Koray Boduroglu

Objectives: COVID-19 infection is not limited to medical aspects, but may have significant negative impacts on education, tourism, the economy as well as sociocultural, ethical, and legal aspects. We aimed to assess the multidimensional impact of the COVID-19 pandemic on pediatricians by examining their COVID-19 infection, domestic life and quarantine, as well as work patterns, educational activities, and psychosocial impact. Methods: An online survey consisted of seven sections and 68 questions was prepared through 'Google Forms.' The survey was sent via e-mail to physicians who are members of the National Pediatric Association of Turkey. Results: The pandemic has affected pediatricians working in our country in a multifaceted aspect. They experienced significant anxiety/depression/stress, 8% of them felt it at a pathological level and were receiving treatment, and women and young pediatricians were more vulnerable to the pandemic. The more adequately informed about the disease, the more prepared for COVID-19 and lower levels of psychological distress, which emphasizes the importance of education and institutional continuing support. Our study showed that academic education was seriously disrupted and the satisfaction rate with virtual education was low. Conclusion: Although COVID-19 has less impact today, it has taught us that it is necessary to be ready for new pandemics in the future. The required measures should be taken urgently and effectively healthcare professionals should follow a rational and applicable disaster plan.

Background. Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey. Methods. Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser. Results. Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years. Conclusions. HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.

Summary: Children with genetic skeletal disorders have variable conditions that can lead to sleep‐disordered breathing, and polysomnography is the gold standard for diagnosing this condition. We aimed to review polysomnography findings, to assess the severity of sleep apnea, and to investigate the clinical variables predictive of sleep‐disordered breathing in these patients. We retrospectively collected the medical records of patients with genetic skeletal disorders who underwent polysomnography for 5 years. Twenty‐seven children with various genetic skeletal disorders, including achondroplasia (14), Crouzon syndrome (3), acromesomelic dysplasia Maroteaux type (3), Apert syndrome (2), osteopetrosis (1), Jeune dysplasia (1), Desbuquois dysplasia (1), acrodysostosis (1), and spondyloepiphyseal dysplasia (1) were enrolled. The median age at the first polysomnography was 58 (1st–3rd quartile: 31–113) months. The overall sleep‐disordered breathing results were: 19 (70.3%) had obstructive sleep apneas (OSA) (4 mild, 6 moderate, 9 severe), 2 (7.4%) had central apneas, 4 (14.8%) had nocturnal hypoventilation. There was a significant correlation between non‐ambulatory status with both total AHI and OSA (p < 0.001, rho: −0.66/p = 0.04, rho: 0.38, respectively). Nine patients received positive airway pressure titration, and the oAHI values of all returned to the normal range. These patients were started with positive airway pressure treatment. Our cohort showed that the majority of the patients with skeletal dysplasia had sleep apnea syndrome characterised mainly by OSA, highlighting the importance of polysomnography screening for sleep disorders. Positive airway pressure therapy represents an effective treatment for sleep‐disordered breathing in those patients.

Primordial dwarfism (PD) is one of a highly heterogeneous group of disorders characterized by severe prenatal/postnatal growth restriction. Defects in various pathways such as DNA repair mechanism, impaired centrioles, abnormal IGF expression, and spliceosomal machinery may cause PD including Seckel syndrome, Silver–Russell syndrome. Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, II, and Meier–Gorlin syndrome. In recent years with the wide application of exome sequencing (ES) in the field of PD, new genes involved in novel pathways causing new phenotypes have been identified. Pathogenic variants in CRIPT (MIM# 604594) encoding cysteine‐rich PDZ domain‐binding protein have recently been described in patients with PD with a unique phenotype. This phenotype is characterized by prenatal/postnatal growth restriction, facial dysmorphism, ocular abnormalities, and ectodermal findings such as skin lesions with hyper/hypopigmented patchy areas and hair abnormalities. To our knowledge, only three patients with homozygous or compound heterozygous variants in CRIPT have been reported so far. Here, we report on a male patient who presented with profound prenatal/postnatal growth restriction, developmental delay, dysmorphic facial features, and skin lesions along with the findings of bicytopenia and extensive retinal pigmentation defect. A novel truncating homozygous variant c.7_8delTG; p.(Cys3Argfs*4) was detected in CRIPT with the aid of ES. With this report, we further expand the mutational and clinical spectrum of this rare entity.

