of rotation of the hip, preserving the proximal bone component, and reducing complications. Therefore, this study aims to describe the surgical technique of CTA in conjunction with supracondylar shortening osteotomy in a 29-year-old female patient, using an uncemented acetabular cup, a short uncemented stem with ceramic-polyethylene bearing, and distal fixation with a 4-hole plate LC-LCP, with the goal of restoring the natural biomechanics of the hip.

Las deformidades estructurales del acetábulo como secuelas de displasia en el desarrollo de la cadera es una de las patologías más frecuentes que ameritan como tratamiento la cirugía de artroplastía total de cadera (ATC) asociada o no a osteotomía femoral en casos de luxación inveterada clasificada como Crowe 4. Múltiples técnicas han sido descritas, estudiadas y comparadas; sin embargo, no existe superioridad de una sobre otra. Actualmente, la osteotomía realizada por la mayoría de los cirujanos de cadera es subtrocantérica, se han reportado buenos resultados a 10 años de seguimiento. La necesidad de presentar una alternativa terapéutica con posibles beneficios, principalmente en la restitución del centro de rotación de la cadera, preservación de componente óseo proximal y disminución de las complicaciones, es meritoria en el campo quirúrgico. Por lo tanto, este estudio se propone describir la técnica quirúrgica de ATC asociada a osteotomía de acortamiento supracondílea en un paciente femenino de 29 años, con uso de copa acetabular no cementada, vástago corto no cementado con par de fricción cerámica-polietileno y fijación distal con placa LC-LCP de cuatro orificios, con el objetivo de restaurar la biomecánica natural de la cadera.

Gel immersion endoscopic mucosal resection for early gastric neoplasms: a multicenter case series study.

Several cases have been reported that suggest the efficacy of gel immersion endoscopic mucosal resection (GI-EMR) for gastric neoplasms. However, no study has evaluated treatment outcomes of GI-EMR for gastric neoplasms. This study aimed to investigate the efficacy and safety of GI-EMR for early gastric neoplasms. Nine patients (17 lesions) undergoing gastric GI-EMR were included, with a median lesion size of 10 mm (interquartile range [IQR] 5-13 mm). All lesions were protruding or flat elevated. The median procedure time was 3 minutes (IQR 2-5) and en bloc resection was achieved in all cases. Among 15 neoplastic lesions, the R0 resection rate was 86.7% (13/15 lesions). Adverse events included immediate bleeding requiring hemostasis in two cases, which was controlled endoscopically. No delayed bleeding or perforation occurred. In conclusion, GI-EMR may be a safe and effective treatment for early, small gastric neoplasms. However, due to the small sample in the present study, further investigation is required regarding the indication for this technique.

The white ring sign is useful for differentiating between fundic gland polyps and gastric adenocarcinoma of the fundic gland type.

Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.

Endoscopic scoring indices for assessing disease severity in familial adenomatous polyposis: Systematic review.

Background and study aims There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating properties of existing endoscopic severity indices for FAP. Methods We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2023 to identify randomized controlled trials (RCTs) that utilized endoscopic outcomes or studies that evaluated the operating properties of endoscopic disease severity indices in FAP. Results A total of 134 studies were included. We evaluated scoring indices and component items of scoring indices, such as polyp count, polyp size, and histology. Partial validation was observed for polyp count and size. The most commonly reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal involvement. A single study reported almost perfect interobserver and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden, has been partially validated. It showed substantial interobserver reliability; however, the intra-observer reliability was not assessed. Novel criteria for high-risk gastric polyps have been developed and assessed for interobserver reliability. However, these criteria showed a poor level of agreement. Other scoring indices assessing the anal transition zone, duodenal, and colorectal polyps have not undergone validation. Conclusions There are no fully validated endoscopic disease severity indices for FAP. Development and validation of a reliable and responsive endoscopic disease severity instrument will be informative for clinical care and RCTs of pharmacological therapies for FAP.

