Who it affects: YRTS follows an autosomal‑dominant inheritance pattern, meaning a single altered copy of the gene can cause disease. Both males and females are equally affected, and symptoms often begin in childhood or early adulthood, though some cases are identified later in life.

Prevalence: Because the condition was only formally described in 2020, exact prevalence is uncertain. Current estimates suggest it accounts for < 1 % of all hereditary tumor‑predisposition syndromes, with fewer than 200 molecularly confirmed families reported worldwide (NIH, 2022).

Symptoms

YRTS is a multisystem disorder. Not every individual will experience all manifestations, but the most commonly reported features include:

Central nervous system

• Low‑grade gliomas – especially pilocytic astrocytoma in the cerebellum or optic pathway.
• Choroidal hemangiomas – vascular lesions of the eye that can cause visual disturbances.
• Meningiomas – usually benign but may require surgical removal.

Head and neck

• Parotid gland adenomas – painless swellings that may become malignant in rare cases.
• Branchial cleft cysts – congenital neck cysts that can become infected.

Skin and soft tissue

• Cutaneous hemangiomas – reddish birthmarks that may thicken over time.
• Fibro‑fatty “hamartomas” – benign masses found in the trunk or extremities.

Gastrointestinal & thoracic

• Bronchial carcinoids – low‑grade neuroendocrine tumors of the lungs.
• Gastrointestinal polyps – chiefly hyperplastic or hamartomatous, occasionally progressing to adenocarcinoma.

Endocrine & metabolic

• Dysfunctional thyroid nodules – may present as a goiter or hyperthyroidism.
• Growth hormone excess (rare) – leading to tall stature or acromegaloid changes.

Other systemic features

• Hearing loss due to inner‑ear vascular malformations.
• Developmental delays in a minority of children, often linked to large brain lesions.

Because the phenotype is highly variable, a detailed family history and genetic testing are essential for accurate diagnosis.

Causes and Risk Factors

The root cause is a germline (inherited) pathogenic variant in the YAP1 gene located on chromosome 11q22.1. Most mutations are loss‑of‑function or missense variants that hyperactivate YAP1’s transcription‑co‑activator function.

Genetic mechanism

• Autosomal‑dominant inheritance: each child of an affected parent has a 50 % chance of inheriting the variant.
• De novo mutations: up to 15 % of cases arise spontaneously, without a family history (CDC Genomics).

Who is at higher risk?

• First‑degree relatives of a confirmed case.
• Individuals with early‑onset (< 30 years) low‑grade gliomas or unexplained hemangiomas.
• People who have multiple, histologically distinct tumors across different organs.

Environmental exposures (e.g., radiation) do not appear to trigger YRTS, but they can exacerbate tumor growth in already predisposed individuals, underscoring the importance of routine surveillance.

Diagnosis

Diagnosing YRTS requires a combination of clinical evaluation, imaging, pathology, and molecular genetics.

Clinical assessment

• Comprehensive personal and family cancer history.
• Physical examination focusing on skin lesions, head/neck masses, and visual/auditory function.

Imaging studies

• MRI of the brain and spine – Gold standard for detecting low‑grade gliomas or meningiomas.
• CT or MRI of the chest/abdomen – Evaluates bronchial carcinoids, parotid lesions, and gastrointestinal polyps.
• Ultrasound of neck – Useful for branchial cleft cysts and thyroid nodules.

Pathology

Biopsy of any suspicious mass is performed. Histology frequently shows:

• Low‑mitotic index, GFAP‑positive astrocytomas.
• Positive immunostaining for YAP1 nuclear localization in tumor cells—an emerging diagnostic marker (Cancer Letters, 2021).

Molecular testing

The definitive test is a germline DNA sequencing panel that includes YAP1. Techniques used:

• Next‑generation sequencing (NGS) of a hereditary cancer gene panel.
• Sanger confirmation of identified variants.
• Multiplex ligation‑dependent probe amplification (MLPA) for copy‑number changes.

Guidelines from the American College of Medical Genetics (ACMG) recommend reporting any pathogenic or likely‑pathogenic YAP1 variant as clinically significant (ACMG, 2023).

Treatment Options

Treatment is individualized, focusing on tumor control, symptom relief, and long‑term surveillance.

Surgical management

• **Resection** of accessible tumors (e.g., parotid adenomas, cerebral low‑grade gliomas) is first‑line.
• Microsurgical techniques aim to preserve function, especially in eloquent brain regions.

Medical therapies

• Targeted therapy: Early‑phase trials of TEAD inhibitors (downstream of YAP1) have shown tumor‑size reduction in refractory cases (NIH, 2023).
• Somatostatin analogs (e.g., octreotide) for bronchial carcinoids.
• Corticosteroids** for symptomatic edema surrounding CNS tumors.