Güvenoğlu M, et al. Pediatr Gastroenterol Hepatol Nutr. 2022 Nov;25(6):441-452. https://doi.org/10.5223/pghn.2022.25.6.441

Turner Syndrome (TS) is a frequently identified chromosomal disease in humans characterized by short stature, sexual infantilism, streak gonads, primary amenorrhea, and a number of somatic anomalies. Approximately 55% of TS individuals have a nonmosaic 45,X karyotype. In addition, a cell line with a Y chromosome is present in 5% of patients, which is undetectable by the standard cytogenetic analysis. The identification of Y chromatin in some TS individuals has been associated with the development of gonadoblastoma. Therefore, it is important to exclude the presence of Y chromatin in TS individuals. In this study, it was planned to detect cases with mosaicism in terms of Y chromatin with the help of Y whole chromosome probes (WCP) from individuals with TS by fluorescence in situ hybridization (FISH) analysis. Forty-four patients with Turner syndrome, who were being followed up in the Genetics Unit, were contacted and invited for the study. Of the 44 invited patients, 28 responded to the invitation. In this study, it was planned to detect TS patients with mosaicism in terms of Y chromatin with the help of the Y whole chromosome probe. The majority of the cases (71.42%) included in the study carried pure X monosomy, which is the classical Turner syndrome karyotype. Other structural X chromosome aberrations, in isolated or mosaic forms, were less frequently represented. Y chromosome sequences were searched in 28 cases with Turner syndrome by the FISH method using Y whole chromosome probe. Y chromosome sequence was detected in one (3.5%) case of 28 cases. It is recommended that individuals with Turner syndrome be screened for Y chromatin. Detection of this will provide information and guidance to individuals with Turner syndrome, especially in terms of the risk of developing gonadoblastoma, with advanced clinical consultation. This study was conducted to emphasize the importance of this.

Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated. A cohort of 23 Turkish patients with OAVS, referred to Hacettepe University Hospital, Department of Pediatric Genetics from 2008 to 2018, was included in this study. Minimal diagnostic criteria for OAVS were considered as unilateral microtia or hemifacial microsomia with preauricular skin tag. The cohort was clinically reevaluated for craniofacial and extracranial findings. Molecular etiology was investigated using candidate gene sequencing following copy number variant (CNV) analysis. WES was also performed for 2 of the selected patients. Patients in the study cohort presented similar demographic and phenotypic characteristics to previously described patients in the literature except for a higher frequency of bilaterality, cardiac findings, and intellectual disability/developmental delay. CNV analysis revealed a possible genetic etiology for 3 patients (13%). Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 (EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS. Detailed clinical evaluation for any patient with OAVS is recommended due to a high rate of accompanying systemic findings. We further expand the existing genetic heterogeneity of OAVS by identifying several CNVs and a phenotypically overlapping disorder, MFDM.

Pyloric atresia (PA) is a rare gastrointestinal anomaly that occurs either as an isolated lesion or in association with other congenital or hereditary anomalies. Familial occurrence of PA with epidermolysis bullosa (EB) has been well documented and variants in ITGA6, ITGB4, and PLEC are known to cause EB with PA. However, no gene variants have been defined in familial isolated PA. Five siblings with familial isolated PA are presented that suggest biallelic ITGB4 variants may underlie the development of PA without EB. Five siblings from two unrelated families with isolated PA were studied with exome sequencing (ES) to identify the genetic etiology in isolated familial cases. Exome sequencing was performed in one affected patient from each family. Validation and segregation studies were done by Sanger sequencing. Parents were first cousins in one family but there was no consanguinity in the other family. Type‐2 PA was detected in both families and none of the probands had associated anomalies. All patients underwent successful gastroduodenostomy and have been under follow‐up uneventfully. All patients had biallelic ITGB4 variants, c.2032G > T p.(Asp678Tyr) being a novel one. Biallelic ITGB4 variants may underlie the development of PA without associated EB. Further detection of variants in this gene may establish any possible genotype–phenotype correlations.