El síndrome 22q11.2D S como un subtipo genético de esquizofrenia / 22q11.2 DS Syndrome as a Genetic Subtype of Schizophrenia

Introducción: El síndrome de deleción 22q11.2 (22q11.2 DS) se produce por microdeleciones del brazo largo del cromosoma 22 en la región q11.2. Después del síndrome de Down, es el segundo síndrome genético más común. En pacientes con esquizofrenia, el 22q11.2 DS tiene una prevalencia del 2%, mientras que en personas con esquizofrenia seleccionadas por características físicas específicas, aumenta un 32-53%. Objetivo: Describir las generalidades del 22q11.2 DS, sus características clínicas, los aspectos genético-moleculares y la frecuencia de la microdeleción de 22q11.2 en diferentes poblaciones. Métodos: Se hizo una revisión desde 1967 hasta 2013 en bases de datos de publicaciones científicas, orientada a recopilar artículos sobre el 22q11.2 DS y su relación con la esquizofrenia. Resultados: El 22q11.2 DS es una entidad genética que se asocia a un fenotipo variable relacionado con defectos congénitos en diferentes tejidos y órganos, así como a una alta frecuencia de trastornos psiquiátricos, particularmente la esquizofrenia. Se ha identificado alta prevalencia en grupos de personas con esquizofrenia seleccionadas por características sindrómicas comunes, como dificultades de aprendizaje, rasgos faciales típicos, anomalías palatales y defectos cardiacos congénitos. Las técnicas de FISH, qPCR, MLPA y, recientemente, aCGH y NGS se están usando para diagnosticar esta microdeleción. Conclusiones: En la práctica clínica es importante tener presente que las personas con 22q11.2 DS tienen alto riesgo de sufrir esquizofrenia, ya que la región 22q11.2 alberga genes candidatos relacionados con vulnerabilidad a esquizofrenia. Se considera que la concomitancia de esta enfermedad y 22q11.2 DS representa un subtipo genético de esquizofrenia. y métodos citogenéticos y moleculares para diagnosticar a este grupo de pacientes y optimizar un abordaje multidisciplinario en su seguimiento.

Introduction: The 22q11.2 deletion syndrome (22q11.2 DS) is associated with the microdeletion of this chromosomal region, and represents the second most common genetic syndrome after Down's syndrome. In patients with schizophrenia, 22q11.2 DS has a prevalence of 2%, and in selected groups can be increased to between 32-53%. Objective: To describe the generalities of 22q11.2 DS syndrome as a genetic subtype of schizophrenia, its clinical characteristics, molecular genetic aspects, and frequency in different populations. Methods: A review was performed from 1967 to 2013 in scientific databases, compiling articles about 22q11.2 DS syndrome and its association with schizophrenia. Results: The 22q11.2 DS syndrome has a variable phenotype associated with other genetic syndromes, birth defects in many tissues and organs, and a high rate of psychiatric disorders, particularly schizophrenia. Likewise, it has been identified in clinical populations with schizophrenia selected by the presence of common syndromic characteristics. FISH, qPCR and MLPA techniques, and recently, aCGH and NGS technologies, are being used to diagnose this microdeletion. Conclusions: It is important in clinical practice to remember that people suffering the 22q11.2 DS have a high genetic risk for developing schizophrenia, and it is considered that the simultaneous presence of this disease and 22q11.2 DS represents a genetic subtype of schizophrenia. There are clear phenotypic criteria, molecular and cytogenetic methods to diagnose this group of patients, and to optimize a multidisciplinary approach in their monitoring.

