To describe the clinical features and management of ocular choristomas in mosaic RASopathy patients. We performed a retrospective single-center case review of all mosaic RASopathy patients. We evaluated for the presence of corneal and epibulbar choristomas and conducted a comprehensive analysis of the imaging, including operative microscope images, slitlamp images, and optical coherence tomography images. In doing so, we provide a precise description for these types of choristomas. Nine patients with mosaic RASopathies, 7 men and 2 women (3 with clinical diagnoses of Linear Sebaceous Nevus Syndrome, 5 with Oculoectodermal Syndrome, and 1 with Encephalocraniocutaneous Lipomatosis), were evaluated. Fourteen eyes with ocular choristomas were identified among the 9 patients-bilaterally in 5 and unilaterally in 4. Molecular confirmation was available in 6 cases, and pathogenic variants in the KRAS gene were identified in all 6. None of the choristomas presented as discrete raised lesions at the limbus alone; they were all relatively flat, very vascularized, and in 4 of the 14 eyes, there was involvement of the visual axis, with 6 having extension with vascularization onto the cornea. All of them extended into the conjunctiva and into the sclera posteriorly. Ocular choristomas with conjunctival and scleral extension, often with concomitant corneal vessels, should alert the clinician to the possibility of a mosaic RASopathy. Management can be complicated and includes measures such as optical iridectomy, anti-VEGF injections, and refractive correction with occlusion therapy, and corneal transplantation may also be considered.

Cobb Syndrome, or cutaneomeningospinal angiomatosis, is a rare non-hereditary neurocutaneous disorder characterised by spinal arteriovenous malformations (AVMs) and cutaneous vascular lesions within the same metamere. We present a case of Cobb syndrome manifesting as progressive paraparesis due to dorsal compressive myelopathy. Unlike most reported cases, which primarily involve the thoracic spine, this case exhibited extensive vascular malformations affecting all spinal segments, making it a rare presentation. Diagnosis was established through MRI and angiographic studies, revealing vertebral hemangiomas and an epidural AVM causing spinal cord compression. Surgical decompression was performed, leading to partial neurological recovery. This case highlights the importance of early recognition of cutaneous markers in diagnosing neurocutaneous syndromes and underscores the need for prompt neurosurgical intervention to prevent irreversible neurological deficits.

DICER1 tumor predisposition syndrome (DTPS) is a hereditary condition affecting children and young adults. Identification of DICER1 carriers is key for prevention and actionability in families. However, DTPS diagnosis is hindered by its incomplete penetrance and broad phenotypic spectrum. We performed an analysis of DICER1 sequencing data from 92 children and 6108 adults with suspected cancer predisposition syndrome. Clinical and DICER1 somatic data from selected carriers and public data sets were studied. The prevalence of germline DICER1 pathogenic variants was 1:30 in children and 1:3054 in adults. No adult referral phenotype was a known DTPS-associated tumor, although 3 of 5 carriers developed thyroid alterations. We provide functional evidence supporting the pathogenicity of a novel in-frame deletion. A 56-year-old woman with ovarian carcinoma and toxic diffuse thyroid hyperplasia was found to have a postzygotic hotspot missense variant. The prevalence of DICER1 pathogenic variants in cancer predisposition populations was 5 to 6 times that reported in the general population. Pediatric-onset DTPS is well characterized, whereas adult carriers mainly present with thyroid abnormalities in the absence of DICER1-related family history, thus requiring accurate criteria for its identification when in constellation with other tumor types. Postzygotic hotspot missense variants may exist without the expected severe phenotype.

Neurofibromatosis type 1 (NF1; 613113) is a hereditary neurocutaneous disorder that causes tumors in the nervous system, significantly impacting the quality of life (QoL). It is characterized by diverse clinical manifestations, including café-au-lait macules (CALMs), axillary or inguinal freckling, Lisch nodules, skeletal abnormalities, and various types of neurofibromas. Plexiform neurofibromas (PN), a common complication of NF1, are often inoperable and prone to recurrence. The study aimed to describe the clinical characteristics and healthcare burden of NF1, including those with PN and those receiving Selumetinib therapy, in Saudi Arabia. This retrospective observational study was conducted at the National Guard Health Affairs King Abdulaziz Medical City in Saudi Arabia. Patient medical records were retrospectively reviewed from January 2016 to January 2024. We included all patients diagnosed with NF1 who fulfilled the National Institutes of Health (NIH) diagnostic criteria in 2021 or had a confirmed pathogenic NF1 variant on genetic testing. A total of 60 patients with NF1 were included; 55.2% of them were females. CALMs were the most common cardinal criteria, affecting 80% of the patients. Among NF1 patients, 12 had PN (20%). Only four patients received Selumetinib therapy. Genetic testing was performed in 39 patients, revealing pathogenic NF1 variants in 29 (74.4%). Pain medications were used by eight patients (13.3%). NF-1-related pain negatively impacted patients' attention (24%), outdoor activities (24%), and social interactions with friends (20%). Among NF1 patients, 28 (46.7%) required hospitalization, twelve ER visits were conducted by seven (11.7%) NF1 patients, and outpatient services were utilized by nearly all NF1 patients (96.7%), with 1076 outpatient visits. The overall financial burden was high, with NF1 patients incurring $64.5 million, PN patients $13.5 million, and PN patients treated with Selumetinib $3.7 million. This study highlights the clinical and healthcare challenges of NF1 and PN in Saudi Arabia, emphasizing the need for a multidisciplinary approach that combines medical, psychological, and financial support. The limited access to Selumetinib represents a gap. Increasing treatment accessibility and financial support are key to improving the outcomes and QoL.

Wyburn-Mason syndrome is a rare, non-hereditary congenital disease, belonging to the group of neurocutaneous syndromes with fewer than 100 cases reported since its first description in 1937. A young adult man was initially evaluated at the age of 2 years for proptosis and progressive visual impairment of the right eye, followed by impairment in ocular abduction, adduction and elevation as well as amaurosis. MRI revealed an expansive formation centred in the right orbit compromising conal spaces with distortion of eye muscles and optic nerve. The lesion extended through the superior orbital fissure into the right cavernous sinus and to the contralateral orbit. Despite embolisation, proptosis and oedema of the periorbital tissue continued to worsen. The combination of facial, ocular and intracranial vascular malformations and the exclusion of alternative aetiologies led to a diagnosis of cerebrofacial arteriovenous metameric syndrome (CAMS) 1 (Wyburn-Mason syndrome). Important differential diagnoses are other CAMS, such as Sturge-Weber syndrome, as well as other conditions such as retinal cavernous haemangioma and vasoproliferative tumours. The optimal treatment regimen for severe cases of this syndrome is still unclear. Wyburn-Mason syndrome should be considered in patients presenting multiple arteriovenous malformations with orbital apex lesions.