Proteus syndrome caused by novel somatic AKT1 duplication

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Proteus syndrome (PS) is a rare, complex overgrowth disorder characterized by mosaic somatic mutations.
• It leads to asymmetrical bone and fat tissue growth, causing disfigurement and psychological distress.
• The rarity and diverse tissue involvement pose significant challenges for patient care and medical teams.

Observation:

• A Saudi girl presented with a large, antenatally detected cervical mass, identified as a growing cystic hygroma.
• She exhibited features of overgrowth and hemangiomas, consistent with Proteus syndrome.
• Initial whole exome sequencing from blood and affected tissue was inconclusive.

Findings:

• Deletion-duplication analysis of the affected tissue revealed a novel mosaic somatic mutation in the AKT1 gene.
• This finding is crucial for establishing a definitive genetic diagnosis in cases with negative exome sequencing.
• Somatic mutations present diagnostic and therapeutic challenges in rare genetic disorders.

Implications:

• Accurate genetic diagnosis of Proteus syndrome is essential for prognosis and family counseling.
• Geneticists play a vital role in managing patients with mosaic somatic mutations.
• This case underscores the need for advanced genetic testing methods to identify complex mutations in rare diseases.