Achondroplasia in Latin America: practical recommendations for the multidisciplinary care of pediatric patients.

BACKGROUND: Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. Additionally, patients affected with this condition have higher frequency of sleep disorders, ear infections, hearing loss and slowed development milestones. Considering these clinical features, we aimed to summarize the regional experts' recommendations for the multidisciplinary management of patients with achondroplasia in Latin America, a vast geographic territory with multicultural characteristics and with socio-economical differences of developing countries. METHODS: Latin American experts (from Argentina, Brazil, Chile and Colombia) particiáted of an Advisory Board meeting (October 2019), and had a structured discussion how patients with achondroplasia are followed in their healthcare centers and punctuated gaps and opportunities for regional improvement in the management of achondroplasia. RESULTS: Practical recommendations have been established for genetic counselling, prenatal diagnosis and planning of delivery in patients with achondroplasia. An outline of strategies was added as follow-up guidelines to specialists according to patient developmental phases, amongst them neurologic, orthopedic, otorhinolaryngologic, nutritional and anthropometric aspects, and related to development milestones. Additionally, the role of physical therapy, physical activity, phonoaudiology and other care related to the quality of life of patients and their families were discussed. Preoperative recommendations to patients with achondroplasia were also included. CONCLUSIONS: This study summarized the main expert recommendations for the health care professionals management of achondroplasia in Latin America, reinforcing that achondroplasia-associated comorbidities are not limited to orthopedic concerns.

Juvenile panhypopituitarism in a dog - what are the therapeutic challenges?

Background: Juvenile panhypopituitarism is an endocrinopathy that affects young dogs and must be differentiated from other causes of height disorders, as one could have a deficiency of one or more adenohypophysis hormones, besides growth hormone. Diagnosis consists of excluding endocrine and non-endocrine causes. Treatment requires administration of heterologous porcine growth hormone or progestins, as well as supplementing other hormones that are deficient in the circulation. The prognosis for these patients tends to be unfavorable and they have a shorter life expectancy. The present case aimed to report the therapeutic challenges in a dog diagnosed with juvenile panhypopituitarism. Case: This study presents the case of a 6-month-old crossbred Labrador/Brazilian Fila dog, not neutered, 6.7 kg of body weight (body condition score 5/9), with a growth disorder and persistence of the puppy coat, when compared to other members of the same litter. During inspection, it was possible to observe an undersized dog and soft puppy coat, besides no bone irregularities or joint tenderness was noted. The other physical examination parameters were within the normal range for the species. No changes in complete blood count and only increases in urea, cholesterol and alkaline phosphatase activity were observed. Thyroid and abdominal ultrasound (US) examination did not reveal any remarkable changes. After serum dosage of insulin-like growth factor, thyroxine, thyrostimulating hormone, and cortisol, the patient was diagnosed with juvenile panhypopituitarism and underwent therapy with medroxyprogesterone and thyroid hormone supplementation. Monitoring was instituted at intervals of 3, 6, and 12 weeks, and currently every 3 or 4 months and the IGF-1 values normalized after 6 months with. After 8 months of therapy, the patient had good body growth and bone mineralization compared to the time of diagnosis. However, skeletal development was completed only 12 months after hormone replacement, accompanied by the presence of vertebral osteophytes and coxofemoral osteoarticular alterations. Considering chronic use of progestins, ovariosalpingohysterectomy (OSH) was recommended, but for personal reasons, the owners chose to do not submit her to surgery. After 18 months of treatment, the dog starts to exhibit prostration, selective appetite, and increased abdominal volume. After imaging exam, she was forwarded for OSH, due to consistent findings of pyometra. Subsequently, even the supervision of possible comorbidities involved in the chronic use of progestins was maintained at half-yearly intervals, the bitch returned to the service with skin thickening, increased limb volume, and macroglossia after 60 months of therapy. At this point IGF-1 values were higher when compared to the previous measurements and the application of medroxyprogesterone was suspended. Its supplementation was reintroduced only after 8 months when IGF-1 was significantly reduced. To date, the patient is close to 6 years of age and with a good quality of life. Discussion: The greatest therapeutic challenge for these patients involves dealing with the adverse effects of progestins, mainly related to reproductive disorders and alopecia at the application site, as well as maintaining adequate hormone replacement in order to avoid hypersomatotropism. Although longevity is lower in these individuals, the patient in this report has achieved 6 years of age and has had an excellent quality of life so far.

