Application Of Cytogenetic And Molecular Cytogenetic Evaluation Methods In 271 Short Stature Patients

Background: Short stature is defined as a height that is more than 2 SDs or 3rd percentile(1.88D) below the mean for age, sex, and corresponding population, within the similar living conditions. Multifarious causes and the wide range of differential diagnosis make it hard to give a specific diagnose which means multiple evaluation methods need to be equipped. However, due to the incomplete application of diverse testing methods for short stature, the relevant development and researches slow down. Finally, patients who suffer from short stature cannot receive clear diagnose or effective treatment. Objective: This study aimed to retrospectively analyze the data collected from short stature patients who referred to the Genetics lab(Oklahoma University Health Sciences Center, OUHSC) for genetics evaluation such as cytogenetics and molecular cytogenetics methods. Thus to emphasize the importance of genetics assessment method in the diagnosis of short stature. And furthermore to supplement the deficient research data in this field in China, and provide references for further scientific research and clinical application.Methods: The method is to analyze tests results acquired from 271 specimens clinically diagnosed as short stature with or without other symptoms referred to OUHCS genetics lab from 2000-2013. Those specimens were tested mainly as follows, karyotype analysis, fluorescence in situ hybridization(FISH), microarray-comparative genomic hybridization(microarray-CGH) and Sanger sequencing.Results: 1. Sex ratio: 80 cases out of 271 were male(29.52%) including 17 abnormal cases(21.25%) and 191 cases out of 271 were female(70.48%) including 43 abnormal ones(22.51%). There is no statistically significant difference between the prevalence rates of male and female(χ2=0.052,P=0.478).2. Age: The range of age admitted to lab was 0~32 year old and median age was 7.74 ± 5.50 years old. 3. Initial triage or treatment departments of hospital: Department of Pediatrics genetics or Genetics 116 cases, Department of Endocrinology 114 cases, normal outpatient department of Pediatrics 24 cases, Pediatrics inpatient 13 cases, Department of Neonatology 2 cases, Department of Rheumatism 1 case, Department of hematology 1 case. 4. A total of 271 specimens took 432 trials, 60 specimens were positive by 83 trials including 29 anomalies out of 235 Karyotype analyses, 20 anomalies out of 67 fluorescence in situ hybridization, 30 anomalies out of 83 microarray-CGH, 2 anomalies out of 2 SNP-array trials, 2 anomalies out of 15 Sanger Gene sequencing. 5. In the 60 positives cases, 16 were diagnosed as Turner syndrome or Turner syndrome changes. 5 cases were diagnosed as other diseases that cause short stature. The clinical diagnosis and significance were not clear in 37 cases according to today knowledge. 2 cases were diagnosed as of normal variants.Conclusion: 1. Genetics evaluation methods such as cytogenetics and molecular cytogenetics assessment should be widely used in the diagnosis of short stature if the clinical evidences support the application of genetics tests. 2. It is of great importance to select the appropriate testing methods for patients with short stature, and achieve reasonable utilization of experimental resources optimally. 3. The etiology of short stature is complex and the treatment takes long, thus, early diagnosis shows great significance for prognosis.