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Objective: Congenital heart defects occur in approximately 50% of children with Down syndrome and they contribute considerably to morbidity and mortality. The aim of this study is to investigate the prevalence, classification, and survival of congenital heart defects in Down syndrome. Materials and Methods: About 1731 Down syndrome patients who underwent echocardiography between 1986 and 2022 were evaluated. The median follow-up duration was 8.7 years (range 1-35.8 years). Congenital heart defect was grouped as cyanotic and acyanotic. Results : Among the 1731 patients, 52.1% had congenital heart defects. Congenital heart defect was significantly more common in females than males. The most common cardiac defect was ventricular septal defect (35%), followed by atrial septal defect (31.8%), atrioventricular septal defect (23.4%), tetralogy of Fallot (5%), and patent ductus arteriosus (3.6%). In the follow-up, 43.2% of atrial septal defect, 17.8% of ventricular septal defect, and a total of 20% of congenital heart defects were closed spontaneously. About 34.4% of congenital heart defect was corrected by cardiac surgery/intervention. Five-year survival rate was 97.4% in patients without congenital heart defects, whereas it was 95.6% in mild congenital heart defects and 86.1% in moderate to severe congenital heart defects. There was no relationship between consanguinity, parental age, maternal disease, folic acid supplementation before/during pregnancy, gestational age, birth weight, and congenital heart defects. Neuromotor development was similar in patients with and without congenital heart defects. Conclusion: We demonstrated that almost half of the patients had congenital heart defects; ventricular septal defect was the most common congenital heart defect type. This study is valuable in terms of the largest single-center study describing the classification, prognostic factors, and survival of Down syndrome patients with congenital heart defect from Turkey.

Overgrowth-intellectual disability (OGID) syndromes are clinically and genetically heterogeneous group of disorders. The aim of this study was to examine the molecular etiology and long-term follow-up findings of Turkish OGID cohort. Thirty-five children with OGID were included in the study. Single gene sequencing, clinical exome analysis, chromosomal microarray analysis and whole exome sequencing were performed. Five pathogenic copy number variants were detected in the patients; three of them located on chromosome 5q35.2 (encompassing NSD1), others on 9q22.3 and 22q13.31. In 19 of 35 patients; we identified pathogenic variants in OGID genes associated with epigenetic regulation, NSD1 (n = 15), HIST1H1E (n = 1), SETD1B(n = 1), and SUZ12 (n = 2). The pathogenic variants in PIK3CA (n = 2), ABCC9 (n = 1), GPC4 (n = 2), FIBP (n = 1), and TMEM94 (n = 1) which had a role in other growth pathways were detected in seven patients. The diagnostic yield was 31/35(88%).Twelve pathogenic variants were novel. The common facial feature of the patients was prominent forehead. The patients with Sotos syndrome were observed to have milder intellectual disability than patients with other OGID syndromes. In conclusion, this study showed, for the first time, that biallelic variants of SUZ12 caused Imagawa-Matsumoto syndrome, monoallelic variants in SETDIB resulted in OGID. Besides expanded the phenotypes of very rare OGID syndromes caused by FIBP and TMEM94.

Objective: Trichorhinophalangeal syndrome is a rare autosomal dominant disorder characterized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II. Materials and Methods: A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhinophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses. Results : A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1 - EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophalangeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophalangeal syndrome II, although microdeletion sizes and facial or skeletal features were not correlated, patients with larger deletions had severe intellectual disability. Conclusion: This study has expanded the existing knowledge on the phenotype–genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.