Prenatal diagnosis of diastrophic dysplasia in the second trimester of pregnancy: Two- and three- dimensional ultrasonographic findings

To present a prenatal diagnosis of diastrophic dysplasia in the second trimester of pregnancy using two- (2D) and three-dimensional (3D) ultrasonography. The mother was primigravida and aged 12 years. She underwent the first 2D obstetric ultrasound examination at 27 weeks, showing bilaterally upper and lower limb micromelia, thumb and hallux in bilateral abduction, bilateral talipes equinovarus; hyperlordosis of the lumbar spine, cervical, lumbar, and sacral scoliosis; cervical hyperkyphosis with the misalignment of cervical vertebrae, and straight clavicles. 3D ultrasonography in conventional and HDlive rendering modes confirmed the changes observed in 2D ultrasonography and allowed improved understanding by the parents. At birth, the newborn presented transient respiratory distress and neonatal sepsis. At the time of writing, the child is aged 31 months and under follow-up by the pediatrics department. 3D ultrasound allowed the parents to understand the fetal malformations better, and they received adequate counseling.

When size matters: the first comprehensive anatomical study of a species of "Condylocardiidae", an extremely miniaturized bivalve.

'Miniaturization' is a widespread phenomenon among the Metazoa. In the molluscan class Bivalvia, records of miniaturization are numerous. Among the Archiheterodonta, Warrana besnardi (Klappenbach, 1963) has attracted attention for its tiny size, which does not exceed 1.5 mm in shell length, and because it belongs to a group with limited anatomical information and often-debated status, the "Condylocardiidae" (which recent molecular studies place deeply nested within the family Carditidae). All species of Warrana Laseron, 1953 are small-bodied, and so miniaturization presumably occurred from a large-bodied ancestor within the Carditidae sensu lato. South American W. besnardi is here studied in detail. Its small size and the enlargement of the anterodorsal region during growth, reflects (and likely led) to infaunal habit, living as a burrowing bivalve that passively feeds on deposit particles entering the pallial cavity anteriorly. Mantle glands, previously reported as a common feature of other archiheterodonts, are missing in W. besnardi, but spongiform tissue in the antero-ventral portion of the mantle lobes presumably represents a blood sinus that might compensate for the great reduction of the ctenidia. Lecithotrophy is reported, with yolky oocytes bearing a thick non-cellular capsule layer; brooding was not observed, and it is here hypothesized that the extreme miniaturization, with the great reduction of ctenidia, is responsible for a shift in the reproductive mode of condylocardiids, contrasting with the commonly reported ovoviviparity of the carditids.

Déficit de hormona del crecimiento como causa de baja talla / Loss growth hormone as cause of short stature

RESUMEN Fundamento: la talla baja supone un motivo de preocupación para los padres y es una causa muy frecuente de consulta en Pediatría y en Endocrinología Pediátrica. Objetivo: presentar el caso de un adolescente con baja talla por déficit de hormona del crecimiento. Presentación del caso: paciente adolescente de 12 años de edad que acude a consulta de Endocrinología por baja talla con examen físico normal y dosificaciones de hormona del crecimiento bajas en dos estudios de estimulación (test de clonidina e hipoglucemia inducida por insulina). Conclusiones: la baja talla por déficit de hormona del crecimiento es una de las causas corregibles de este trastorno.

