الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
hernia is a prevalent birth anomaly that is defined as a congenital defect in the diaphragm which allows herniation of the abdominal contents into the fetal chest and is often accompanied by other congenital anomalies predominantly varying degrees of pulmonary hypoplasia and pulmonary hypertension. It is classified into six main anatomical categories according to the location of the defect, and into two main genetic entities isolated and complex, where many patients from both classifications are attributed to an underlying genetic defect or a chromosomal aberration. CDH has been linked to over 218 genes and to various syndromes, which imply different modes of inheritance and diverse outcomes. Unclear molecular etiological mechanisms, unstandardized clinical approaches, costly and scarce diagnostic genetic services and testing to reach a definitive diagnosis and the incapacitated health system to provide sustainable multidisciplinary quality of care are the main challenges encountered during clinical diagnosis and management journey of the CDH patient.
The current study included 25 patients from 25 different families from different governorates in Egypt. Survival rate was 84% considering the study sample, with 88% of the patients diagnosed postnatally. Only 20% of the pregnant mothers in this study have been following a regular U/S examination with obstetricians while the majority (80%) were occasionally checking up when feeling unwell. Maternal age was not a factor linked to CDH as 92% of mothers were below 35 years old at time of birth of these probands. Among the various surveyed risk factors including pregnancy incidents and exposures, only anemia and previous recurrent abortions were statistically significant through this study comparing the isolated CDH patients‘ mothers and the healthy controls‘ mothers. No link or association could be made to the CDH development due to small sample size, lacking reference documents to compare and accurately analyze maternal risk factors and exposures.
Consanguinity was 32% in the families of this cohort, and only a single family had two siblings with a CDH defect and have been diagnosed with the same arterial tortuosity syndrome. Out of the 25 families (24%) reported having another sibling with another congenital anomaly and 72% reported another family member having a congenital anomaly or a congenital disease. Of the 25 patients (64%) presented at birth with other associated anomalies or conditions, which is mildly above the reported percentage for in literature of 40-50%. The most common associated congenital anomaly was CHD in 40% of the patients.
Most of these patients were Lt. side Bochdalek hernia accounting for 28%, then came Lt. side eventration and hiatal hernia in the second most prevalent types equally representing each 24% of the total number of patients. Comes next the Rt. Side Bochdalek hernia in three patients, bilateral Morgagni hernia in two patients and one case presented by Rt. side Morgagni hernia. Most of the Bochdalek hernia patients presented at the neonatal period while the rest were presenting at different times during infancy and childhood, nevertheless all the patients showed chronic morbidities since birth and continuous needs to seek medical consultations for various complaints.
Summary, Conclusion and Recommendations
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All patients were thoroughly genetically examined and subjected to karyotyping tests using G-banding Seabright 1971 technique. All patients have normal karyotyping results.
Out of the 25 patients, 14 were considered complex with syndromic and non-syndromic, while 11 were isolated. Six suspected syndromes have been detected named Nicolaides Baraitser syndrome, GATA6 syndrome like phenotype, BWS, Arterial tortuosity syndrome, Aarskog syndrome, and Escobar syndrome. The other eight patients could not be identified solely by clinical manifestations and have no abnormal karyotyping results to define their possible syndromes.
We have detected a de novo pathogenic variant in SMARCA2 gene on chromosome 9, linked to CDH development and causing Nicolaides-Baraitser syndrome using whole exome sequencing in one of these patients, which highlighted the invaluable role of advanced genetic testing in guiding the diagnosis and identifying underlying genetic cause of such a heterogenous birth anomaly.
These reported Nicolaides-Baraitser syndrome and Aarskog-Scott syndrome cases have CDH as one of their anomalies.
Taking in consideration that a) none of the patients have received any genetic counselling before being part of this study, and b) the fact that all patients reported various types of morbidities and disabilities across their life course such as neuro developmental delay in 40% of patients, plus c) the lack of multidisciplinary health services to guide the patients‘ decision and provide adequate care, and d) regarding the success in diagnosing these syndromes with the least available resources; a national programme for surveillance of congenital birth defects and an operationalized action plan to advance genetic services and testing capacities should be the way forward a cost efficient health system supporting a better quality of life for all.