Presentation of clinical features of microcephalic primordial dwarfism associated with a rare variant in the DNMT3A gene and synchronous epiglottic and esophageal cancers
Year: 2025
Type: article
Study design: Case Report
Abstract: Microcephalic primordial dwarfism (MPD) has been associated with germline gain-of-function of DNMT3A which is a gene encoding for a DNA methyltransferase 3 alpha, involved in epigenetic regulation, especially during embryonic development [1]. Somatic variants in DNMT3A have been widely studied in different types of tumors, including acute myeloid leukemia, hematopoietic and lymphoid cancers. This report describes the case of a 37-year-old male with clinical features of MPD and heterozygous for a variant in the DNMT3A gene, c.911_913del:p.(Ser304del) in exon 8, who presented with severe weight loss and dysphagia and found with two synchronous distinct masses in the epiglottis and upper esophagus. Endoscopy guided biopsies of the epiglottic mass showed a poorly differentiated squamous cell carcinoma (SCC), and esophageal biopsy was consistent with a well to moderately differentiated SCC with keratinization. Next Generation sequence analysis (NGS) of both cancers showed overlapping pathways involving TP53 and MUTYH and similar PD-L1 combined positive score (CPS). The patient was treated with palliative radiation according to the Quad Shot regimen on the epiglottic and esophageal masses. Unfortunately, he deteriorated rapidly, and the family decided to transition to hospice care. This is the first case of a patient with clinical features of MPD and heterozygous for an in-frame deletion of DNMT3A, developing two synchronous cancers.
Source: Medical Reports
Authors: Iole Ribizzi-Akhtar, Shaolei Lu, Maania Naseem
Institutions: Brown University, Rhode Island Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $1,900
OpenAlex ID: W4410618707