Phenotypic expansion in KIF1A-related dominant disorders: A description of novel variants and review of published cases.

KIF1A is a molecular motor for membrane-bound cargo important to the development and survival of sensory neurons. KIF1A dysfunction has been associated with several Mendelian disorders with a spectrum of overlapping phenotypes, ranging from spastic paraplegia to intellectual disability. We present a novel pathogenic in-frame deletion in the KIF1A molecular motor domain inherited by two affected siblings from an unaffected mother with apparent germline mosaicism. We identified eight additional cases with heterozygous, pathogenic KIF1A variants ascertained from a local data lake. Our data provide evidence for the expansion of KIF1A-associated phenotypes to include hip subluxation and dystonia as well as phenotypes observed in only a single case: gelastic cataplexy, coxa valga, and double collecting system. We review the literature and suggest that KIF1A dysfunction is better understood as a single neuromuscular disorder with variable involvement of other organ systems than a set of discrete disorders converging at a single locus.

Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase.

Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of FGFR1 is ZMYM2, and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with FGFR1, and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia or very rarely, with B-lymphoblastic leukemia (B-ALL). In this study, we analyzed the clinicopathological, cytogenetic, and molecular features of 2 new patients with the t(8;22)(p11.2;q11.2)/BCR-FGFR1 who presented with B-ALL. An underlying MPN became apparent when a morphologic remission of B-ALL was achieved after chemotherapy. We subsequently reviewed the literature and identified 18 additional cases reported with B-ALL in a background MPN or with the MPN as a chronic phase. Our data suggest that the t(8;22)(p11.2;q11.2)/BCR-FGFR1 may arise from a myeloid/B progenitor cell. It is important to recognize that neoplasms carrying the t(8;22)/BCR-FGFR1, although rare, can commonly with B lymphoblastic leukemia at the initial diagnosis, which could distract one from recognizing a possible underlying 8p11 myeloproliferative syndrome.

Cytogenetic Evolution Associated With Disease Progression in Hematopoietic Neoplasms With t(8;22)(p11;q11)/BCR-FGFR1 Rearrangement.

Hematopoietic neoplasms with FGFR1 rearrangements are rare. Clinically, patients often present with a chronic myeloproliferative neoplasm with eosinophilia and an increased risk of transformation to acute leukemia. We report a patient who initially presented with B-cell acute lymphoblastic leukemia (B-ALL) with t(8;22)(p11.2;q11.2) and an additional derivative chromosome 22 [der(22)t(8;22)]. After induction chemotherapy, B-ALL blasts were eradicated; however, a chronic myeloproliferative process emerged showing persistent t(8;22) (p11.2;q11.2) but not der(22)t(8;22). Combined morphologic and fluorescence in situ hybridization revealed that both lymphoblasts and myeloid cells harbored t(8;22)(p11.2;q11.2); but only lymphoblasts carried the additional der(22)t(8;22). This case provides direct evidence to illustrate the clonal relationship of chronic phase and blast phase in myeloid neoplasms with FGFR1 rearrangement, and demonstrates that clonal cytogenetic evolution plays an important role in disease progression.

[Lynch syndrome, Muir Torre variant: 2 cases]. / Síndrome de Lynch variante Muir-Torre: a propósito de 2 casos.

Lynch syndrome (LS) is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6 or PMS2). Muir-Torre syndrome (MTS) is a phenotypic variant of LS that includes a predisposition to sebaceous glands tumors and keratoacanthomas. We report two patients with MTS, with more than one LS-related cancer, skin lesions, family history of cancer andmicrosatellite instability and immunohistochemistry analysis.

Síndrome de Lynch variante Muir-Torre: a propósito de 2 casos / Lynch syndrome, Muir Torre variant: 2 cases

El síndrome de Lynch (SL), es un síndrome genético con patrón de herencia autosómico dominante, que predispone el desarrollo de cáncer colorrectal y neoplasias extracolónicas, debido a la mutación germinal en alguno de los genes reparadores de los errores de la replicación del ADN (MLH1, MSH2, MSH6 o PMS2). El Síndrome de Muir-Torre (SMT), es una variante fenotípica del SL que predispone además a desarrollar tumores de glándulas sebáceas y queratoacantomas. Presentamos el caso de dos pacientes con SMT, con más de una neoplasia relacionada al SL, lesiones cutáneas, antecedentes familiares de cáncer y estudios de inestabilidad de microsatélites e inmunohistoquímica...

