Traqueobroncopatía osteocondroplástica: reporte de cuatro casos clínicos / Osteochondroplastic tracheobronchopathy: four case reports

INTRODUCCIÓN: La traqueobroncopatía osteocondroplástica es una rara enfermedad crónica benigna de etiología desconocida. La broncoscopía sigue siendo el estándar de oro para el reconocimiento de traqueopatía osteocondroplástica. Sus hallazgos típicos se describen como un empedrado, un jardín de rocas, una apariencia de paisaje montañoso o de una cueva con estalactitas. El objetivo del presente trabajo es mostrar las principales características clínicas de una patología poco conocida. CASOS CLÍNICOS: Se analizaron los datos clínicos de cuatro pacientes de mediana edad, tres fueron hombres y una mujer. Los principales síntomas clínicos fueron tos crónica, disnea, disfonía. Los pacientes tuvieron un diagnóstico preliminar mediante tomografía axial computarizada de tórax, confirmado por examen video broncoscópico e histopatológico. El tratamiento incluyó medicamentos para los síntomas y en un solo caso criocirugía y coagulación con argón plasma. DISCUSIÓN: El diagnóstico de traqueobroncopatía osteocondroplástica no fue sencillo por ser una entidad rara, cuyos síntomas son inespecíficos y muy frecuentes en otras patologías. En Perú no se han publicado artículos de serie de casos sobre esta patología. Por lo tanto, tomamos como referencia artículos originales publicados en otros países para compararlos con nuestros hallazgos. CONCLUSIÓN: La traqueopatía osteocondroplástica es una enfermedad benigna que predispone a los adultos, los hombres tienen más probabilidades de verse afectados. Sus manifestaciones clínicas son inespecíficas; frecuentemente de origen faríngeo y la causa no está aún definida. La tomografía axial computarizada de tórax combinada con video broncoscopía son los principales procedimientos para el diagnóstico. No existe un estándar de tratamiento con efectos terapéuticos consistentes.

INTRODUCTION: Osteochondroplastic tracheobronchopathy is a rare benign chronic disease of unknown etiology. Bronchoscopy remains the gold standard for diagnosing osteochondroplastic tracheobronchopathy. Its typical findings are described as a cobblestone, rock garden, mountainscape, or stalactite cave appearance. The present work aims to show the main clinical features of this rare pathology. CLINICAL CASES: The clinical data of four middle-aged patients, three men and one woman, were analyzed. The main clinical symptoms were chronic cough, dyspnea, and dysphonia. The patient's preliminary diagnosis was made by computed axial tomography of the chest, confirmed by bronchoscopy and histopathological examination. Treatment included medication for symptoms and, in one case, cryosurgery and argon plasma coagulation. DISCUSSION: Diagnosing osteochondroplastic tracheobronchopathy was not easy, given its uncommon nature and non-specific symptoms often found in other pathologies. No case series articles on this pathology have been published in Peru. Therefore, we used the original articles published in other countries to reference our findings. CONCLUSION: Osteochondroplastic tracheopathy is a benign disease that typically affects adults. Men are more likely to be affected. Its clinical manifestations are non-specific and frequently of pharyngeal origin, and the cause is not yet defined. Chest computed axial tomography combined with bronchoscopy are the main diagnostic procedures. There is no standard treatment with consistent therapeutic effects.

Acondroplasia severa con retraso del desarrollo y acantosis nigricans (SADDAN) / Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN)

RESUMEN La acondroplasia severa con retraso del desarrollo y acantosis nigricans (SADDAN) es una rara y letal displasia esquelética. Presentamos el primer caso detectado en Perú, en un infante de 13 meses con características fenotípicas de macrocefalia relativa, tórax estrecho, extremidades micromélicas y piel en acordeón; asimismo, un marcado retraso del desarrollo psicomotor en todos los hitos (prueba peruana) y acantosis nigricans. El paciente tuvo mala evolución clínica caracterizada por crisis convulsivas recurrentes, dificultad respiratoria progresiva, y falleció por insuficiencia respiratoria concomitante a neumonía. Esta entidad requiere del acceso a exámenes específicos como el panel de displasias esqueléticas, la cual no es parte de la oferta en la mayoría de los hospitales del Perú. Se requiere una mayor atención las enfermedades raras, a fin de proveer diagnósticos e información oportuna a los involucrados.

