This paper explores a rare congenital condition called encephalocraniocutaneous lipomatosis (ECCL), which affects the eyes, skin and brain. Researchers examined a patient with neurofibromatosis type 1 (NF1), a genetic disorder, who also exhibited the typical features of ECCL. Genetic analysis of brain and other tissues revealed a distinct mosaic pattern of alterations in the NF1 gene, which can explain the ECCL features seen in this patient. These findings suggest that ECCL may be linked to NF1 alterations exhibiting this specific mosaic pattern and originating during early embryonic development. This pattern further mimics the activation of a previously identified biological pathway (RAS-MAPK) in ECCL that is caused by alterations in FGFR1 and KRAS genes. As such, this research highlights how different genetic alterations can lead to a similar congenital condition by affecting the same biological pathway, and further extends the spectrum of congenital conditions seen in NF1 alterations. (By Steven Smeijers, MD, https://jmg.bmj.com/content/early/2024/05/30/jmg-2023-109785 )