ABSTRACT Background: short stature is a common cause of preoccupation in parents and it's a frequent shift complaint at Pediatric Endocrinology. Objective: to show the case of a teenager who had short stature due to loss growth hormone. Case report: a 12 years-old male teenager who came to Endocrinologist because of a short stature. Physical exam was normal meanwhile hormonal lab test shown loss growth hormone on two stimulated test (clonidine test and insulin-induced hypoglycemia). Conclusions: short stature due to loss growth hormone is a latent corrigible cause of that disorder.

Aggrecan, IL-1ß, IL-6, and TNF-α profiles in the Articular Cartilage of Miniature Horses with Chondrodysplastic Dwarfism.

Dwarfism is a skeletal disorder that causes abnormal growth. In Miniature horses, dwarfism can occur as chondrodysplastic dwarfism, an autosomal recessive disorder associated with five mutations (D1, D2, D3*, D4 and c.6465A > T variant) in the aggrecan (ACAN) gene. The aim of this study was to evaluate the expression of aggrecan (at the gene and protein level) and specific cytokines (IL-1ß, IL-6, and TNF-α) in the articular cartilage of Miniature horses with chondrodysplastic dwarfism (D4/c.6465A > T genotype). Metatarsal bone samples from eight dwarf Miniature horses were collected for histopathological analysis, and articular cartilage was collected to detect and quantify aggrecan levels through Western blotting and determine the relative expression levels of ACAN, IL-1ß, IL-6, and TNF-α through qPCR. All affected animals presented chondrodysplasia-like lesions with disorganization of the chondrocyte layers and reduced the amount of an extracellular matrix. No significant difference in aggrecan expression levels in uncleaved samples from the dwarf and control groups (composed of phenotypically normal animals of similar age and breed (P = .7143)) was found using Western blotting. qPCR revealed that ACAN gene expression was higher in the affected animals than in normal animals (P = .0119). No significant difference in cytokine levels was detected between the groups. Mutant aggrecan may interfere with normal cellular function, leading to chondrodysplasia and the observed phenotypic findings.

Evolutionary treasures hidden in the West Indies: Comparative osteology and visceral morphology reveals intricate miniaturization in the insular genera Mitophis Hedges, Adalsteinsson, & Branch, 2009 and Tetracheilostoma Jan, 1861 (Leptotyphlopidae: Epictinae: Tetracheilostomina).

The genera Mitophis and Tetracheilostoma comprise two extant lineages of small-sized threadsnakes that exclusively inhabit several islands of the West Indies. Even though leptotyphlopids are known for their extremely reduced size, miniaturization has only been hypothesized to reflect insular dwarfism for the genus Tetracheilostoma. Herein, we aim to describe the comparative osteology and visceral morphology of both genera, investigating and discussing their several internal morphological simplifications and novelties. Our results indicate that these taxa exhibit several autapomorphies mostly concentrated in the dorsoposterior skull elements and maxillae, as well as in their axial skeleton and viscera. These novelties and simplifications are most likely a result of extreme miniaturization driven by the evolutionary constraints or ecological opportunities possibly imposed by the "island rule." Both Mitophis and Tetracheilostoma distinguish from all other Epictinae in lacking a dentigerous process in the maxillae, by having the prootic fused to the otooccipital, and by the lack (except in comparison to a few Epictia) of a cervical vertebrae intercentrum I. Additionally, Mitophis can be distinguished from other Epictinae by the participation of the unpaired supraoccipital in the dorsal border of the foramen magnum, by the absence of the pleurapophyses in the caudal vertebrae, by a higher number of liver segments, and by the extreme degeneration of the pelvic rudiments. Tetracheilostoma differs from other Epictinae by lacking a distinct supraoccipital, which is fused to the parietal. Thus, our results reinforce that morphological characters are extremely valuable for leptotyphlopid systematics given their extremely conserved external morphology.

Circulating microRNA profile in humans and mice with congenital GH deficiency.

