Ferda Özkınay

Objective: Achondroplasia is an autosomal dominant genetic disorder, characterised by distinctive growth patterns and recognisable skeletal features. This study aimed to determine the demographic and clinical characteristics, quality of life (QoL) losses, and expectations of individuals with achondroplasia in Türkiye. Design: In this survey‐based study, Computer‐Assisted Telephone Interviewing (CATI) system was used and questions were directed to patients or their parents via phone calls. Patients: A total of 140 patients with achondroplasia, of whom 50.7% were male (age range, 0–20 years) were included. Measurements: The questionnaire forms were prepared by a committee including clinicians and the president of the Achondroplasia and Families Association. The forms included questions on sociodemographic characteristics, diagnosis and treatment, expectations from the patient association, and quality of life. Results: Achondroplasia was commonly diagnosed by obstetricians (76.5%) and the patients were followed by multiple specialties. Of the patients, 10% received growth hormone treatment, and 55.7% underwent at least one surgical procedure, with 23.6% undergoing limb lengthening surgery. The main symptoms frequently/very frequently observed in the patients were: sleep‐disordered breathing (40%), recurrent ear infections (32%), and frequent respiratory tract infections (28%). The primary concerns involved experiences of social exclusion due to physical appearance and together with related psychological challenges. The main expectations of the participants and parents from the association were to receive education on achondroplasia management and new treatment options, and to promote public awareness. Conclusions: Patients with achondroplasia face significant challenges in daily life, they require medical treatment and some supportive services to improve their quality of life.

Background Homozygous mutations in the Caspase-associated recruitment domain 9 (CARD9) gene increase susceptibility to invasive fungal infections, particularly those caused by Candida species. This study aims to assess the spectrum of CARD9 gene mutations that predispose individuals in the Turkish population, especially children, to invasive fungal infections. Methods Our study included 30 patients who were admitted to Ege University due to invasive fungal infection or chronic mucocutaneous candidiasis between 2020 and 2023. Demographic and clinical data of the patients were recorded, and a sequence analysis of the CARD9 gene was performed. Results The median age of the patients was 1.8 years (interquartile range [IQR]: 11.8). Diagnoses included fungal endocarditis (n = 8, 26.6%), chronic mucocutaneous candidiasis (n = 7,23.3%), central nervous system (CNS) infections (n = 6,20%), candidemia (n = 4,13.3%), fungus ball in the kidney (n = 2, 6.7%), endophthalmitis ( n = 1, 3.3%), concurrent CNS and intra-abdominal infection (n = 1, 3.3%), and concurrent CNS infection and endophthalmitis (n = 1, 3.3%). All 12 exons and exon–intron junctions of the CARD9 (NM_052813.5) gene that encodes the CARD9 protein were analyzed. A disease-causing variant was detected in 2 patients (6.6%). One patient had a Pseudallescheria boydii brain abscess, and the other had an invasive fungal infection confirmed histopathologically. Conclusions Among the 30 patients with invasive fungal infections, a disease-causing CARD9 mutation was identified in 2 (6.6%) patients. While CARD9 mutations are known to be associated with invasive candidiasis, this study reports the first pediatric case of P. boydii infection associated with a CARD9 mutation.

