Evaluation of clinical and laboratory findings of patients with williamssyndrome

Introduction – Objective: The mutations that cause genetic diseases are evaluated under 3 main headings as genome mutation, chromosome mutation and gene mutation. Microdeletion syndromes are submicroscopic chromosomal part ruptures that are too small to be detected by chromosome analysis. Among the microdeletion syndromes that can be categorized by the effected area of the chromosome, Williams, velocardiofacial, Prader-Willi, Angelman syndromes are the best known ones. William syndrome (WS) occurs as a result of microdeletion at the localization 7q11.23 of the chromosome. Williams syndrome is characterized by; typical facial appearance (elf face), cardiovascular disease (supravalvular aortic stenosis (SVAS), peripheral pulmonary stenosis (PPS), hypertension (HT), short stature, growth retardation, mental retardation (MR), endocrine disorders (hypercalcemia, hypercalciuria, hypothyroidism, early puberty) connective tissue diseases and an unique personality also called cocktail type In patients, many systems that may cause significant mortality and morbidity are effected as a result of multiple gene losses. The aim of the study is the discussion of the clinical course of the disease by identifying anthropometric measurements, phenotypic features (short stature, microcephaly, temporal stenosis, hypertelorism, nasal root hoarseness, big ear, epicantal fold, prominent nose, malar hypoplasia, long filtrum, coarse voice, plump cheeks, clinodactyly, nail hypoplasia, etc.), dental anomalies(malocclusion, adonti, microdontics), eye anomalies(strabismus, hyperopia, star appearance in the iris, etc.), and accompanying additional diseases (cardiac anomalies, hypothyroid, celiac disease, renal anomaly, early puberty etc.) in patients with WS, diagnosed with clinical findings and confirmed by FISH analysis. In addition, due to the hypercalcemia defined in patients with WS, patients can be directed to calcium-poor diet and vitamin D restriction even in the period that they are normocalcemic. In our study, whether calcium-containing foods were avoided in order to evaluate bone mineral metabolism of our patients, duration of vitamin D use, daily sun exposure, exercise / walking frequency were recorded and serum calcium, phosphorus, alkaline phosphatase, dual energy x-ray (which were made to evaluate the 25- hydroxy vitamin D [25(OH)D] levels and bone metabolism) absorptiometry [(DEXA) femur-vertebra] results are aimed to be examined. Materials and Methods: A total of 42 patients, including 19 girls and 23 boys diagnosed as WS, who were followed up by Akdeniz University Faculty of Medicine, Department of Child Health and Diseases and Child Genetic Science between 2004-2019, were included in the study. The study was approved by Akdeniz University Non-Interventional Clinical Research Ethics Committee. Criteria for inclusion in the study was determined as; 1) To be compatible with WS clinical diagnosis, 2) No other etiology was shown for the clinical findings in the patient, 3) The diagnosis was confirmed by FISH analysis. Exclusion criteria from the study determined as; 1) Patients with unconfirmed diagnosis of WS, 2) Patients who were off the regular follow-up. Clinical and laboratory values of patients' phenotypic features, anthropometric measurements, concomitant cardiovascular system, endocrine system, urinary system, gastroenterological system, musculoskeletal system evaluation and bone metabolism were recorded from the registration file information. In addition, the BMD (Bone Mineral Density) data of 20 patients, 12 male and 8 female, were evaluated. Findings: When the cardiovascular characteristics of the patients in the study group were examined, supravalvular aortic stenosis in 33.3%, peripheral pulmonary stenosis in 21.4%, VSD in 19.0%, mitral valve diseases in 14.3%, hypertension in 11.9%, aortic failure in 9.5%, ASD in 7.1% and aortic coarctation in 7.1% was observed. In the urinary system evaluation of the patients, renal agenesis was detected in 4 patients (9.5%), nephrocalcinosis in 3 patients (7.1%), and VUR in 2 patients (4.8%). When the endocrine system evaluation of the patients were examined, hypothyroidism in 9 patients (21.4%), hypercalcemia in 7 patients (16.6%), growth hormone (GH) deficiency in 2 patients (4.7%), and puberty precox in 2 patients (4.7%) had been determined. In the gastrointestinal system examination, 40.7% of patients had recurrent abdominal pain, while 21.4% had constipation, 19.0% had GER and 4.9% had celiac disease. Considering the dental features of patients, malocclusion in 25 patients (n = 25/42, 59.5%), enemal hypoplasia in 21 patients (n= 21/42, 50%), microdontia in 15 patients (n= 15/42, 35%, 7) and adontias in 7 patients (n= 7/42, 16.7%) were found. In the eye evaluation of the patients, star iris in 23 patients (n= 23/42, 54.8%), strabismus in 13 patients (n= 13/42, 31%), hyperopia in 5 patients (n= 5/42, 11.9%) and myopia features were observed in 4 patients (n= 4/42, 9.5%). Of the musculoskeletal features, the number of patients with hypermobility 17 (n= 17/42, 40.5%), the number of patients with scoliosis 11 (n= 11/42, 26.2%), the number of patients with kyphosis 4 (n= 4/42 (9.5%) and the number of patients with contractures was 3 (n= 3/42, 7.1%). In the evaluation of bone metabolism of all patients being followed-up, serum calcium values ranged from 9.10 mg/dl to 10.90 mg/dl (avg.10,06 ± 0,51), phosphorus values ranged between 1.90 and 6.10 (avg. 4,76 ± 0,96), and vitamin D value ranged between 6.50 and 41.60 (avg. 20,02 ± 6,72). While the PTH level of the patients was changing between 13.05 pg/ml and 143 pg/ml (avg. 49.85 ± 26.58), the ALP levels were between 53 UI/L and 459 UI/L (avg.152.20 ± 81.96). While the age distribution of patients with BMD measurements ranged from 4 to 18 years (avg. 11.45 ± 4.93), their height varies between 6 cm and 174 cm (avg. 133.65 ± 26.24) and Z-score according to height was between -3.56 and 0.72 (avg. -1.24 ± 0.96). When BMD was evaluated, for lumbar vertebrae, the results were between -3.8 and 2.0 (-0.5 ± 1.3), after correction of these results by height, it was found to be varied between -3.06 to 2.64 (avg.0.16 ± 1, 34). When the BMD results for the femoral neck are examined, results between -3.86 and 0.4 (avg. -1.31 ± 1.09) were obtained, and when these results are adjusted according to the height, results between -2.77 and 1.03 (avg. -0.84 ± 1.05) were obtained. While the bone mineral density (BMD) for lumbal vertebra was low in 5 (%25) patients, it was low in 3 (15%) patients when BMD were calculated for lumbal vertebra adjusted to height, it was low on 14 (70%) patients when BMD was examined for femoral neck of patients and lastly it was low on 9 (45%) patients when BMD adjusted to height was calculated. Results: With our study, it is thought that we will contribute to the literature by comparing our data, which were gathered by examining the phenotypic, clinical and laboratory findings of our patients with WS, who were followed-up with a multidisciplinary approach, and who had multiple system evaluations, with national and international studies. In addition to the clinical and laboratory findings described so far in patients with WS in childhood, the data on BMD in the Turkish population were evaluated first. There are also rare studies on the subject in the literature. As a result of our findings, it is clear that new and further studies are needed to increase the number of cases. In conclusion, we can offer effective genetic counseling and clinical monitoring to patients with WS based on our data. In this way, early diagnosis of complications that can accompany the disease, taking appropriate measures with proper management will increase the quality of life.