Reduced inflammation, increased insulin sensitivity, and protection against cancer are shared between humans and mice with GH/IGF1 deficiency. Beyond hormone levels, miRNAs are important regulators of metabolic changes associated with healthy aging. We hypothesized that GH deficiency in humans alters the abundance of circulating miRNAs and that a subset of those miRNAs may overlap with those found in GH-deficient mice. In this study, subjects with untreated congenital isolated GH deficiency (IGHD; n = 23) and control subjects matched by age and sex (n = 23) were recruited and serum was collected for miRNA sequencing. Serum miRNAs from young (6 month) and old (22 month) Ames dwarf (df/df) mice with GH deficiency and their WT littermates (n = 5/age/genotype group) were used for comparison. We observed 14 miRNAs regulated with a genotype by age effect and 19 miRNAs regulated with a genotype effect independent of age in serum of IGHD subjects. These regulated miRNAs are known for targeting pathways associated with longevity such as mTOR, insulin signaling, and FoxO. The aging function was overrepresented in IGHD individuals, mediated by hsa-miR-31, hsa-miR-146b, hsa-miR-30e, hsa-miR-100, hsa-miR-181b-2, hsa-miR-195, and hsa-miR-181b-1, which target the FoxO and mTOR pathways. Intriguingly, miR-181b-5p, miR-361-3p, miR-144-3p, and miR-155-5p were commonly regulated in the serum of humans and GH-deficient mice. In vitro assays confirmed target genes for the main up-regulated miRNAs, suggesting miRNAs regulated in IGHD individuals can regulate the expression of age-related genes. These findings indicate that systemic miRNAs regulated in IGHD individuals target pathways involved in aging in both humans and mice.

Artificial neural networks and genetic dissimilarity among saladette type dwarf tomato plant populations.

Studies have shown that dwarf plants have the potential for use in obtaining hybrids. The aim of this study was to evaluate the agronomic potential and genetic dissimilarity of saladette type dwarf tomato plant populations through the use of artificial neural networks (ANNs). The following traits were analyzed: mean fruit weight, transverse and longitudinal fruit diameter, fruit shape, pulp thickness, locule number, internode length, soluble solids content, and ß-carotene, lycopene, and leaf zingiberene contents. A dendrogram obtained by the unweighted pair-group method with arithmetic mean (UPGMA) and Kohonen self-organizing maps (SOM) agreed in the distinction of the BC1F3 populations from the dwarf donor parent. SOM was more consistent in identifying the genetic similarities among the BC1F3 dwarf tomato plant populations and allowed for the determination of weights of each variable in the cluster formation. The UFU SDi 13-1 BC1F3 population was revealed to be a promising option for obtaining saladette type dwarf tomato plant lines.

Síndrome de Ellis Van Creveld / Ellis Van Creveld syndrome

Resumen El síndrome de Ellis van Creveld es un trastorno autosómico recesivo, caracterizado por mutaciones en los genes ECV y ECV2, los cuales son importantes para el desarrollo osteocondral. A nivel mundial, se han reportado aproximadamente 300 casos ,presentándose con mayor frecuencia en poblaciones endogámicas. Se caracteriza por distrofias óseas, displasias ectodérmicas y malformaciones cardíacas. El diagnóstico clínico puede ser confirmado mediante pruebas moleculares. A continuación, se presenta el caso de una paciente diagnosticada con el síndrome, la cual fue evaluada de manera interdisciplinaria. Esta revisión permitió dar a conocer un nuevo caso de la patología, relacionar las manifestaciones clínicas de la paciente con la literatura y describir nuevos hallazgos que pueden correlacionarse con el síndrome.

Abstract Ellis Van Creveld syndrome is an autosomal recessive disorder, characterized by mutations of the genes ECV and ECV2, which are very important in the osteochondral development. Worldwide, there have been reported around 300 cases that are commonly evidenced in populations where endogamy is typical. It is clinically characterized by bone dystrophies, ectodermal dysplasias, and congenital heart defects; the diagnosis can be confirmed by molecular tests. In the lines below, a case of a patient that suffers from this syndrome, and that was examined in an interdisciplinary way will be presented. This review allows us to show a new case of this pathology, to relate the clinical symptoms of the patient with the existing literature, and to describe new findings that can be correlated with the Ellis Van Creveld condition.

