Proteus syndrome with syringohydromyelia and arachnoid cyst

Abstract

The authors make a good review of the main clinical and genetic aspects of Proteus syndrome. They also describe new neuroimaging findings with clinical significance that must be added to the variety of abnormalities in these rare multi-organic neurocutaneous syndrome. With regard to molecular genetics, Zhou et al. [3] reported a boy with congenital hemihypertrophy, epidermoid nevi, macrocephaly, lipomas, arteriovenous malformations, and normal intellect. The patient had the clinical diagnosis of Proteuslike syndrome. Sequence analysis of DNA from peripheral blood revealed heterozygosity for a single base transversion resulting in an Arg 335 to Ter substitution of the phosphatase and tensin homolog (PTEN) gene product, whereas analysis of the DNA from nevus, lipoma, and arteriovenous mass also revealed heterozygosity for Arg 130 to Ter. The former mutation had been reported in patients with Cowden syndrome, whereas the latter mutation had been reported in individuals with Bannayan– Zonana syndrome. The authors postulated that the second hit, Arg 130 to Ter, occurred early in embryonic development and may even represent germline mosaicism. Thus, PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future. Five unrelated patients with Proteus syndrome had no demonstrable mutations in PTEN. Smith et al. [2] described a 16-month-old male with a de novo 1-bp deletion in the cDNA of the PTEN gene, 507 delC, and classic features of Proteus syndrome, including a left-sided epidermal nevus following the lines of Blaschko, widespread capillary venous malformation on his chest and abdomen, multiple lipoblastomata, disproportionate overgrowth of the right leg with progressive course. They concludedthatthe demonstration ofagermlinePTEN mutationin Proteus syndrome permitted its classification, along with Cowden and Bannayan–Zonana syndromes, as part of the spectrum of PTEN hamartoma–tumor syndromes (PHTS). Thiffault et al. [1] stated that the most plausible suggestion for the genetic basis of Proteus syndrome is the somatic mosaic hypothesis postulated by Happle in 1999, although no somatic mutations in candidate genes had been reported. Because germline mutations in the PTEN gene had been identified in patients with Proteus syndrome, screened affected and unaffected tissue from six patients with Proteus syndrome were done by direct sequencing of genomic DNA for germline or somatic mutations in PTEN or GPC3. No intra-axonic mutations were identified, indicating that neither PTEN nor GPC3 was likely to have a major role in the etiology of Proteus syndrome in this series of cases.