ABSTRACT Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is a rare and lethal skeletal dysplasia. We present the first case detected in Peru, in a 13-month-old infant with phenotypic characteristics of relative macrocephaly, narrow thorax, micromelic extremities and accordion skin; likewise, a marked delay in psychomotor development in all milestones (Peruvian test), and acanthosis nigricans. The patient had a poor clinical evolution characterized by recurrent seizures, progressive respiratory difficulty, dying from respiratory failure concomitant to pneumonia. This entity requires access to specific exams such as the skeletal dysplasia panel, which is not part of the offering in most hospitals in Peru. Greater attention is required for rare diseases, to provide timely diagnoses and information to those involved.

Impact of achondroplasia on Latin American patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Achondroplasia (ACH), the most common form of disproportionate short stature, is caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene. Recent advances in drug therapy for ACH have highlighted the importance of elucidating the natural history and socioeconomic burden of this condition. Recognition that there are many potential issues for the patient with ACH is the first step in planning cost-effective interventions in Latin America (LATAM), a vast geographic territory comprising countries with multicultural characteristics and wide socioeconomic differences. We conducted a systematic literature review to characterize the impact of ACH on affected individuals and on healthcare resources in LATAM countries. METHODS: Searches of the global medical literature as well as regional and local medical literature up to August 2020. Observational studies on patients with ACH from any LATAM country. Pairs of reviewers independently screened eligible articles, extracted data from included studies, and assessed their risk of bias. RESULTS: Fifty-three unique studies (28 case series and cross-sectional studies and 25 case reports) including data on 1604 patients were eligible. Of these studies, 11 had data available for meta-analysis. Both premature mortality and all-cause mortality in the pooled studies was 15% [95% Confidence Interval (CI) 1.0E-3 to 0.47; I2 = 82.9%, p = 0.0029; three studies, n = 99 patients]. Frequency of cardio-respiratory-metabolic disorders was 17% [95% CI 0.04-0.37; I2 = 90.3%, p < 0.0001; four studies, n = 230 patients]; nervous system disorders was 18% [95% CI 0.07-0.33; I2 = 84.6%, p < 0.0001; six studies, n = 262 patients]; ear, nose, throat and speech disorders was 32% [95% CI 0.18-0.48; I2 = 73.4%, p = 0.0046; five studies, n = 183 patients]; and spinal issues including stenosis, compression and associated pain was 24% [95% CI 0.07-0.47; I2 = 91.3%, p < 0.0001; five studies, n = 235 patients]. CONCLUSIONS: There is currently evidence of high clinical burden in ACH patients in LATAM countries. Establishing the impact of ACH provides the necessary foundation for planning tailored and effective public health interventions.

High-Resolution Melting Analysis for Rapid Detection of Mutations in Patients with FGFR3-Related Skeletal Dysplasias.

Background: Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are related to skeletal dysplasias (SDs): acondroplasia (ACH), hypochodroplasia (HCH) and type I (TDI) and II (TDII) tanatophoric dysplasias. This study was designed to standardize and implement a high-resolution melting (HRM) technique to identify mutations in patients with these phenotypes. Methods: Initially, FGFR3 gene segments from 84 patients were PCR amplified and subjected to Sanger sequencing. Samples from 29 patients positive for mutations were analyzed by HRM. Results: Twelve of the patients FGFR3 mutations had ACH (six g.16081 G > A, three g.16081 G > C and three g.16081 G > A + g.16002 C > T); thirteen of patients with HCH had FGFR3 mutations (eight g.17333 C > A, five g.17333 C > G and five were negative); and four patients with DTI had FGFR3 mutations (three g.13526 C > T and one g.16051G > T and two patients with DTII (presented mutation g.17852 A > G). When analyzing the four SDs altogether, an overlap of the dissociation curves was observed, making genotyping difficult. When analyzed separately, however, the HRM analysis method proved to be efficient for discriminating among the mutations for each SD type, except for those patients carrying additional polymorphism concomitant to the recurrent mutation. Conclusion: We conclude that for recurrent mutations in the FGFR3 gene, that the HRM technique can be used as a faster, reliable and less expensive genotyping routine for the diagnosis of these pathologies than Sanger sequencing.