Evidence of pituitary hypoplasia associated with partial central diabetes insipidus in a young Persian cat

Background: Congenital anomalies are an uncommon pituitary hypofunction cause associated to multiple hormone deficiencies. Congenital hyposomatotropism is often related to an inherited anomaly, characterized mainly by delayed growth. It is not uncommon to find associated thyroid-stimulating hormone and gonadotropin deficiencies. Pituitary malformation may be associated to progressive cystic lesion expansion. Central diabetes insipidus (CDI) is another rare disease associated to polyuria (PU) and polydipsia (PD) secondary to antidiuretic hormone (ADH) deficient secretion. The aim of this report is to describe a likely case of pituitary hypoplasia, associated with partial CDI in a cat. Case: A 9-month-old unneutered male Persian cat weighing 2 kg was presented due to severe polyuria and polydipsia associated with growth deficit when compared with its sibling. After clinical and laboratory evaluations during the months in which the patient was monitored, reduced serum concentration of insulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), thyroid hormones, and testosterone were documented, confirming the diagnosis of hyposomatotropism, hypogonadism, and secondary hypothyroidism. Furthermore, therapeutic diagnosis with desmopressin revealed partial central diabetes insipidus (CDI). As the sibling showed normal development aging 13-months, a radiographic examination of the forelimb (carpus) was performed on both cats. There was lack of growth plate fusion in the patient, without any other evidence of dysgenesis, whereas complete epiphyseal closure was observed in the sibling. Despite therapeutic prescriptions of desmopressin and levothyroxine, the owners refused further follow-up to the...(AU)

Discondrosteosis de Léri-Weill. Presentación de una familia afectada / Léri-Weill dyschondrosteosis. Presentation of an affected family

RESUMEN Fundamentación: La discondrosteosis de Léri-Weill, displasia ósea de origen genético que afecta la región mesomélica con acortamiento de las extremidades, provoca talla baja con extremidades cortas con deformidad de Madelung; esta enfermedad muestra un patrón de herencia autosómico dominante con alta penetrancia. Objetivo: Describir las deformidades de esta discondrosteosis de baja frecuencia con expresividad variable, que se presentó de la misma forma en todos los afectados de esta familia. Presentación de caso: Se reportó una familia con enfermos en tres generaciones con deformidad de Madelung de ambas muñecas y baja estatura de origen mesomélico, que se mantiene seguimiento en consultas de Genética Clínica y Ortopedia. Conclusiones: El examen físico y radiológico imprescindibles para llegar al diagnóstico clínico. El método clínico y la valoración multidisciplinaria resultaron de gran valor para definir esta enfermedad y poder brindar un adecuado asesoramiento genético a esta familia.

ABSTRACT Background: Léri-Weill dyschondrosteosis, bone dysplasia of genetic origin that affects the mesomelic region with shortening of the extremities, causes short stature with short extremities with Madelung deformity.This disease shows an autosomal dominant inheritance pattern with high penetrance. Objective: To describe the deformities of this low frequency dyschondrosteosis with variable expressivity which was presented in the same way in all those affected in this family. Case presentation: A family with sick members was reported in three generations with Madelung deformity of both wrists and short stature of mesomelic origin which is followed up in consultations of Clinical Genetics and Orthopedics. Conclusion: The essential physical and radiological examination to reach the clinical diagnosis. The clinical method and the multidisciplinary assessment were of great value to define this disease and to be able to provide adequate genetic counseling to this family.

