RESUMEN
Mesenteric plexiform neurofibroma is a subtype of plexiform neurofibroma that involves the mesentery and causes a variety of gastrointestinal complaints. Plexiform neurofibroma is classically found in patients with neurofibromatosis type 1, although genetic contributions to plexiform neurofibroma pathogenesis are heterogeneous. We report the first case of mesenteric plexiform neurofibroma in a patient with a YPEL3 pathogenic variant. This patient presented with growth failure, generalized abdominal pain and chronic diarrhea. She was confirmed to have mesenteric plexiform neurofibroma on histopathology and targeted sequencing on affected tissue confirmed that there were no neurofibromatosis type 1 variants present. Given that this patient's mesenteric plexiform neurofibroma is associated with YPEL3 dysfunction, she is unlikely to benefit from MEK inhibitors, which are the newly approved treatment for inoperable plexiform neurofibroma in patients with neurofibromatosis type 1.
RESUMEN
Muenke syndrome (MIM #602849), the most common syndromic craniosynostosis, results from the recurrent pathogenic p.P250R variant in FGFR3. Affected patients exhibit wide phenotypic variability. Common features include coronal craniosynostosis, hearing loss, carpal and tarsal anomalies, and developmental/behavioral issues. Our study examined the phenotypic findings, medical management, and surgical outcomes in a cohort of 26 probands with Muenke syndrome identified at the Children's Hospital of Philadelphia. All probands had craniosynostosis; 69.7% had bicoronal synostosis only, or bicoronal and additional suture synostosis. Three male patients had autism spectrum disorder. Recurrent ear infections were the most common comorbidity, and myringotomy tube placement the most common extracranial surgical procedure. Most patients (76%) required only one fronto-orbital advancement. de novo mutations were confirmed in 33% of the families in which proband and both parents were genetically tested, while in the remaining 66% one of the parents was a mutation carrier. In affected parents, 40% had craniosynostosis, including 71% of mothers and 13% of fathers. We additionally analyzed the medical resource utilization of probands with Muenke syndrome. To our knowledge, these data represent the first comprehensive examination of long-term management in a large cohort of patients with Muenke syndrome. Our study adds valuable information regarding neuropsychiatric and medical comorbidities, and highlights findings in affected relatives.
