Genetic findings in short Turkish children born to consanguineous parents

IntroductionThe diagnostic yield of genetic analysis in the evaluation of children with short stature depends onassociated clinical characteristics, but the additional effect of parental consanguinity has not beenwell documented.MethodsThis observational case series of 42 short children from 34 consanguineous families was collected bysix referral centres of paediatric endocrinology (inclusion criteria: short stature and parentalconsanguinity). In eighteen patients (12 families, Group 1), the clinical features suggested a specificgenetic defect in the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, and a candidategene approach was used. In others (Group 2) a hypothesis-free approach was chosen (gene panels,microarray analysis, and whole-exome sequencing), further subdivided into 11 patients with severeshort stature (height <-3.5 SDS) and microcephaly (head circumference <-3.0 SDS) (group 2a), 10patients with syndromic short stature (group 2b) and were 3 patients with nonspecific isolated GHdeficiency (group 2c).ResultsIn all 12 families from group 1, (likely) pathogenic variants were identified in GHR, IGFALS, GH1, andSTAT5B. In 9/12 families from group 2a, variants were detected in PCNT, SMARCAL1, SRCAP, WDR4and GHSR. In 5/9 families from group 2b, variants were found in TTC37, SCUBE3, NSD2, RABGAP1,and 17p13.3 microdeletions. In group 2c no genetic cause was found. Homozygous, compoundheterozygous and heterozygous variants were found in 21, 1 and 4 patients, respectively.ConclusionGenetic testing in short children from consanguineous parents has a high diagnostic yield, especiallyin cases of severe GH deficiency or insensitivity, microcephaly, and syndromic short stature

Volume CXIV, Number 4, November 7, 1996

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespa

The Relation of Complete Blood Count Parameters with Metabolic and Clinical Parameters in Overweight and Obese Children

Aim: This study aims to assess white blood cell count, platelet count, and platelet indices as a metabolic indicator in overweight, obese and morbidly obese children

Assessment of pulmonary function by impulse oscillometry and spirometry in children with type 1 diabetes mellitus

Aim To assess the lung functions with impulse oscillometry (IOS) and spirometry in children with type 1 diabetes mellitus (T1DM). Methods Fifty-one children with T1DM, and sex- and age-matched 53 healthy control (HC) subjects were included in this study. Demographic, clinical, and laboratory characteristics of the subjects were recorded and their pulmonary functions were analyzed by IOS and spirometry. Results In IOS, zR5, zR10, and zR20 levels were higher in children with T1DM compared with HCs (P = .019,P = .017, andP = .002, respectively). In spirometry, zFEF75 and zFEF25-75 were lower in children with T1DM compared with HCs (P = .025,P = .001, respectively). In IOS, zR5-20 (P = .008,P = .005, respectively) and zAX (P = .013,P = .009, respectively) were significantly lower in good-controlled group compared with moderate- and poor-controlled group. In spirometry, zFEF25-75 was significantly higher in good-controlled group compared with moderate- and poor-controlled group (P = .005,P = .009, respectively). HbA1c was positively correlated with zR5-20 value (r = .339;P = .017) in male children with T1DM. The duration of the disease was positively correlated with zR5-20 (r = .290;P = .043) and zFres (r = .358;P = .010). According to the receiver operating characteristic curve analysis to estimate optimal cut-offs to discriminate good control level of T1DM (HbA1c < 7%), a zR5-20 <= 2.28 demonstrated a 75.0% sensitivity and 82.9% specificity, with an area under the curve of 0.805 ([confidence interval, 0.615-0.995];P = .007). Conclusions This study showed subclinical impairment of lung functions which is associated with disease duration and the degree of metabolic control in children with T1DM

Etiological Evaluation of Congenital Hypothyroidism Cases

Objective: The aim of this study was to determine, (i) the cause of congenital hypothyroidism (permanent or transient), (ii) the etiological cause of persistent congenital hypothyroidism and (iii) to investigate the role of clinical and laboratory data in predicting persistent and transient congenital hypothyroidism

Iodine status of pregnant women in a metropolitan city which proved to be an iodine-sufficient area. Is mandatory salt iodisation enough for pregnant women?

The objective of this study was to assess the iodine status of pregnant women in a metropolitan city which was stated as iodine sufficient area after salt iodination program. This multicenter, cross-sectional study was carried out on 3543 pregnant women. Age, gestational weeks, smoking, consumption of iodized salt, dietary salt restriction, history of stillbirth, abortus and congenital malformations were questioned. Spot urine samples were analyzed for urine iodine concentration (UIC). The outcomes were: (a) median UIC in three trimesters of pregnancy and (b) frequency of ID among pregnant women. The median UIC was 73 mu g/L. The median UIC was 77 mu g/L (1-324), 73 mu g/L (1-600) and 70 mu g/L (1-1650) in three trimesters of pregnancy, respectively (p: 0.14). UIC < 50 mu g/L was observed in 36.6% (n: 1295) and UIC < 150 mu g/L was observed in 90.7% (n: 3214) of pregnant women. Only 1% (n: 34) of the pregnant women had UIC levels higher than 500 mu g/L. This study showed that more than 90% of the pregnant women in this iodine-sufficient city are facing some degree of iodine deficiency during their pregnancy. A salt iodization program might be satisfactory for the non-pregnant population, but it seems to be insufficient for the pregnant population