Chondrodysplasia Bulldog type in cattle in the state of Bahia, Brazil

Chondrodysplasia is a congenital or hereditary disorder of the endochondral ossification that results in several degrees of disproportionate dwarfism. Reports of this disease are scarce in the national literature and do not emphasize radiographic characteristics. The goal of this study was to describe the clinicopathological and radiographic aspects of a case of Bulldog type chondrodysplasia in a crossbred bovine fetus in the state of Bahia, Brazil. The fetus exhibited arounded and disproportionate skull, bilateral exophthalmos, inferior brachygnathism, partial tongue protrusion, extremely short limbs, short vertebral column and ventral abdominal hernia. Radiographic evaluation revealed that the diaphysis were the only calcified bone portions of the limbs, that the vertebral column was shortened without vertebral spinal processes and that there was craniofacial disproportion. Microscopic of the femur showed an irregular epiphyseal plaque, formed by denseclusters of chondrocytes with absence of growth plate zones. The metaphysis was markedly short and consisted of thick bony trabeculae, surrounded by cartilaginous islands. It was concluded that fetuses with Bulldog type chondrodysplasia exhibit slight morphological and radiographic variation according to the affected breed and that the gene carrier of chondrodysplasia is present in the miniature Jersey and Punganur population in the state of Bahia.(AU)

Chondrodysplasia Bulldog type in cattle in the state of Bahia, Brazil

Chondrodysplasia is a congenital or hereditary disorder of the endochondral ossification that results in several degrees of disproportionate dwarfism. Reports of this disease are scarce in the national literature and do not emphasize radiographic characteristics. The goal of this study was to describe the clinicopathological and radiographic aspects of a case of Bulldog type chondrodysplasia in a crossbred bovine fetus in the state of Bahia, Brazil. The fetus exhibited arounded and disproportionate skull, bilateral exophthalmos, inferior brachygnathism, partial tongue protrusion, extremely short limbs, short vertebral column and ventral abdominal hernia. Radiographic evaluation revealed that the diaphysis were the only calcified bone portions of the limbs, that the vertebral column was shortened without vertebral spinal processes and that there was craniofacial disproportion. Microscopic of the femur showed an irregular epiphyseal plaque, formed by denseclusters of chondrocytes with absence of growth plate zones. The metaphysis was markedly short and consisted of thick bony trabeculae, surrounded by cartilaginous islands. It was concluded that fetuses with Bulldog type chondrodysplasia exhibit slight morphological and radiographic variation according to the affected breed and that the gene carrier of chondrodysplasia is present in the miniature Jersey and Punganur population in the state of Bahia.

Description of the D4/D4 genotype in Miniature horses with dwarfism.

Four causative mutations (D1, D2, D3*, and D4) of chondrodysplastic dwarfism have been described in the equine aggrecan (ACAN) gene. Homozygotes for one of these mutations and heterozygotes for any combination of these mutations exhibit the disproportionate dwarfism phenotype. However, no case description of homozygotes for D4 (D4/D4) has been reported in the literature, to our knowledge. We report 2 Miniature horses with the genotype D4/D4 in the ACAN gene. Clinically, the 2 dwarfs had a domed head that was large compared to the rest of the body, mandibular prognathism, and short and bowed limbs, mainly in the proximal region of the metatarsal bones. Radiographic examination revealed contour irregularities of the subchondral bone in the long bones and confirmed mandibular prognathism; histopathology revealed irregular chondrocyte organization. To determine the genotypes of the horses, we performed DNA extraction from white blood cells, PCR, and Sanger sequencing. Genotyping demonstrated that these 2 animals had the D4/D4 genotype in the ACAN gene. The D4/D4 dwarfs were clinically similar to animals with the other ACAN genotypes reported for this disease. Identification of heterozygous animals makes mating selection possible and is the most important control measure to minimize economic losses and casualties.