Physical therapy treatment in a para-powerlifting and para-swimming athlete with achondroplasia. case report

ABSTRACT Introduction: Achondroplasia is an autoso-mal dominant congenital condition caused by a mutation of the fibroblast growth encoding gene, which affects endochondral ossification. It is the most common cause of disproportionate short stature, generating physical disability. In the presence of disability, adapted sport emerges as a strategy designed to generate inclusion and, thereby, improve the quality of life of disabled people. The aim was to develop a physical therapy plan that included recommendations to minimize the risk of injury and prevent loss of functionality as a consequence of sports practice. Case presentation: This is the case of a 27-year-old Colombian athlete diagnosed with achondroplasia who competes in the para-powerlifting and swimming modalities. Physiotherapeutic and physical fitness evaluations were carried out, finding obesity and postural and gait pattern alterations. The available literature does not recommend practicing these sports in this type of patient; however, a training program and recommendations were designed to preserve her functionality and improve her sports performance. The plan was put into practice and tolerated adequately by the athlete. Conclusions: Training plans that promote the maintenance of optimal physical condition in adapted sports participants allow them to continue practicing their sport without compromising their life expectancy or functionality. The analysis of the present case illustrates how physical therapists play a key role in this population to minimize the possible complications derived from training and competitions.

RESUMEN Introducción. La acondroplasia es una condición congênita causada por una mutación del gen codificador de crecimiento del fibroblasto que afecta la osificación endocondral y genera discapacidad estructural; además, es la causa más común de talla baja desproporcionada. Por su parte, el deporte adaptado es una disciplina deportiva que se ajusta al colectivo de personas con discapacidad y una estrategia diseñada para generar inclusión y mejorar la calidad de vida de sus participantes. Se presenta el caso de una paciente con acondroplasia a quien se le diseñó un plan fisioterapéutico de intervención enfocado a minimizar el riesgo de lesiones y prevenir la pérdida de funcionalidad como consecuencia de la práctica deportiva. Presentación del caso. Paciente femenina de 27 años diagnosticada con acondroplasia y practicante de levantamiento de potencia adaptado y natación paralímpica, a quien mediante valoración fisioterapéutica y de la aptitud física se le encontraron alteraciones posturales y en el patrón de marcha. Dado que por su condición de base no es recomendable que practique los deportes en los cuales compite, se le diseñó un programa de entrenamiento y recomendaciones dirigido a preservar su funcionalidad y mejorar su desempeño en la práctica deportiva. El plan fue puesto en práctica y tolerado de forma adecuada por la deportista. Conclusiones. Los planes de entrenamiento que favorezcan el mantenimiento de la condición física óptima de los participantes de deportes adaptados les permiten a estos deportistas realizar su práctica sin afectar su expectativa de vida ni su funcionalidad. El análisis del presente caso muestra cómo el fisioterapeuta desempeña un rol importante en esta población, pues los puede ayudar a disminuir las posibles complicaciones que se deriven de entrenamientos y competencias.

Pubertal growth in height, sitting height and leg length in achondroplasia.

Background: Children with achondroplasia (ACH) appear to lack a pubertal growth spurt in height.Aim To explore the growth spurt in height and its segments sitting height and leg length, in a large sample of ACH cases using growth curve modelling.Subjects and methods: Height and sitting height were measured longitudinally in ACH children, and the data were analysed using the SITAR (SuperImposition by Translation and Rotation) growth model, which estimates a mean growth curve and random effects for individuals defining differences in size, pubertal timing and intensity.Results: Out of 402 ACH children, 85 boys and 75 girls aged 7-20 years had respectively 529 and 454 measurements of height and sitting height, with leg length calculated by difference. SITAR analysis identified peaks in mean height velocity at 13.3 and 11.3 years in boys and girls, with peak velocities of 4.3 and 4.4 cm/year. Mean peak velocity for sitting height was 3.0 cm/year, but leg length showed no peak. The SITAR models explained 92% to 99% of the cross-sectional variance.Conclusion: ACH children do experience a growth spurt in puberty, but only half that of control children. The spurt is due entirely to sitting height, with no leg length spurt.

Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model.

OBJECTIVES: In general population, there are three phases in the human growth curve: infancy, childhood and puberty, with different main factors involved in their regulation and mathematical models to fit them. Achondroplasia children experience a fast decreasing growth during infancy and an "adolescent growth spurt"; however, there are no longitudinal studies that cover the analysis of the whole post-natal growth. Here we analyse the whole growth curve from infancy to adulthood applying the JPA-2 mathematical model. METHODS: Twenty-seven patients, 17 girls and 10 boys with achondroplasia, who reached adult size, were included. Height growth data was collected from birth until adulthood. Individual growth curves were estimated by fitting the JPA-2 model to each individual's height for age data. RESULTS: Height growth velocity curves show that after a period of fast decreasing growth velocity since birth, with a mean of 9.7 cm/year at 1 year old, the growth velocity is stable in late preschool years, with a mean of 4.2 cm/year. In boys, age and peak height velocity in puberty were 13.75 years and 5.08 cm/year and reach a mean adult height of 130.52 cm. In girls, the age and peak height velocity in puberty were 11.1 years and 4.32 cm/year and reach a mean adult height of 119.2 cm. CONCLUSIONS: The study of individual growth curves in achondroplasia children by the JPA-2 model shows the three periods, infancy, childhood and puberty, with a similar shape but lesser in magnitude than general population.

Skeletal dysplasias in Latin America.

Skeletal dysplasias (SD) are disturbances in growth due to defects intrinsic to the bone and/or cartilage, usually affecting multiple bones and having a progressive character. In this article, we review the state of clinical and research SD resources available in Latin America, including three specific countries (Brazil, Argentina, and Chile), that have established multidisciplinary clinics for the care of these patients. From the epidemiological point of view, the SD prevalence of 3.2 per 10,000 births from nine South American countries included in the ECLAMC network represents the most accurate estimate not just in Latin America, but worldwide. In Brazil, there are currently five groups focused on SD. The data from one of these groups including the website www.ocd.med.br, created to assist in the diagnosis of SD, are highlighted showing that telemedicine for this purpose represents a good strategy for the region. The experience of more than 30 years of the SD multidisciplinary clinic in an Argentinian Hospital is presented, evidencing a solid experience mainly in the follow-up of the most frequent SD, especially those belonging the FGFR3 group and OI. In Chile, a group with 20 years of experience presents its work with geneticists and pediatricians, focusing on diagnostic purposes and clinical management. Altogether, although SD health-care and research activities in Latin America are in their early stages, the experience in these three countries seems promising and stimulating for the region as a whole.

Growth hormone effects on childrens height with achondroplasia and hypochondroplasia: a systematic review and metanalysis

Introduction: Achondroplasia (Ach) is the most frequent cause of dwarfism. The first therapeutic strategy offered to patients with Ach was. However, GH has played un important role in Ach and Hypochondroplasia (Hch), despite short-term and long-term effects. Purpose: The aim of this systematic review and meta-analysis was to assess the efficacy of GH in the height of patients with Ach and Hch in the short and long term. Methods: 12 studies were included selected from the Pubmed database (3 Randomized Clinical trials (RCTs) and 9 prospective studies) from 1993 to 2014. Comparing high and low doses of GH. The systematic review included 9 prospective studies and the high-dose GH arm of the 3 RCTs. Inclusion criteria was focused on paediatric patients with Ach and Hch treated with GH. Demographic variables were collected including age, gender, dose, height and follow-up. The height variables included height increase and height velocity. Finally, 363 patients with Ach and 41 patients with Hcb were included. A was performed with a follow-up from one to 3 years. Results: In patients with Ach the average height velocity at one, two and three years were 2.65, 1.07 and -0.87 cm/years respectively (p<0.05). The RCTs showed a significant increase in height velocity in patients treated with high dose of GH (MD= 1.38, 95% CI: 0.68-2.07, p=0.0001, I2=0%) . Height at one year increased 0.61 cm. The RCTs did not show significant differences (MD 0.11, 95% CI: 0.17-0.39, p=0.44, I2 = 0%). Finally, patients with Hch increased height velocity 4 cm/year at the first year (p<0.05). Conclusion: GH treatment is beneficial in the shor-term height of children with Ach and Hch. GH effect on different ages and subgroups is unknown, as well as its possible long--term consequences

