isotretinoin and Chromosome-Deletion

Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hypotonia, and congenital malformations. To date, no effective treatment has been found for KdVS, largely due to its unknown pathogenesis. Using siRNA screening, we identified KANSL1 as an essential gene for autophagy. Mechanistic study shows that KANSL1 modulates autophagosome-lysosome fusion for cargo degradation via transcriptional regulation of autophagosomal gene, STX17. Kansl1

Topics: Abnormalities, Multiple; Animals; Autophagosomes; Cerebral Cortex; Chromosome Deletion; Chromosomes, Human, Pair 17; Disease Models, Animal; Female; Haploinsufficiency; HeLa Cells; Humans; Intellectual Disability; Isotretinoin; Lysosomes; Mice; Mice, Transgenic; Mitophagy; Neurons; Nuclear Proteins; Primary Cell Culture

A 15-year-old male individual treated with isotretinoin for acne vulgaris presented with persistent pancytopenia and circulating myeloblasts after discontinuation of the drug. Marrow assessment revealed myelofibrosis (MF) and myeloblasts exhibiting monosomy 7, diagnostic of myelodysplastic syndrome (MDS). Although a popular website seems to associate isotretinoin with MF, no published cases of MF or MDS attributable to this drug were identified. Although we expect that he would eventually have developed MDS and MF, this patient was perhaps identified sooner due to cytopenias accelerated by isotretinoin. This case illustrates that patients exhibiting cytopenias persisting following isotretinoin therapy merit evaluation for underlying hematopoietic disorders.

Topics: Acne Vulgaris; Adolescent; Chromosome Deletion; Chromosomes, Human, Pair 7; Dermatologic Agents; Humans; Isotretinoin; Male; Myelodysplastic Syndromes; Pancytopenia; Primary Myelofibrosis; Prognosis