In a young patient referred to the Institute of Human Genetics at the University Medical Center Göttingen, the clinical suspicion of Proteus syndrome was made and confirmed by molecular genetic diagnostics. The patient presented with a progressively protruding frontal bone due to an intraosseus lipoma (a benign tumor of fat tissue) and, additionally, mild developmental delay, unilateral hearing impairment, strabism and a dermoid of the eye. DNA analysis performed on a tissue sample yielded from the lipoma showed that the patient carries a specific heterozygous variant of the AKT1 gene that is known to cause Proteus syndrome. This variant is present in a mosaic state, i.e. it occurred spontaneously as a de novo mutation after fertilization at some point in embryonic development. Therefore, it is not present in every cell of the body. Mosaic genetic variants are more difficult to detect in molecular diagnostics. In such cases, a clinical suspicion of an underlying mosaic disorder and selection of an appropriate sample for genetic testing are crucially important, because analysis of standard blood samples will usually not reveal the causative variant.

Proteus syndrome is a very rare disorder and only occurs in a mosaic form. Its clinical manifestations vary considerably, depending on which cells and tissues are affected by the genetic defect. The syndrome is characterized by disproportionate and asymmetric overgrowth affecting some parts of the patient’s body and by specific skin anomalies. As the researchers report in Clinical Genetics, their patient is the first case of a molecularly confirmed Proteus syndrome with a progressive intraosseous lipoma of the frontal bone but without other, characteristic features – in particular without any suggestive skin anomalies. For the patient, the correct molecular diagnosis may also have implications for novel treatment options, because AKT1-inhibiting substances are available and are already applied in clinical studies.