Height growth velocity during infancy and childhood in achondroplasia.

There is a lack of knowledge about longitudinal growth during childhood in achondroplasia. We report patterns of linear growth and height growth velocity references. The sample consisted of 84 children, 41 girls and 43 boys. Growth data was collected from birth until mid-childhood. The median (interquartile range) number of measurements per child was 13.5 (12, 15). Individual growth curves were estimated by fitting the Reed 1st model to each individual's height for age data. Height growth velocities references for age centiles were calculated by LMS method. Mean (SD) birth length was 46.14 cm (2.17) and 45.53 cm (2.16), for boys and girls respectively. Individual growth curves were analyzed. Shifts in growth channels were seen: out of 84 infants, 41 (48.8%) changed more than 1 SDS between birth to 5 years old. The numbers of infants shifting upward were similar (20/84) to the infants shifting downward (21/84). Height growth velocity curves show that after a period of fast decreasing growth velocity since birth, with a mean of 15.5 cm/year and 9.5 cm/year at 6 month and 1 year old, the growth velocity is stable in late preschool years, with a mean of 4.3 cm/year. Shifts in growth channels were seen between birth and 5 years old. Professionals who follow up them must consider this phenomenon during infancy. ACH children experienced a period of fast decreasing growth during infancy and the growth curve was similar in shape and lesser in magnitude than the general population.

Bone dysplasias in 1.6 million births in Argentina.

Currently accepted birth prevalence for osteochondrodysplasias (OCDs) is about 2 per 10,000 births. Our main goal is to estimate the prevalence of OCDs in Argentina and compare it with other surveillance systems. We examined 1,663,610 births among 160 hospitals of RENAC (Red Nacional de Anomalías Congénitas - National Network of Congenital Anomalies) between November 2009 and December 2016. Cases were detected and registered according to a pre-established protocol, ranked in three diagnostic evidence levels according to available clinical documentation, and categorized according to the 9th edition of the nosology and classification of genetic skeletal disorders. Within our dataset, the most frequent groups were Group-1 (FGFR3, chondrodysplasia) and Group-25 (Osteogenesis Imperfecta and decreased bone density). Birth prevalence per 10,000 for the main OCD types, were: Achondroplasia 0.47 (95% CI: 0.38-0.59), Thanatophoric Dysplasia 0.37 (95% CI: 0.29-0.48), and the Osteogenesis Imperfecta group 0.34 (95% CI: 0.26-0.44). For total OCD, birth prevalence was 2.20 per 10.000 births (95% CI: 1.98-2.44). RENAC prevalence of total OCDs was found to be lower than that reported by the Latin-American Study of Congenital Malformations (ECLAMC) and Utah Birth Defect Network but higher than EUROCAT. Our investigation is the first study of OCD prevalence in Argentina using data from every jurisdiction of the country.

Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia.

Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) cause achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types I and II (TDI/TDII). In this study, we performed a genetic study of 123 Brazilian patients with these phenotypes. Mutation hotspots of the FGFR3 gene were PCR amplified and sequenced. All cases had recurrent mutations related to ACH, HCH, TDI or TDII, except for 2 patients. One of them had a classical TDI phenotype but a typical ACH mutation (c.1138G>A) in combination with a novel c.1130T>C mutation predicted as being pathogenic. The presence of the second c.1130T>C mutation likely explained the more severe phenotype. Another atypical patient presented with a compound phenotype that resulted from a combination of ACH and X-linked spondyloepiphyseal dysplasia tarda (OMIM 313400). Next-generation sequencing of this patient's DNA showed double heterozygosity for a typical de novo ACH c.1138G>A mutation and a maternally inherited TRAPPC2 c.6del mutation. All mutations were confirmed by Sanger sequencing. A pilot study using high-resolution melting (HRM) technique was also performed to confirm several mutations identified through sequencing. We concluded that for recurrent FGFR3 mutations, HRM can be used as a faster, reliable, and less expensive genotyping test than Sanger sequencing.

