Opportunistic genetic screening increases the diagnostic yield and is medically valuable for care of patients and their relatives with hereditary cancer.

BACKGROUND: Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on MGP-NGS in patients with suspicion of hereditary cancer reveals these incidental findings (IFs). METHODS: MGP-NGS was performed in patients who fulfilled the clinical criteria to undergo genetic testing according to the Catalan Health Service guidelines. Variants were classified following the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and the Cancer Variant Interpretation Group UK guidelines. RESULTS: IFs were identified in 10 (1.22%) of the 817 patients who underwent MGP-NGS. The mean age at cancer diagnosis was 49.4±9.5 years. Three IFs (30.0%) were detected in PMS2, two (20.0%) in ATM and TP53 and one (10.0%) in MSH6, NTHL1 and VHL. Seven (70.0%) IFs were single-nucleotide substitutions, two (20.0%) were deletions and one (10.0%) was a duplication. Three (30.0) IFs were located in intronic regions, three (30.3%) were nonsense, two (20.0%) were frameshift and two (20.0%) were missense variations. Six (60.0%) IFs were classified as PVs and four (40.0%) as LPVs. CONCLUSIONS: Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops.

Case report of a gallbladder agenesis, a diagnostic challenge.

INTRODUCTION AND IMPORTANCE: Agenesis of the gallbladder is an underdiagnosed entity. It can be an asymptomatic pathology, usually diagnosed incidentally as a finding on imaging techniques or in necropsies. There are symptomatic cases presenting as biliary colic too, attributed to cholecystitis or cholangitis, leading to exploratory surgeries. CASE PRESENTATION: We present a 14-year-old boy admitted to the outpatient Pediatric Gastroenterology Department with a history of daily abdominal pain for the past 2 months. Blood and fecal tests were normal. Coeliac disease, inflammatory intestinal diseases and Helicobacter pylori infection were ruled out. An abdominal US was informed of a hypodistensed gallbladder with no other findings. A CT scan was performed, which reported of an absent gallbladder. Upon these findings, a Magnetic Resonance Cholangiopancreatography (MRCP) was carried out, confirming the diagnosis of agenesis of the gallbladder. CLINICAL DISCUSSION: Its diagnosis still poses a challenge, as an absent gallbladder may not always be apparent by US, with the MRCP being the gold-standard test for examining the biliary tract. The prognosis is usually good, and the treatment of choice consists of antispasmodics when needed. There are few cases reported in literature, for this reason, our article discusses the most important aspects of agenesis of the gallbladder in order to suspect it, request the appropriate tests and saving unnecessary surgical interventions. CONCLUSION: Gallbladder agenesis is a rare entity that can lead to unnecessary diagnostic tests and interventions. The MRCP is the gold-standard test. Despite its benign nature, symptomatic treatment might be required in order to improve the patient's quality of life.

Identification of germline pathogenic variants in DNA damage repair genes by a next-generation sequencing multigene panel in BRCAX patients.

BACKGROUND: Approximately 5-10% of breast carcinomas have been related to hereditary conditions and are attributable to pathogenic variants in the BRCA1 and BRCA2 genes, which is referred to as hereditary breast and ovarian cancer (HBOC) syndrome. The inclusion of additional genes that can be related to HBOC syndrome is under intense evaluation due to the high proportion of patients with HBOC criteria who do not present pathogenic mutations in BRCA genes, named BRCAX, despite having high clinical suspicion of hereditary cancer. The main aim is to identify new potentially pathogenic gene variants that may contribute to HBOC to improve the efficiency of routine diagnostic tests in this hereditary condition. METHODS: A retrospective cohort of 77 HBOC BRCAX patients was analyzed by next-generation sequencing using a targeted multigene panel composed of 25 genes related to hereditary cancer and deficiencies in DNA repair pathways. RESULTS: We found 9 variants in 7 different genes, which were confirmed by automated sequencing. Six variants were classified as pathogenic or likely pathogenic. Three of them were located in the PALB2 gene, one in the BRIP1 gene, one in the BARD1 gene and 1 in the RAD50 gene. In addition, three variants of uncertain significance (VUS) were detected in the TP53, CHEK2, and CDH1 genes. CONCLUSIONS: We identified that 8% of BRCAX patients were carriers of pathogenic variants in genes other than BRCA1 and BRCA2. Therefore, wide gene panels, including clinically actionable genes, should be routinely used in the screening of HBOC in our population. We observed differences from other studies in the prevalence of mutated genes, most likely due to differences in the selection criteria of the probands and in the population analyzed. The high incidence of deleterious variant detection in PALB2 supports its significant role in breast cancer susceptibility and reinforces its inclusion in the HBOC genetic diagnostic process.