Lynch syndrome (LS) is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6 or PMS2). Muir-Torre syndrome (MTS) is a phenotypic variant of LS that includes a predisposition to sebaceous glands tumors and keratoacanthomas. We report two patients with MTS, with more than one LS-related cancer, skin lesions, family history of cancer andmicrosatellite instability and immunohistochemistry analysis...

Características clínico-epidemiológicas de los pacientes con diagnóstico confirmado por PCR de Influenza AH1N1 hospitalizados en el Instituto Nacional de Salud del Niño durante todo el año 2009 / Clinical and epidemiological characteristics of patients with confirmed diagnosis of Influenza AH1N1 PCR hospitalized at the National Institute of Child Health for all by 2009

Introducción: En la primavera del 2009, un brote de neumonía severa fue reportado en México y se aisló el nuevo virus influenza A (H1N1), ampliamente conocido como la gripe porcina. Los subtipos de A (H1N1) raramente habrían predominado desde la pandemia de 1957. Este nuevo virus se propagó rápidamente a través del hemisferio Sur incluyendo Perú, causando un amplio rango de síntomas en niños desde una infección de vías aéreas superiores hasta una neumonía severa y fatal. Objetivo: Describir las características clínicas-epidemiológicas de los pacientes con diagnóstico confirmado por PCR de influenza A H1N1 hospitalizados en el Instituto Nacional de Salud del Niño durante todo el año 2009. Así mismo identificar los síntomas y signos de mayor sensibilidad los antecedentes fisiológicos y patológicos, y determinar las complicaciones más frecuentes. Método: Es un estudio de tipo retrospectivo, serie de casos y descriptivo, no experimental, fueron revisadas 38 historias clínicas de pacientes pediátricos con diagnostico comprobado de Influenza AH1N1 hospitalizados en el INSTITUTO NACIONAL DE SALUD DEL NIÑO durante todo el año 2009. Los datos fueron recogidos en una ficha clínica de recolección donde se evalúan las variables para la realización del estudio. Se procesaron los datos usando el programa estadístico Statistical Package for the Social Sciences (SPSS 15). Resultados: En el grupo de estudio la edad promedio de hospitalización de los pacientes con fue de 44.98 meses de edad. Se contó con 19 mujeres y 19 varones El tiempo de hospitalización fue de 17.47 días. En los antecedentes patológicos, 6 de los 38 pacientes no sufrieron enfermedades previas ni presentaban cornorbllidades...

Background In the spring of 2009, an outbreak of severe pneumonia was reported in conjunction with the concurrent isolation of a novel swine-origin influenza A (H1N1) virus (S-OIVL widely known as swine flu, in Mexico. Influenza A (H1Nl) subtype viruses have rarely predominated since the 1957 pandemic. This new virus rapi91y spread throughout the Southern Hemisphere including Peru, causing a wide range' of symptoms in children, ranging from respiratory infections to severe pneumonia and death. Objective To describe the clinical and eplderniologlcal characteristics in patients with a confirmed diagnosis of AH1Nl by Influenza Viral PCR, hospitalized at "INSTITUTO NACIONAL DE SALUD DEL NIÑO" during 2009. Also, identify signs and symptoms, physiological and preexisting conditions, and determine frequent complications. Methods This is a retrospective study, descriptive and non experimental, case report 38 clinical charts were reviewed from pediatric patients with confirmed AH1N1 diagnosis, hospitalized at "INSTITUTO NACIONAL DE SALUD DEL NIÑO" in 2009. The data was processed using the Statistical Package for the Social Sciences (SPSS). Results The study group was conformed by 19 boys and 19 girls. The median age of these hospitalized patients was 44.98 months. The average hospitalization period was 17.47 days. 6 out of the 38 patients had no preexisting diseases. Regarding the clinical examination, 17 patients had Respiratory Distress, 28(73.7per cent) Fever>38 C, 32 (84.2 per cent) Cough, 18 (47.4 per cent) Rhinorrhea, 2 (5.3 per cent) Odynophagia, 2 (5.3 per cent) Myalgias, 2 (5.3 per cent) Head he, _ (23.7 per cent) Vomits, 7 (18.4 per cent) Diarrhea, 1 (2.6 per cent) Rash, 14 (36.8 per cent) Weakness.Complicatjons: 30 (78.9 per cent) Pneumonia, 7 (18.4 per cent) Sibilant Rales, 6 (15,8 per cent) died, 18 (47.4 per cent required 02, 1 (2.3 per cent) Pneumothorax, 8 (21.1 per cent) Hypoxemia, and 16 (42.1) presented other complications...