ABSTRACT
Léri-Weill dyschondrosteosis (LWD) has typical triad: short middle limbs, short stature, Madelung deformity of wrist, and increased body mass index. Short stature and high body mass index are risk factors for metabolic syndrome, type 2 diabetes, cardiovascular diseases, and autoimmune thyroid diseases. However, metabolic disorders and thyroid diseases in adult LWD patients have not been elucidated. This paper reports two adult patients with LWD presented to the Department of Endocrinology and metabolism. By introducing clinical characteristics, genetic variations, and diagnostic methods, physicians can deepen their understanding of LWD, improve diagnosis, and be aware of the comorbid metabolic diseases and thyroid disorders with a view of early prevention and treatment.
ABSTRACT
La deformidad de Madelung es una alteración poco común de la articulación de las muñecas. Se vincula a mutaciones del gen SHOX y se caracteriza por alteraciones en el radio, carpo y cúbito, con predominio bilateral. Afecta principalmente a pacientes de sexo femenino y aparece al inicio de la adolescencia. Se presenta una paciente de 15 años de edad, con antecedentes de problemas de salud. Al entrar en la adolescencia comenzó a presentar deformidad en ambas muñecas, más marcada en el lado derecho acompañado de dolor. El diagnóstico de deformidad de Madelung se concluyó mediante la clínica asociado a la positividad de los estudios imagenológicos, basados en los criterios radiográficos de Dannenberg y otros. Se decidió tratamiento quirúrgico, mediante osteotomía doble correctora para longitud y fijación externa de la mano derecha, con la resolución completa de la deformidad y seguimiento en la Consulta Externa de Ortopedia(AU)
Madelung's deformity is a rare alteration of the wrist joint. It is linked to mutations of the SHOX gene. It is characterized by alterations in the radius, carpus and ulna, predominantly bilateral. It mainly affects female patients; signs and symptoms are evident at the beginning of adolescence. To present a case of a patient with a diagnosis of Madelung deformity. The case of a 15-year-old female patient with a health history and family history of interest of an equine clubfoot father is presented. When she entered adolescence, she began to present deformity in both wrists, more marked in the right side accompanied by pain. This is a patient with a Madelung deformity. The diagnosis was concluded by the clinic associated with the positivity of the imaging studies(AU)
Subject(s)
Humans , Female , Adolescent , Congenital Abnormalities , Lipomatosis, Multiple Symmetrical/surgery , Lipomatosis, Multiple Symmetrical/congenital , Lipomatosis, Multiple Symmetrical/diagnostic imaging , Signs and SymptomsABSTRACT
PURPOSE: Short stature affects approximately 2%–3% of children, representing one of the most frequent disorders for which clinical attention is sought during childhood. Despite assumed genetic heterogeneity, mutations or deletions in the short stature homeobox-containing gene (SHOX) are frequently detected in subjects with short stature. Idiopathic short stature (ISS) refers to patients with short stature for various unknown reasons. The goal of this study was to screen all the exons of SHOX to identify related mutations. METHODS: We screened all the exons of SHOX for mutations analysis in 105 ISS children patients (57 girls and 48 boys) living in Taif governorate, KSA using a direct DNA sequencing method. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. RESULTS: A total of 30 of 105 ISS patients (28%) contained six polymorphic variants in exons 1, 2, 4, and 6. One mutation was found in the DNA domain binding region of exon 4. Three of these polymorphic variants were novel, while the others were reported previously. There were no significant differences in anthropometric measures in ISS patients with and without identifiable polymorphic variants in SHOX. CONCLUSION: In Saudi Arabia ISS patients, rather than SHOX, it is possible that new genes are involved in longitudinal growth. Additional molecular analysis is required to diagnose and understand the etiology of this disease.
Subject(s)
Child , Female , Humans , Arm , DNA , Exons , Genetic Heterogeneity , Leg , Mass Screening , Methods , Saudi Arabia , Sequence Analysis, DNAABSTRACT
OBJETIVOS: Descrever um caso de Discondrosteose de Léri-Weill, uma displasia óssea hereditária rara, frequentemente associada a uma haploinsuficiência do gene SHOX (short stature homeobox-containing). DESCRIÇÃO DO CASO: Criança de três anos, sexo feminino, enviada à consulta de pediatria por suspeita de hipertensão arterial. Antecedentes pessoais e familiares irrelevantes. Ao exame físico apresentava aspeto dismórfico, com encurtamento dos membros superiores e inferiores, mãos e pés pequenos e pescoço curto. A hipertensão arterial não foi confirmada. O estudo genético para excluir cromossomopatia revelou mutações no gene SHOX compatíveis com Discondrosteose de Léri-Wei. CONCLUSÕES: O exame físico é fundamental na prática clínica, permitindo identificar alterações importantes que nem sempre são o motivo da consulta. Na Discondrosteose de Léri-Weill o pronto diagnóstico e a orientação adequada são fundamentais, sobretudo pelas implicações terapêuticas desse distúrbio, que apresenta evolução favorável se tratado com hormônio do crescimento.