Leg length, sitting height, and body proportions references for achondroplasia: New tools for monitoring growth.

Achondroplasia is the most common form of inherited disproportionate short stature. We report leg length, sitting height, and body proportion curves for achondroplasia. Seven centile format of sitting height, leg length, sitting height/leg length ratio, sitting height/height ratio, and head circumference/height ratio were estimated by the LMS method. The Q-test was applied to assess the goodness of fit. For comparison, centiles of sitting height and leg length were graphed using Argentine national growth references for achondroplasia and non-achondroplasia populations. The sample consisted of 342 children with achondroplasia (171 males, 171 females) aged 0-18 years. The median (interquartile range) number of measurements per child was 6 (3, 12) for sitting height and 8 (3, 13) for head circumference. Median leg length increased from 14 cm at age 1 week to 44 and 40 cm (males and females, respectively) in achondroplasia adolescents which is 3.5 cm shorter than non-achondroplasia children at age 1 week and, 38 cm shorter at adolescence. Median sitting height increased from 34 cm at birth to 86 and 81 in adolescents' boys and girls respectively, only 5 cm shorter than non-achondroplasia children. Sitting height/leg length decreased from 2.61 at birth to approximately 1.90 at adolescent. Median head circumference/height ratio decreased from 0.79 at birth to 0.46 at 18 years in both sexes. Growth of lower limbs is affected early in life and becomes more noticeable throughout childhood. The disharmonic growth between the less affected trunk and the severely affected limbs determine body disproportion in achondroplasia.

Spinal anesthesia for cesarean section in a patient with achondroplasia: case report / Anestesia espinal para cesárea segmentaria en paciente con acondroplasia: reporte de caso

Abstract Introduction: The perioperative management of achondroplastic pregnant patients that will undergo lower segment cesarean section represents a clinical challenge to the anesthesiologist. Objective: To describe the anesthetic management of a pregnant patient with achondroplasia, programed for lower segment cesarean section using single-dose regional subarachnoid anesthesia, and to review the general guidelines for anesthetic management emphasizing the role of anesthesia in these patients. Methods: Case report and subject review. Results: The case of a first pregnancy in an achondroplastic, 117-cm tall patient and 38.5 weeks of gestation, programed for lower segment cesarean section is discussed. The patient received single-dose subarachnoid regional anesthesia and adjuvant opioids, with satisfactory results. Conclusion: The ideal anesthetic technique is controversial and the decision shall be based on the individual patient characteristics. The spinal technique, as the anesthetic approach to lower segment cesarean section, was satisfactory and safe in this particular patient.

Resumen Introducción: El manejo perioperatorio de pacientes acondroplásicas embarazadas que van ser llevadas a cesárea segmentaria representa un reto clínico para el anestesiólogo. Objetivo: Describir el manejo anestésico de una paciente gestante con acondroplasia programada para cesárea segmentaria utilizando anestesia regional subaracnoidea con dosis unica y realizar una revisión acerca de las pautas generales del manejo anestésico destacando el papel de la anestesia regional en este tipo de pacientes. Métodos: Reporte de caso y revisión de tema. Resultados: Presentamos el caso de una primigestante acondroplásica de 38.5 semanas y altura de 117 cm programada para cesárea segmentaria a la que se realizó una técnica anestésica regional tipo subaracnoidea con dosis única de anestésico local más coadyuvante opioide con resultados satisfactorios. Conclusiones: La técnica anestésica ideal para emplear es controversial y debe ser decidido con base en las características individuales de cada paciente. La técnica espinal fue satisfactoria y segura en esta paciente en particular como técnica anestésica para cesárea segmentaría.