Amaç: Embriyo implantasyonu ve plasental dolaşımın temel sorumlusu olan kapiller damarlardaki patolojilerin abortus etiyolojisindeki mekanizmalar üzerinde etkileri olduğu bilinmektedir. Matriks metalloproteinaz (MMP) ailesinden MMP2 ve MMP9’un ekstrasellüler matriks organizasyonunda ve trofoblast implantasyonunda önemli görevleri vardır. Bu çalışmada, fonksiyonel olduğu bilinen MMP2 -735 C>T, -1306 C>T ve MMP9 -1562 C>T polimorfizmlerinin spontan abortus (SA) materyallerindeki genotip farklılıklarını belirlemek ve bu polimorfizmlerin SA etiyolojisinde rolü olup olmadığına ışık tutabilmek amaçlanmıştır. Gereç ve Yöntem: Polimorfizmlerin genotiplerinin analizinde restriksiyon fragman uzunluk polimorfizmi (RFLP) yöntemi kullanılmıştır. Çalışma grubu 80 spontan abortus örneğinden, kontrol grubu 100 sağlıklı gönüllü bireyin periferik kan örneğinden oluşmaktadır. Bulgular: MMP2 -735 C>T ve MMP9 -1562 C>T polimorfizmleri için SA örnekleri ve kontrol grubu arasında anlamlı fark saptanmadı. MMP2 -1306 C>T polimorfizminin heterozigot genotip sıklığı SA örneklerinde kontrol grubuna kıyasla 2,2 kat daha fazla bulundu (p=0.043). MMP2 genindeki normal -735 C>T ve heterozigot -1306 C>T genotiplerinin birlikte görülme sıklığı SA örneklerinde kontrol grubuna göre 3,7 kat fazla idi (p=0.021). Sonuç: MMP2 -1306 C>T fonksiyonel polimorfizmi ile SA oluşması arasında bir ilişki bulunmuştur. Daha yüksek sayılardaki SA çalışmalarındaki ileri genetik çalışmalar ve ekspresyon analizleri MMP2 ve MMP9 polimorfizmlerinin SA üzerindeki potansiyel rollerini net olarak belirlemede katkıda bulunacaktır.

Objective: Osteogenesis imperfecta (OI) consists of a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. The aim was to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients using targeted next-generation sequencing (NGS). Methods: A targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform in patients with a confirmed diagnosis of OI. Results: Fifty-six patients (female/male: 25/31) from 46 different families were included. Consanguinity was noted in 15 (32.6%) families. Based on Sillence classification 18 (33.1%) were type 1 OI, 1 (1.7%) type 2, 26 (46.4%) type 3 and 11 (19.6%) type 4. Median body weight was -1.1 (-6.8, - 2.5) standard deviation scores (SDS), and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity affected 30 dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes ( FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected by NGS panel had not previously been reported and were also classified as pathogenic based on American College of Medical Genetics guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in any of the 13 OI genes on the panel. Conclusion: Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. Furthermore, nine new variants were identified in known OI genes which were classified as pathogenic by standard guidelines.

Objectives: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next‐generation sequencing (NGS) and clinical‐exome‐based copy number variant (CNV) analysis in patients with CHA.Methods: One hundred and forty‐three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole‐exome sequencing in nine patients. Exome‐based CNV calling was incorporated into the traditional single‐nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long‐range polymerase chain reaction.Results: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR.Conclusions: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.

The post-COVID-19 syndrome is a new syndrome defined in patients with a history of probable or confirmed SARS-CoV-2 infection, usually within three months of the onset of COVID-19, with symptoms and effects lasting at least 2 months. This study is aimed at comprehensively comparing symptoms of the post-COVID-19 syndrome in children with Delta and Omicron variants. This prospective study included children with COVID-19 followed in hospitalized or outpatient clinics in a tertiary hospital. We used a special questionnaire to ask about the presence of persistent symptoms more than 12 weeks after the initial diagnosis. Patients with positive SARS-CoV-2 PCR were selected randomly and grouped according to the dominant variants in our country at that time as follows: Omicron group (after December 16, 2021); Delta (B.1.617.2) group (August 15, 2021, and December 15, 2021). This study included 200 children, 71 of whom were in the Delta group and 129 of whom were in the Omicron group. Weakness (8.5% vs. 1.6%; p = 0.017), the impact of physical efforts (5.6% vs. 3.9%; p = 0.020), fatigue (22.5% vs. 8.5%; p = 0.009), anxiety disorder (12.7% vs. 0.8%; p = 0.001), and gastrointestinal changes (12.7% vs. 4.7%, p = 0.050) were statistically significantly higher in patients with the Delta variant compared to patients with the Omicron variant. There were no differences between the groups regarding anorexia, anosmia/ageusia, arthralgia, influenza-like symptoms, sleeping disorders, decreased physical activity daily, headache, need for analgesia, concentration and memory disorder, and weight loss (p > 0.05).   Conclusion: This study showed that weakness, the impact of physical efforts, fatigue, anxiety disorder, and gastrointestinal changes were more frequent in the Delta group compared to the Omicron group. The incidence of post-COVID-19 syndrome is high in children as well as adults and affects several systems; therefore, it should be kept in mind that children should be followed for post-COVID-19 syndrome. What is Known: • Despite the milder severity of acute COVID-19 in children, post-COVID-19 symptoms may occur. The post-COVID-19 condition is complex and novel, especially in the pediatric population. What is New: • Post-COVID-19 symptoms in children differ depending on the viral variant. Post-COVID-19 syndrome has a great impact on the social life of children which may have serious and long-term effects.