Diagnóstico diferencial en el paciente con calcificaciones pancreáticas / Differential diagnosis of pancreatic calcifications

La pancreatitis crónica (PC) es una enfermedad de incidencia creciente en la población pediátrica, aunque desconocida, y conlleva una importante comorbilidad. La clínica inicial suele ser la propia de un episodio de pancreatitis aguda pero la importancia recae en el desarrollo, al cabo de meses o años, de insuficiencia pancreática. Para su diagnóstico será necesario tener un alto índice de sospecha clínica y realizar pruebas de imagen que demuestren cambios propios de la PC. El manejo de esta entidad deberá ser multidisciplinar y consistirá en controlar de forma adecuada el dolor e iniciar tratamiento sustitutivo cuando se constate la presencia de insuficiencia pancreática exocrina y endocrina. El caso que se reporta a continuación es un buen ejemplo de un caso de PC con presencia de insuficiencia exocrina y endocrina. Se documenta el proceso diagnóstico de la PC, en cuanto a pruebas de imagen y pruebas que demuestren la presencia de insuficiencia pancreática. Se exponen también las diferentes pruebas que se realizan para llegar a la etiología del cuadro. Se intenta reflejar el manejo que se debe llevar a cabo en estos pacientes y el seguimiento estricto que requieren.

Chronic pancreatitis (CP) is a disease with increasing incidence, though unknown, in the last years in the pediatric population which entails important comorbidities. The initial symptomatology is similar to the clinical scenario of acute pancreatitis, but its importance relies on the development, in months to years, of pancreatic insufficiency. For its diagnosis a high clinical suspicion and typical image findings are necessary. The management of this entity is held by a multidisciplinary team and the main goal is to assure an optimal pain control and start substitutive treatment once the pancreatic insufficiency is diagnosed. The clinical case that follows is a good example of CP with stablished pancreatic exocrine and endocrine insufficiency. It documents the diagnostic process of CP, regarding the imaging tools used and other laboratory test that manifested the pancreatic insufficiency. We expose the different etiologic tests that were performed in order to get to the etiologic diagnosis. It intends to reflect on the management needed for these patients and the strict follow-up that must be done.

Síndrome d'hiperèmesi per cannabinoides com a causa de vòmits incoercibles / Síndrome de hiperemesis por cannabinoides como causa de vómitos incoercibles / Cannabinoid hyperemesis syndrome as a cause of incoercible vomiting

