The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.

OBJECTIVES: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification. METHODS: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747. RESULTS: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%). CONCLUSION: The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.

Ameloblastoma: biological profile of 3677 cases.

Available literature on ameloblastoma of the jaw was reviewed, including publications from 1960 to 1993, and compared to the latest larger review, published by Small and Waldron in 1955. The average age of patients with ameloblastoma is 36 years. In developing countries ameloblastomas occur in younger patients. Men and women are equally affected. Women are 4 years younger than men when ameloblastomas first occur, and the tumours appear to be larger in females. Dominant clinical symptoms such as painless swelling and slow growth are non-characteristic. The ratio of ameloblastoma of the mandible to maxilla is 5 to 1. Ameloblastomas of the mandible occur 12 years earlier than those of the maxilla. Ameloblastomas occur most frequently in the molar region of the mandible. In Blacks, ameloblastomas occur more frequently in the anterior region of the jaws. Radiologically, 50% of ameloblastomas appear as multilocular radiolucent lesions with sharp delineation. Histologically, one-third are plexiform, one-third follicular; other variants such as acanthomatous ameloblastoma occur in older patients. Two percent of ameloblastomas are peripheral tumours. Unicystic ameloblastomas occurring in younger patients have been found in 6%. Detailed data on 345 patients with ameloblastoma were evaluated for clarification of therapeutic approaches. Chemotherapy and radiation seem to be contraindicated. Ameloblastomas of the maxilla should be treated as radically as possible, ameloblastomas of the mandible should also be treated radically. However, ameloblastomas which radiologically appear as unilocular lesions may be treated conservatively (enucleation, curettage), whenever all areas of the cystic lumen are controllable intraoperatively. Unicystic ameloblastomas occurring in patients 15 years younger than those with multisystic ameloblastoma may be treated conservatively except in cases with invasion of epithelium into the cyst wall. Different recurrence rates have been found for histological variants of the ameloblastoma. Follicular ameloblastomas appear to recur more often than the plexiform type. Unicystic ameloblastomas reveal lower recurrence rates than "non-unicystic" ameloblastomas. The peripheral type of ameloblastoma may be excised, since conservative therapy results in low recurrence rates. Postoperative follow-up is most important in the therapy of ameloblastoma, because more than 50% of all recurrences occur within 5 years postoperatively.