Koolen‐de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.31 deletion, and report on several rare/new conditions. Eight patients from unrelated families aged between 17 months and 19 years enrolled in this study. All patients evaluated by a clinical geneticist, and the clinical diagnosis were confirmed by molecular karyotyping. KdVS patients had some common distinctive facial features. All patients had neuromotor retardation, and speech and language delay. Epilepsy, structural brain anomalies, ocular, ectodermal, and musculoskeletal findings, and friendly personality were remarkable in more than half of the patients. Hypertension, hypothyroidism, celiac disease, and postaxial polydactyly were among the rare/new conditions. Our study contributes to the clinical spectrum of patients with KdVS, while also provide a review by comparing them with previous cohort studies.

Multisystem Inflammatory Syndrome (MIS-C) is a new entity that emerges 2–4 weeks after the SARS-CoV-2 infection in children. MIS-C can affect all systems, the most severe of which is cardiac involvement. The duration of the cardiac symptoms is still uncertain and may be persistent or prolonged. The American College of Rheumatology Clinical Guidelines recommends cardiac magnetic resonance imaging (MRI) 2–6 months after the diagnosis of MIS-C in patients presenting with significant transient left ventricular (LV) dysfunction in the acute phase of illness (LV ejection fraction 50%) or persistent LV dysfunction. There are a few studies investigating cardiac MRI findings in MIS-C patients. In this study, we aimed to evaluate cardiac MRI findings, at the earliest 3 months after diagnosis, and compare these findings with the echocardiograms in children with MIS-C. A retrospective study including 34 MIS-C patients was conducted at a tertiary-level University Hospital between June 2020 and July 2021. Centers for Disease Control and Prevention criteria were used in the diagnosis of MIS-C. Cardiac MRI was performed at least 3 months after MIS-C diagnosis. The study included 17 (50%) boys and 17 (50%) girls with a mean age of 9.31 ± 4.72 years. Initial echocardiographic evaluation revealed cardiac abnormality in 13 (38.2) patients; 4 (11.8%) pericardial effusion, 4 (11.8%) left ventricular ejection fraction (LVEF) < 55%, and 5 (14.7%) coronary artery dilatation. Echocardiography showed normal LV systolic function in all patients during follow-up; coronary dilatation persisted in 2 of 5 (40%) patients at the 6th-month visit. Cardiac MRI was performed in 31 (91.2%) patients, and myocardial hyperemia was not detected in any patients (T1 relaxation time was < 1044 ms in all children). However, 9 (29%) patients’ MRI showed isolated elevated T2 levels, and 19 (61.3%) revealed at least one of the following findings: pericardial effusion, right ventricular dysfunction, or LVEF abnormality. In patients with MIS-C, a high rate of cardiac involvement, particularly pericardial effusion was determined by cardiac MRI performed at the earliest 2–6 months after diagnosis. Even if echocardiography does not reveal any abnormality in the initial phase, cardiac MRI should be suggested in MIS-C patients in the late period. This is the first study reporting cardiac MRI findings in the late period of MIS-C patients.