Prenatal veya Postnatal Dönemde Saptanan Orofasiyal Yarıklanma Defektlerinde Tanısal Dağılım ve Genetik Etiyoloji

Abstract

Bilgic I Hacettepe University, Diagnostic distribution and genetic etiology of orofacial cleft defects detected during prenatal or postnatal period Hacettepe University Faculty of Medicine, Thesis in Pediatrics. Ankara, 2019. Orofacial clefts are one of the most common congenital anomalies. The fusion defect of structures involved in facial formation in the embryonic period is generally examined under three general groups; cleft lip, cleft palate and cleft lip and cleft palate alone, but there are other facial clefts that cannot be categorized in these groups. Orofacial cleft defects have always been a concern for patients and their family members. The aim of this study was to evaluate the clinical findings of patients with orofacial cleft defect, to determine the diagnostic distribution and to investigate the etiologic causes. The study population consisted of 520 patients who were addmitted to Hacettepe University İhsan Doğramacı Children's Hospital Department of Pediatric Genetics for the first time between September 2008 and July 2018 due to orofacial cleft defects. Among all patients, 271 patients (52.1%) were female and 249 patients (47.9%) were male. The majority of isolated cleft palates were 54.2% (n = 282), but cleft lip and palate were found in 38.8% (n = 202) cleft lip and palate, isolated lip clefts in 4.8% (n = 25) and other facial clefts were found in 2.2% (n = 11) of all patients. Gender distribution did not show a significant difference between different cleft types (p=0.514). Syndromic patients were 87.9% (n = 457) all of the patients and 12.1% (n=63) of patients were isolated (nonsndromic). Isolated cleft palate was 55.1% (n=252) of the syndromic patients, cleft lip and palate was 38% (n=174), cleft lip patients was 4.3% (n=20) of syndromic patients. Among genetic diagnoses, single gene disorders were the most common in 14% (n = 64). Microdeletion/deletion and duplication syndromes were found in 6.3% (n = 29), chromosomal anomalies in 4.4% (n = 20) and other genetic diagnoses in 17.5% (n = 80). The syndromic group which cannot be classified constitutes 57.8% (n: 264). Cardiovascular system anomalies were the most common associated anomaly and were seen in 67.2% (n=272) of the patients. Central nervous system anomalies were found in 49.4% (n=121) and vertebral anomalies in 45.2% (n=56) of all patients. Patients with cleft palate and cleft lip and palate patients had hearing loss, and it was found to be statistically significant (p=0.011). Of all patients 85.1% (n=246) had chromosome analysis, 54% (n=156) had FISH analysis, 15.6% (n=45) had microarray analysis and 1% (n=3) had whole exome sequencing. Other genetic tests were done in 10.4% (n=30) of patients. When the genetic diagnostic groups and syndromes were evaluated according to orofacial cleft types; isolated cleft palate was the most common in chromosomal anomalies %65 (=13), as it was in the microdeletion/deletion and duplication groups. Cleft palate was found in 53.1% (n=34) of monogenic syndromes, 75% (n=64) of other genetic causes and 47.3% (n = 125) of non-classified syndromes, respectively. In conclusion, a detailed, comprehensive evaluation of all children with orofacial clefts is essential. A detailed history (medical and family) and physical examination, including correct anthropometric measurements, detailed phenotype analysis, accurate evaluation of lip and palate morphology, and getting data about the consanguinity status of individuals with similar complaints are quite essential in terms of accurate and timely diagnosis and proper management.