ESPE Abstracts (2018) 89 P-P2-016

The Spectrum of Genetic Defects in Congenital Adrenal Hyperplasia in the Population of Cyprus: A Retrospective Analysis

Nicos Skordisa,b,c, Pavlos Fanisb, Meropi Toumbad,b, Charilaos Stylianoue, Michalis Picolosf, Elena Andreoug, Andreas Kyriakouh, Lambrini Yiannakide-Mylie, Michalis Iasonidesi, Stella Nicolaoue, Tassos C Kyriakidesj, George A Tantelesk, Vassos Neocleousb & Leonidas A Phylactoub,l


aSt George’s, University of London Medical School at the University of Nicosia, Nicosia, Cyprus; bDepartment of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; cDivision of Pediatric Endocrinology, Paedi Center for specialized Pediatrics, Nicosia, Cyprus; dPediatric Endocrine Clinic, IASIS Hospital, Paphos, Cyprus; eDivision of Pediatric Endocrinology, Makarios III Hospital, Nicosia, Cyprus; fAlithias Endocrinology Center, Nicosia, Cyprus; gDasoupolis Endocrinology Center, Nicosia, Cyprus; hDevelopmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, UK; iIliaktida Peadiatric & Adolescent Medical Centre, Limassol, Cyprus; jYale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, USA; kDepartment of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; lCyprus School of Molecular Medicine, Nicosia, Cyprus


Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is worldwide the most common autosomal recessive disorder caused by defects in the CYP21A2 gene.

Objective: The main objective of the study was to evaluate CAH in Cyprus over a 10 year period.

Methods: All known patients were included in a population retrospective subset analysis of Cypriot patients with confirmed CAH and their clinical severity, genotype and sex were evaluated.

Results: Our data, is an extensive description of the diverse clinical forms of CAH over time. From 2007 to 2017, one hundred and twenty one patients with various degrees of CAH were categorized and genotyped at the Molecular Genetics, Function and Therapy department of the Cyprus Institute of Neurology and Genetics. We identified 121 patients with various degrees of the disorder and were categorized in 4 mutation groups (null, A, B and C) based on their clinical and biochemical findings. The majority of patients (85.12%) belonged to the non-classic (NC)-CAH form and the disorder was more often diagnosed in females (61.1%) who exhibited various degrees of hyperandrogenemia. The most severe classic salt-wasting (SW) form was identified in 11 neonates (9.1%). Seven (5.8%) children were also identified with the simple virilising (SV) form and a median presentation age of 5 yrs (interquartile range (IQR) 3.2–6.5). In the 242 nonrelated alleles, the most frequent mutation was found to be p.Val281Leu (59.5%) followed by IVS2-13A/C>G (9.1%), DelEx1-3 (6.2%), p.Val304Met (4.6%) and p.Gln318stop (4.1%). A series of other less frequent mutations including rare deletions were also identified. With an estimated population of 701,000 Greek Cypriots (Cyprus statistical service 2016) the prevalence of CAH is estimated to be around 1.7 cases per 10000 people. Based on the recent study by our group where the true carrier frequency of CYP21A2 gene was reported to be 1:10, the identified CAH patients in the Greek Cypriot population are about the 6.9% of the ones estimated to exist in the Greek Cypriot population.

Conclusion: Overall, the compiled data of the present work from a coherent population could help physicians in both the treatment and genetic counselling of families affected with 21-hydroxylase deficiency.