Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Abramson Research Center, Room 716D, 3615 Civic Center Blvd., Philadelphia, PA 19104, United States; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address:
Published: July 2020
AI Article Synopsis
Article Abstract
Gain of function variants in SAMD9 cause MIRAGE syndrome, a rare Mendelian disorder that results in myeloid dysplastic syndrome (MDS), poor immune response, restricted growth, adrenal insufficiency, ambiguous genitalia, feeding difficulties and most often significantly reduced lifespan. In this study, we describe histomorphologic and genetic changes occurring in serial bone marrow measurements in a patient with MIRAGE syndrome and untreated MDS of 9 years. Histomorphological analysis during childhood showed progressive hypocellularity with erythroid and megakaryocytic dysplasia and cytogenetic testing demonstrated monosomy 7. Serial leukemia gene panel testing performed over a seven year period revealed multiple pre-leukemic clones arising at age 7 years followed by sequential mutational events in ETV6 and RUNX1 driving acute myeloid leukemia (AML) at age 9. Comprehensive genotype-phenotype analysis with 28 previously reported patients found the presence of MDS did not impact overall survival, but in silico variant pathogenicity prediction scores for SAMD9 distinguished patients with poor prognosis. Overall, our analysis shows progression of MDS to AML can be monitored by following mutation evolution in leukemia related genes in patients with MIRAGE syndrome, and specific SAMD9 mutations likely influence disease severity and overall survival.
An infant with intrauterine growth restriction, suspected of having MIRAGE syndrome based on prenatal ultrasound, presented with genital ambiguity, adrenal insufficiency, intractable diarrhea from birth, and a pathogenic mutation (). Endoscopic biopsies of the duodenum revealed complex light and electron microscopic abnormalities. Hypoplastic villi without signs of enteritis suggests a disorder of mucosal growth with reduced absorptive surface area contributes to intractable diarrhea.
We present a case of a thumb metacarpophalangeal (MCP) joint dislocation complicated by the interposition of the sesamoid bones. This case highlights a clinical scenario referred to as the "locked thumb" syndrome, in which a first-digit MCP dislocation is complicated by an entrapped anatomical structure that hinders closed reduction. In this case, the thumb sesamoid bones became lodged at the base of the dislocated proximal phalanx.
- Aromatase inhibitors, especially letrozole (LZ), are now recognized as effective first-line treatments for inducing ovulation and enhancing intrauterine insemination outcomes.
- LZ is gaining traction as an adjunct to gonadotropin therapy in IVF, particularly beneficial for women with estrogen-sensitive cancers, by lowering estrogen levels.
- Recent studies suggest that LZ can aid poor responders in IVF, mitigate ovarian hyperstimulation syndrome, and improve the luteal phase, while also being useful for preparing the endometrium in frozen-thawed embryo transfers.
5-azacitidine is a treatment for myelodysplastic syndrome (MDS) and certain myeloproliferative neoplasms (MPNs), but it can cause side effects like myelosuppression and nausea, with rare, serious allergic reactions.
A case study describes a 71-year-old man with MDS/MPN who experienced repeated episodes of angioedema after starting 5-azacitidine, affecting various body areas and deemed causally linked to the medication.
After discontinuing 5-azacitidine due to ongoing angioedema, the patient responded well to steroids and is now managing his blood condition with low-dose hydroxyurea, while the exact cause