A Case of DiGeorge Syndrome with Metopic Synostosis

PURPOSE: We report a patient with DiGeorge syndrome who was later diagnosed as mild metopic synostosis and received anterior 2/3 calvarial remodeling. METHODS: A 16-month-old boy, who underwent palatoplasty for cleft palate at Chungnam National University Hospital when he was 12 months old of age, visited St. Mary's Hospital for known DiGeorge syndrome with craniosynostosis. He had growth retardation and was also diagnosed with hydronephrosis and thymic agenesis. His chromosomal study showed microdeletion of 22q11.2. On physical examination, there were parieto-occipital protrusion and bifrontotemporal narrowing. The facial bone computed tomography showed premature closure of metopic suture, orbital harlequin sign and decreased anterior cranial volume. The interorbital distance was decreased(17mm) and the cephalic index was 93%. RESULTS: After the correction of metopic synostosis by anterior 2/3 calvarial remodeling, the anterior cranial volume expanded with increased interorbital distance and decreased cephalic index. Fever and pancytopenia were noted at 1 month after the operation, and he was diagnosed as hemophagocytic lymphohistiocytosis by bone marrow study. He however, recovered after pediatric treatment. There was no other complication during the 12 month follow up period. CONCLUSION: This case presents with a rare combination of DiGeorge syndrome and metopic synostosis. When a child is diagnosed with DiGeorge syndrome soon after the birth, clinicians should keep in mind the possibility of an accompanying craniosynostosis. Other possible comorbidities should also be evaluated before the correction of craniosynostosis in patients as DiGeorge syndrome. In addition, postoperative management requires a thorough follow up by a multidisciplinary team of plastic surgeons, neurosurgeons, ophthalmologists and pediatricians.

The Endocrine Manifestations and Growth of the Patients with 22q11.2 Microdeletion Syndrome / 대한소아내분비학회지

PURPOSE:Varying clinical phenotypes are associated with the chromosome 22q11.2 microdeletion syndrome. The endocrine manifestation are latent or overt hypoparathyroidism, thyroid dysfunction and short stature. This study was undertaken to investigate frequencies of endocrine abnormalities and short stature in patients with the chromosome 22q11.2 microdeletion syndrome. METHODS:Forty three unrelated patients were diagnosed having chromosome 22q11.2 microdeletion syndrome. Chromosomal microdeletion was confirmed by fluorescent in situ hybridation (FISH) with DNA probe (22q11.2 LSI TUPLE1 from Vysis). Serum total calcium and intact parathyroid hormone (PTH) were measured in all patients. Thyroid function tests including free thyroxine(T4), thyroid stimulating hormone (TSH) and thyroid autoantibodies were performed in all patients. Insulin-like growth factor-1 (IGF-1) was measured in 10 patients. Height, weight and body mass index were compared with chronological age in all patients. RESULTS:Seven patients (16%) had an overt hypoparathyroidism, presenting with hypocalcemic tetany. Thirteen patients (31%) showing hypocalcemia with normal PTH were regarded as having latent hypoparathyroidism since their PTH secretion response was blunted. Out of 2 patients with thyroid diseases, one patient had Graves disease and the other had Hashimoto thyroiditis. Five patients (12%) were below the 3rd percentile in height at evaluation. The BMI was below the 5th percentile in 23% of patients. CONCLUSION: Twenty patients (47%) presented with overt and latent hypoparathyroidism. Interestingly, autoimmune thyroid diseases such as Graves disease and Hashimoto thyroiditis were associated in patients with chromosome 22q11.2 microdeletion, indicating predisposition to autoimmune disorders. Therefore, a careful endocrine and growth evaluation is needed in these patients.

A rapid method for molecular diagnosis of 22q11.2 microdeletion syndrome / 第二军医大学学报

Objective:To explore a rapid, economical and efficient approach for molecular detection of 22q11.2 micro-deletion syndrome. Methods: Fifty ventricular septal defect (VSD) patients (33 males and 17 females, age ranged from 1 month to 15 years), who were hospitalized in Nanjing Children's Hospital from Jan. 2004 to Jan. 2005, were randomly selected for this study. The peripheral blood of VSD patients and the buckle cells of their parents were obtained. Three short tandem-repeat polymorphism (STRP) markers, D22S944, 22D_4_2 and 22D_4_3, were used for fluorescent in situ hybridization(FISH)study and genotype analysis. Results: 22D_4_2 and 22D_4_3 produced clear electrophoresis band, and the detections were rapid and efficient. The 3 STRP markers were consistent with the Hardy-Weinberg equilibrium expectations, and their heterozygosity was high in the present population from Chinese Han nationality in Jiangsu province. FISH confirmed that 5 of the 50 VSD patients had a deletion within chromosome 22q11.2. Conclusion: Three STRP markers (D22S944, 22D_4_2 and 22D_4_3) (analysis) combined with FISH as a supplementary is an efficient and reliable approach for detection of (22q11.2 microdeletion.)