Natural history of 39 patients with Achondroplasia

OBJECTIVES: To characterize the natural history of 39 achondroplastic patients diagnosed by clinical, radiological and molecular assessments. METHODS: Observational and retrospective study of 39 patients who were attended at a public tertiary level hospital between 1995 and 2016. RESULTS: Diagnosis was made prenatally in 11 patients, at birth in 9 patients and within the first year of life in 13 patients. The most prevalent clinical findings were short stature, high forehead, trident hands, genu varum and macrocephaly. The most prevalent radiographic findings were rhizomelic shortening of the long bones and narrowing of the interpediculate distance of the caudal spine. There was motor developmental delay in 18 patients and speech delay in 16 patients. The most common clinical intercurrences were middle ear dysfunction, sleep apnea, limb pain and obesity from 2 to 9 years of age. One patient was large for the gestational age but did not develop obesity. One patient developed hydrocephalus at 10 years old. The current age of the patients varies from 15 months to 36 years. The molecular study performed by Sanger sequencing of the common heterozygous mutation 1138G>A in FGFR3 was positive in all patients. Four cases were inherited, and 35 were sporadic (paternal age from 19 to 66 years). CONCLUSIONS: The diagnoses were made early based on clinical and radiographic findings. All cases were confirmed molecularly. Despite presenting a benign course, it is necessary to establish a systematic protocol for the surveillance of these patients due to the common clinical intercurrences.

Estenosis acueductal en acondroplasia: a propósito de un caso / Aqueductal Stenosis in Achondroplasia: a Clinical Case Report

Resumen: La acondroplasia es la condición asociada a talla baja desproporcionada más frecuente, caracterizada por un crecimiento óseo anormal, que resulta en talla baja con extremidades cortas e inteligencia normal. Una de las complicaciones más habituales es la compresión medular, que puede ocurrir a cualquier nivel, siendo más frecuente en la unión cráneo cervical, generando alta morbimortalidad en los primeros años de vida, principalmente por muerte súbita. Presentamos una paciente de 1 año 10 meses con diagnóstico precoz de acondroplasia, que presentó en su evolución estenosis acueductal con compresión medular, sintomática, pesquisada en control rutinario, que requirió cirugía descompresiva con buena evolución posterior. Palabras clave: Acondroplasia, estenosis acueductal, compresión medular sintomática, hidrocefalia, craniectomía suboccip

Achondroplasia is the most frequent cause of disproportionate short stature, it is characterized by abnormal growth of long bones, rendering a short-limbed individual of normal intelligence. A serious potential complication is spinal compression, which can happen at any level but is particularly common at the craniocervical junction. It can cause important morbidity during the first few years of life, including sudden death. We present a 22-monthold patient diagnosed with achondroplasia, who developed aqueductal stenosis with symptomatic spinal cord compression, diagnosed during a routine consultation, requiring decompressive surgery with excellent results. Key words: Achondroplasia, aqueductal stenosis, symptomatic spinal cord compression, hydrocephalus, suboccipital craniectomy.

Possible Achondroplastic Dwarf Skull from Montevideo, Uruguay.

Achondroplasia (chondrodystrophia) is an autosomal dominant inherited disorder affecting approximately 1 in 26,000 live births and is the most common cause of dwarfism in humans. Disproportionate short stature and a suite of craniofacial characteristics typify achondroplasia. The literature available for differential diagnosis of the disorder relies primarily on the postcranial skeleton. In this paper, a possible case of achondroplasia is presented. The cranium presents a unique suite of cranial and craniofacial dysmorphologies. The lack of postcranial remains does not permit their use in the analysis. To make a differential diagnosis and to quantify the observed craniofacial dysmorphologies, craniometric data are compared to modern clinical literature and to craniometric data from known achondroplastic dwarfs. Thin-plate spline analysis is integrated to quantify the differences in degree and magnitude of shape change. This manuscript demonstrates an appropriate methodology for identifying achondroplasia from the cranial skeleton alone.

Homozygous N540K hypochondroplasia--first report: radiological and clinical features.