AIMS: To report a case of Léri-Weill dyschondrosteosis, a rare hereditary bone dysplasia often associated with a haploinsufficiency of the SHOX (short stature homeobox-containing) gene. CASE DESCRIPTION: A three-year-old female had sought medical care for hypertension. Irrelevant personal and family background. The physical examination showed dysmorphic aspect with shortening of arms and legs, small hands and feet, and short neck. Hypertension was not confirmed. Genetic study for chromosomal deletion syndromes revealed mutations in the SHOX gene compatible with Léri-Weill dyschondrosteosis. CONCLUSIONS: Physical examination is essential in clinical practice, allowing the identification of majorchanges that are not always the reason for the medical appointment. Early diagnosis and proper guidance are essential in Léri-Weill dyschondrosteosis, especially because of its therapeutic implications. The outcome is favorable if the disorder is treated with growth hormone therapy.
Subject(s)
Female , Child, Preschool , Genetic Diseases, Inborn , Physical Examination , Failure to ThriveABSTRACT
Objective To investigate the effect of short stature homeobox (SHOX) gene promoter-372G →A mutation on the promoter activity and its mechanism.Methods The luciferase report gene vectors containing human SHOX gene promoter-372G or -372A were contructed.Their transcription activities were detected in chicken chondrocytes.Double-stranded DNA probes containing-372G or-372A were produced by PCR,and used for detecting the affinity with nuclear transcription factors by electrophoretic mobility shift assay(EMSA).Results The transcription activity in a-372A promoter construct was significantly higher than that in the wild type-372G (P<0.01).The result of EMSA showed that-372A gene mutation resulted in loss of the binding affinity to nuclear transcription factors.Conclusion The-372A mutation increases SHOX promoter activity with decreased DNA binding affinity to transcription factors,which may contribute to impaired long bone growth in patients with idio pathic short stature.
ABSTRACT
We report on a girl presenting Léri-Weill dyschondrosteosis (LWD) due to deletion of the SHOX gene. Her family included individuals with short stature alone or with both short stature and mesomelia or Madelung's deformity. The deletion was demonstrated through detection of hemizygosity for microsatellite markers SHOX-CA repeat, DXYS10092, DXYS10093 and DXYS10091 localized around the SHOX gene, with retention of paternal alleles in the proband and three of her sisters who had short stature as the only clinical feature. Hemizygosity for these loci was also observed in their mother, who had short stature too. The deletion in the proband was however larger, including locus DXY10083. The proband's only sister with normal height did not carry the deletion. Family history suggests transmission of the deletion from the proband's maternal great-grandfather to her grandfather via the Y chromosome, and from the grandfather to the proband's mother via the X chromosome after crossing-over in the pseudoautosomal region proximal to the SHOX gene.
Subject(s)
Humans , Male , Female , Child , Adult , Genes, Dominant , Genes, Homeobox , Osteochondrodysplasias/genetics , Genotype , Lipomatosis, Multiple Symmetrical , Microsatellite RepeatsABSTRACT
La talla baja es una condición que afecta el crecimiento lineal en el proceso de desarrollo del individuo es ocasionada por múltiples factores pero con un fuerte componente genético. En los últimos años, se ha incrementado el conocimiento de las causas genéticamente determinadas de talla baja debido a reporte de pacientes con características especiales, quienes han ofrecido una excelente oportunidad para estudiar genes que juegan un papel crucial en el crecimiento. En esta revisión se delinea, desde la perspectiva de un médico genetista, un flujograma diagnóstico a ser considerado en todo paciente con talla baja.
Short stature is a condition affecting the body growth in the development process of an individual which is caused by multiples factors, but with a strong component genetic. In the last few years, our knowledge of genetically determined causes of short stature has greatly increased by reports of challenging patients, who offered the opportunity to study genes that play a role in growth. In this review, a diagnostic flow chart is delinead to consider in all patients with short stature from the perspective of a medical geneticist.