Evidence of pituitary hypoplasia associated with partial central diabetes insipidus in a young Persian cat

Background: Congenital anomalies are an uncommon pituitary hypofunction cause associated to multiple hormone deficiencies. Congenital hyposomatotropism is often related to an inherited anomaly, characterized mainly by delayed growth. It is not uncommon to find associated thyroid-stimulating hormone and gonadotropin deficiencies. Pituitary malformation may be associated to progressive cystic lesion expansion. Central diabetes insipidus (CDI) is another rare disease associated to polyuria (PU) and polydipsia (PD) secondary to antidiuretic hormone (ADH) deficient secretion. The aim of this report is to describe a likely case of pituitary hypoplasia, associated with partial CDI in a cat. Case: A 9-month-old unneutered male Persian cat weighing 2 kg was presented due to severe polyuria and polydipsia associated with growth deficit when compared with its sibling. After clinical and laboratory evaluations during the months in which the patient was monitored, reduced serum concentration of insulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), thyroid hormones, and testosterone were documented, confirming the diagnosis of hyposomatotropism, hypogonadism, and secondary hypothyroidism. Furthermore, therapeutic diagnosis with desmopressin revealed partial central diabetes insipidus (CDI). As the sibling showed normal development aging 13-months, a radiographic examination of the forelimb (carpus) was performed on both cats. There was lack of growth plate fusion in the patient, without any other evidence of dysgenesis, whereas complete epiphyseal closure was observed in the sibling. Despite therapeutic prescriptions of desmopressin and levothyroxine, the owners refused further follow-up to the...

From dwarves to giants: South American's contribution to the history of growth hormone and related disorders.

The aim of this article is to present a historical review on giants and dwarves living in South America and the contribution of South America's researchers to scientific advances on growth hormone (GH) and human disorders related to GH excess and GH deficiency (GHD). We went back in time to investigate facts and myths stemming from countless reports of giants who lived in the Patagonia region, focusing on what is currently known about gigantism in South America. Additionally, we have reviewed the exceptional work carried out in two of the world's largest cohorts of dwarfism related to GH-IGF axis: one living in Itabaianinha, Brazil, suffering from severe GHD due to a mutation in the GHRH receptor (GHRHR) gene, and the other living in El Oro and Loja provinces of Ecuador, who are carriers of GH receptor gene mutation that causes total GH insensitivity (Laron syndrome). Importantly, we present an overview of the outstanding medical contribution of Jose Dantas de Souza Leite, a Brazilian physician that described the first cases of acromegaly, and Bernardo Alberto Houssay, an Argentine researcher graced with the Nobel Prize, who was one the first scientists to establish a link between GH and glucose metabolism.

Alteraciones estomatognáticas del síndrome 3M: reporte de dos casos / Stomatognathic alterations of 3m syndrome: two cases report

Resumen El síndrome 3M es un desorden autosómico recesivo, heterogéneo, poco común, llamado así por los tres investigadores que lo describieron por primera vez, Miller, Mckusck y Malvaux. Las características principales son retraso en el crecimiento prenatal y postnatal severo, dismorfias faciales y anomalías radiológicas. En sus manifestaciones estomatológicas presentan dolicocefalia, abombamiento frontal, cara triangular, labios gruesos, cejas pobladas, hipoplasia maxilar severa, facies melancólicas, retraso en la erupción dental severa y falta de crecimiento del macizo facial. El objetivo del artículo es la descripción de casos gemelares de 8 años y 6 meses de edad, que acuden a la Clínica de Atención Dental Avanzada de la Universidad de Monterrey, con confirmación del síndrome 3M por prueba sanguínea a los 4 años de edad por parte del Servicio de Genética del Hospital Universitario. Se realiza rehabilitación bucal de ambas niñas, y, posteriormente, son referidas a interconsulta con ortodoncia interceptiva. MÉD.UIS.2019;32(2): 59-65

Abstract 3M syndrome is very rare, it's a heterogeneous autosomal recessive disorder named after 3 researches who described it for the first time, Miller, Mckusck and Malvaux. Whose main characteristic are; delayed prenatal growth, severe postnatal growth, facial dysmorphia, radiological abnormalities, presence of dolichocephaly, frontal bulging, triangular face, thick lips, raised eyebrows, severe maxillary hypoplasia, melancholic facies, delayed severe dental eruption, lack of facial mass growth. The objective of the article is the description of twin cases that come to the Advanced Dental Care Clinic of the University of Monterrey; 8 years 6 months old, with confirmation of the 3M syndrome, with a blood test at 4 years of age by the Genetics Service of the University Hospital. MÉD.UIS.2019;32(2): 59-65