We describe a 16-month-old male with N540K homozygous mutation in the FGFR3 gene who showed a more severe phenotype than hypochondroplasia (HCH). To our knowledge, a homozygous state for this mutation causing HCH has not been reported before. The clinical and radiological characteristics of our patient represent an intermediate condition between achondroplasia and achondroplasia/hypochondroplasia compound heterozygosity. This case represents a new expression of FGFR3 spectrum and it is of considerable importance for the genetic counseling in cases where both parents are affected with HCH.

Acondroplasia: diagnóstico clínico precoce / Achondroplasia: early clinical diagnosis

A acondroplasia é uma síndrome genética que afetaa ossificação endocondral, sendo uma das causas denanismo. Acomete um recém-nascido em cada oitoa dez mil nascimentos. Embora o defeito genéticotenha caráter autossômico dominante, cerca de 85%dos casos resultam de novas mutações. Os portadoresda acondroplasia apresentam características clínicastípicas como macrocefalia, baixa estatura, membroscurtos com predomínio do segmento proximal e limitaçãoda extensão dos cotovelos. Entretanto, essascaracterísticas clínicas no período neonatal podempassar despercebidas dos pais e pediatras, uma vezque os recém-nascidos normais apresentam os membroscurtos em relação ao tronco, o que dificulta aobservação dessa desproporção. No presente estudode caso, registra-se um caso típico de acondroplasiadiagnosticado imediatamente após o nascimento.

Achondroplasia is a genetic syndrome that affects the endochondralossification, being one of the causes of dwarfism.It affects one newborn in every 8 to 10 thousandbirths. Although the genetic defect is of autosomal dominantorigin, about 85% of cases result from new mutations.The typical clinical features of achondroplasia are macrocephaly,short stature, short limbs with predominanceof the proximal segment and limitation of elbow extension.However, these clinical features may go unnoticedin the neonatal period, since newborns? limbs are shorterin relation to the trunk, making it difficult for parents andpediatricians to notice this disproportion. This case reportdescribes a typical case of achondroplasia diagnosed immediatelyafter birth.

Anestesia para cesárea en paciente con acondroplasia / Anesthesia for cesarean section in a patient with achondroplasia

Introducción: En gestantes acondroplásicas se recomienda el parto por cesárea con anestesia general; sin embargo, recientemente se ha reportado el uso de técnicas conductivas con resultados adecuados. Objetivo:Describir el manejo anestésico de una paciente con acondroplasia programada para cesárea utilizando anestesia combinada espinal-epidural. Métodos y resultados:Mostramos el caso de una primigestante acondroplásica con 110 cm de estatura y embarazo de 37 semanas, en quien se realizó cesárea con anestesia conductiva guiada por ecografía, empleando una mezcla titulada de anestésico local y opiáceo, con buenos resultados para la madre y el hijo. Conclusiones: La anestesia conductiva es una alternativa en la cesárea de pacientes con acondroplasia. Aunque no existen recomendaciones claras para orientar el acceso seguro al neuroeje ni para administrar medicamentos anestésicos a este nivel, se puede considerar el uso de la ecografía y la administración titulada de fármacos neuroaxiales (epidural, epidural-espinal y espinal continua) para mejorar la seguridad y la eficacia de la técnica en este tipo de pacientes.

Introduction:Cesarean section under general anesthesia is recommended in achondroplastic pregnant patients; however, the use of conductive techniques has been recently reported, with acceptable results. Objective: To describe the anesthesia management in an achondroplastic patient scheduled for C-section under combined spinal-epidural anesthesia. Methods and results:We present the case of a first pregnancy in a patient with achondroplasia, height 110 cm and 37 weeks of gestation. The patient underwent cesarean section under ultrasound-guided conductive anesthesia, using a titrated mixture of local anesthetic and opiate, with good results for the mother and child. Conclusions:Conductive anesthesia is an option in C-section in patients with achondroplasia. Although there are no clear recommendations to guide a safe access to the neuroaxis or to administer anesthetic agents at this level, ultrasound and the titrated administration of neuraxial drugs (epidural, epidural-spinal and continuous spinal) for improved safety and efficacy of the technique in this type of patients may be considered.