Differential diagnoses of overgrowth syndromes: the most important clinical and radiological disease manifestations

Abstract

Overgrowth syndromes comprise a heterogeneous group of diseases that are characterized by excessive tissue development. Some of these syndromes may be associated with dysfunction in the receptor tyrosine kinase (RTK)/PI3K/AKT pathway, which results in an increased expression of the insulin receptor. In the current review, four overgrowth syndromes were characterized (Proteus syndrome, Klippel-Trenaunay-Weber syndrome, Madelung's disease, and neurofibromatosis type I) and illustrated using cases from our institution. Because these syndromes have overlapping clinical manifestations and have no established genetic tests for their diagnosis, radiological methods are important contributors to the diagnosis of many of these syndromes. The correlation of genetic discoveries and molecular pathways that may contribute to the phenotypic expression is also of interest, as this may lead to potential therapeutic interventions.

Figure 1

The right costovertebral joint space is fused. The T12 vertebra shows disproportionate asymmetric overgrowth which is characteristic for the Proteus syndrome.

Figure 2

A 21-year-old man with Proteus syndrome presenting asymmetric lower limbs and epidermal nevus. CT of the abdomen showed tissue with a fat density infiltrating the right paraspinal musculature, with increased local volume extending from T7 to L5, in addition to an enlargement of the right kidney (a). The scan also noted fatty replacement in right gluteal muscles (b). Coronal CT showed asymmetry of the kidneys (c).

Figure 3

A 60-year-old man with Klippel-Trenaunay-Weber syndrome presenting asymmetric growth of the lower limbs. CT of the chest showed increased soft tissue as well as extensive vascular malformations in the left hemithorax wall with intermingled phleboliths, causing multiple lytic lesions with enlargement in the ipsilateral ribs (a). CT of the abdomen showed a thick-walled rectum intermingled with phleboliths, denoting varicose veins (b).

Figure 4

A 53-year-old man with Madelung's disease presenting a progressive painless increase of the cervical region. CT of the neck and chest showed fat deposition occurring predominantly in the posterior subcutaneous region of the neck (a) and in the supraclavicular and upper regions of the chest (b).

Figure 5

A 53-year-old man with neurofibromatosis type I. A morphostructural abnormality in the spine is characterized by significant dorsolumbar scoliosis with right convexity, as observed in his CT scan (coronal section).

Figure 6

A 34-year-old woman with neurofibromatosis type I. Axial CT show plexiform neurofibromas of lumbar and sacral nerve roots.