Hormona de crecimiento en sangre de papel filtro para el diagnóstico de deficiencia de hormona de crecimiento / Growth hormone of dried blood spot for the diagnosis of growth hormone deficiency

INTRODUCCIÓN: El diagnóstico de deficiencia de hormona de crecimiento (DHC) es difícil de establecer, y se puede asociar a serias complicaciones, especialmente en el período neonatal. La prueba de estímulo de secreción de hormona de crecimiento (HC) se considera de elección para el diagnóstico, pero presenta complicaciones metodológicas y se asocia a efectos adversos. Los neonatos presentan aumento de la secreción de HC de forma fisiológica, siendo una ventana diagnóstica. OBJETIVO: Evaluar si la muestra de sangre en papel filtro tomada en el período neonatal, en contexto del tamizaje neonatal de hipotiroidismo congénito y fenilcetonuria, permite diferenciar pacientes con DHC, de los que no la presentan. PACIENTES Y MÉTODO: Estudio de casos y controles mediante determinación de concentración de HC en sangre de papel filtro extraída en período neonatal, comparando controles con DHC con casos con deficiencia descartada. Se realizó extracción de la muestra del papel filtro, obteniendo dos discos de 0,125 pulgada por cada uno de los pacientes desde el centro de la mancha de sangre del papel, para un ELISA de HC humana altamente sensible basado en el uso de anticuerpos policlonales dirigidos contra la HC humana recombinante de 22kDa de peso molecular. RESULTADOS: Se obtuvo un total de 7 casos de DHC y 10 controles. La mediana de concentración de HC de papel filtro en los casos es 2,0 ng/ml (Rango intercuartil 3,6 ng/ml) y controles 2,05 ng/mL (RIC 2,0 ng/ml), U de Mann-Withney 30,5 (p = 0,68). Los dos casos con deficiencia de hormonas hipofisarias múltiples (DHHM) presentan concentraciones menores a 1 ng/ml. CONCLUSIÓN: La muestra de papel filtro no permitió diferenciar a los pacientes con DHC de los casos controles, aunque los casos con DHHM presentaron concentraciones mucho menores, en comparación a la deficiencia de hormona de crecimiento aislada (DHCA).

INTRODUCTION: The diagnosis of growth hormone deficiency (GHD) is difficult to determine, and could be associated with severe complications, especially in the neonatal period. The stimulation test of growth hormone (GH) secretion is considered the gold standard for diagnosis, but it has methodological complications and is associated with adverse effects. Neonates present physiological increased secretion of GH, representing a diagnostic window. OBJECTIVE: To evaluate if the dried blood spot on filter paper obtained in the neonatal period, as part of a neonatal screening for con genital hypothyroidism and phenylketonuria, allows differentiating patients with GHD from those who do not have it. PATIENTS AND METHOD: Study of cases and controls by measuring the GH concen tration in dried blood spot on filter paper obtained in the neonatal period, comparing controls with GHD with cases with discarded deficiency. The sample was extracted from the filter paper, obtaining two 0.125 inch discs per each patient from the center of the blood spot on the paper, for a highly sen sitive ELISA assay for human GH based on the use of polyclonal antibodies against 22 kDa recom binant human GH. RESULTS: Seven cases of GHD and ten controls were obtained. The median GH concentration of the dried blood spot in the cases is 2.0 ng/ml (Interquartile range 3.6 ng/ml) and 2.05 ng/ml (Interquartile range 2.0 ng/ml) in the controls, Mann-Whitney U test 30.5 (p = 0.68). The two cases with multiple pituitary-hormone deficiency (MPHD) present concentrations lower than 1 ng/ml. CONCLUSION: The dried blood spot sample did not differentiate GHD patients from control cases, although MPHD cases present much lower concentrations compared to isolated growth hor mone deficiency (IGHD).