[Prevalence and sequence of metaplasia-dysplasia-carcinoma of the gallbladder. A single centre retrospective study]. / Prevalencia y secuencia metaplasia-displasia-carcinoma de vesícula biliar. Estudio retrospectivo unicéntrico.

INTRODUCTION: We report the frequency and age of metaplasia, dysplasia and carcinoma of the gallbladder, and seek to establish a sequence of progression of these, since several studies suggest that this is the carcinogenesis pathway. MATERIAL AND METHODS: Descriptive retrospective cross-sectional study over a period of 4 years, with an analytical component of 1,514 patients with cholelithiasis, in whom cholecystectomy were performed. RESULTS: The mean age of the sample was 46 years and 72% of patients were female. The prevalence (and mean age) of pyloric metaplasia, intestinal metaplasia, dysplasia and carcinoma was 22.6 (47), 2.1 (46), 0.2 (54) and 0.6% (63 years), respectively. There was a significant association between intestinal and pyloric metaplasia (P<.001, chi(2)) and between dysplasia and carcinoma (P<.005, Yates), but not between metaplasia and dysplasia. CONCLUSION: Improved studies should be conducted for the correct interpretation of the pathogenesis of gallbladder cancer.

Bone abnormalities in the middle Anisian marine sauropsids from Winterswijk.

While the occurrence of skeletal pathologies in Middle Triassic marine reptiles has been poorly documented until now, massive accumulations of bone remains from the Germanic Basin provide the opportunities for documentation. Herein, we describe skeletal abnormalities in the Middle Triassic bone material from the Vossenveld Formation of Winterswijk, the Netherlands. The aim of the study is to distinguish in the studied bones pathologies resulting from malady or trauma and taphonomic alterations. Furthermore, an attempt was made to assess on how the pathologies also represent paleoecological data. Our survey led to the identification of one broken and healed bone, one case of abnormal coossification, and one case of posttraumatic fibro-osseous dysplasia. While the latter two pathologies give little insight into the ecology and function of the affected animals, the fractured dentary is attributed to Nothosaurus marchicus, a common sauropterygian macropredator. It proves that the individual survived long enough to heal, despite the injury hampering its hunting potential. One abnormally shaped humerus is interpreted as postmortem taphonomic deformation, emphasizing the necessity of utilization of detailed diagnostics to distinguish actual paleopathologies from nonbiological distortion.

[The enigma of Henry IV's disease: Did he suffer from McCune-Albright syndrome/fibrous dysplasia?] / El enigma de la enfermedad de Enrique IV, rey de Castilla: ¿padeció síndrome de McCune-Albright/displasia fibrosa?

BACKGROUND: Henry IV King of Castile, last king of the Trastámara dynasty, was the brother of Isabella the Catholic. He is known as "the impotent". Based on previous descriptions by historians and biographers, Gregorio Marañón in 1922 described him as "eunuchoid dysplastic with acromegalic reaction and clear schizoid features". METHODS: In 1946, a post-mortem inspection was carried out on the mummified corpse found in the Monastery of Guadalupe. A written document and some photographs were recorded. We have collected the signs and symptoms described and applied the international classification of diseases recommended by the World Health Organisation, ICD11-2023. We have relied on the coins issued in the money of Henry IV, on which we have identified enlargement of the thyroid gland. RESULTS: With the data available at this time, we suggest that Henry IV most probably suffered from: facial and polyostotic bone dysplasia, kyphosis, limb limping, multiple endocrine disorders, acromegaly with macrognatia, nodular thyroid disease, malodorous diaphoresis, erectile dysfunction, hypospadias, abnormal sexual development, "feminoid pelvis", abdominal colic, oligodontia and dental displacement. It is possible that he also suffered from: precocious puberty, renal lithiasis with debilitating phosphaturia, carpal tunnel, thrombopenia and growth hormone-producing pituitary hyperplasia or adenoma. CONCLUSION: We suggest that Henry IV may have suffered from McCune-Albrigth syndrome associated with fibrous dysplasia, a rare disease due to gain-of-function mutations in the GNAS gene.