INTRODUCCIÓ: La síndrome d'hiperèmesi per cannabinoides (SHC) és una entitat de prevalença creixent en pediatria a causa de l'augment del consum de cànnabis en aquesta població, particularment en l'adolescència, durant els últims anys. Per això és rellevant conèixer-la I tenir-la present en el diagnòstic diferencial davant d'una clínica compatible. OBSERVACIÓ CLÍNICA: En aquest article es presenten dos casos diagnosticats d'SHC, amb diferents formes de presentació, ja que el primer té una evolució més llarga I va acompanyat d'alteracions hidroelectrolítiques importants, mentre que el segon té una presentació més aguda, amb menys repercussió homeostàtica. Ambdós casos presenten una resolució progressiva en retirar el consum de la substància. COMENTARIS: La fisiopatologia de l'SHC és poc coneguda. Es tracta d'una reacció paradoxal del cànnabis, que a baixes dosis té activitat antiemètica però que en aquests pacients provoca l'efecte contrari. Es manifesta clínicament en forma d'episodis cíclics de vòmits I abdominàlgia que característicament milloren amb banys d'aigua calenta. En ocasions, el quadre pot ser greu I anar acompanyat de deshidratació I alcalosi importants, fet pel qual alguns pacients són sotmesos a nombroses exploracions complementàries abans d'arribar al diagnòstic d'exclusió d'SHC. L'únic tractament curatiu és l'abstinència, però sovint necessiten fluïdoteràpia o antiemètics, tot I que aquests últims són poc efectius. És fonamental el tractament multidisciplinari (pediàtric, psicològic/psiquiàtric I social) per aconseguir suprimir-ne el consum

INTRODUCCIÓN: El síndrome de hiperemesis por cannabinoides (SHC) constituye una entidad de prevalencia creciente en pediatría a causa del aumento del consumo de cannabis en esta población, particularmente en la adolescencia, durante los últimos años. Por este motivo es relevante conocerla y tenerla presente en el diagnóstico diferencial ante una clínica compatible. OBSERVACIÓN CLÍNICA: En este artículo se presentan dos casos diagnosticados de SHC con diferentes formas de presentación: el primero, de larga evolución, muestra al diagnóstico alteraciones hidroelectrolíticas importantes mientras que el segundo, de presentación más aguda, asocia menor repercusión homeostática. Ambos presentan una mejoría progresiva con resolución completa al conseguir la abstinencia. COMENTARIOS: La fisiopatología del SHC es poco conocida. Se trata de una reacción paradójica al cannabis, que a dosis bajas posee un efecto antiemético, pero que actúa en estos pacientes como emetizante. Se manifiesta clínicamente en forma de episodios cíclicos de vómitos y abdominalgia que característicamente mejoran con baños de agua caliente. En ocasiones puede ser grave, acompañándose de deshidratación y alcalosis importantes, por lo que algunos pacientes son sometidos a numerosas exploraciones complementarias para descartar otras etiologías antes de llegar al diagnóstico de exclusión de SHC. El único tratamiento curativo es la abstinencia, si bien precisan frecuentemente de fluidoterapia o de antieméticos, aunque los últimos sean poco efectivos. Resulta fundamental un abordaje multidisciplinar (pediátrico, psicológico/psiquiátrico y social) indispensable para conseguir suspender el consumo

INTRODUCTION: Cannabinoid hyperemesis syndrome (CHS), although uncommon in the field of Pediatrics, has recently experienced an increase in prevalence due to the rise in cannabinoid use among the pediatric population, particularly adolescents. It is thus important to be aware of this entity and to include it in the differential diagnosis of recurrent vomiting. CLINICAL OBSERVATION: The current article discusses two cases of CHS with different clinical presentation: the first patient consulted with important electrolyte imbalance due to its long-term evolution, while the second, with more acute presentation, showed no homeostatic disturbance. Both were hospitalized and evolved satisfactorily until complete recovery once cannabis use was discontinued. COMMENTS: While its pathophysiology is unclear, CHS seems to be a paradoxical reaction to cannabis, a drug that in low doses acts as an antiemetic but can also induce vomiting. CHS consists of bouts of cyclic vomiting and abdominal pain that characteristically improve with hot water showers or baths. Occasionally, the clinical presentation may be severe, with dehydration and metabolic alkalosis, making patients with CHS undergo many unnecessary tests before an exclusion diagnosis can be made. Abstinence constitutes the only effective treatment. Intravenous fluid therapy may be required, and antiemetic drugs are often administered with poor results. It is therefore essential to offer psychological assistance alongside medical intervention to stop substance abuse

Síndrome de Alagille asociado a atresia intestinal / Alagille syndrome associated with intestinal atresia

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