To make a diagnosis of PS, one must have all the general criteria and various specific criteria. The revised diagnostic criteria for PS are given in the Table.3 According to the diagnostic criteria, our patient fulfilled the mandatory general criteria and had plantar CCTN, epidermal nevus, and dysregulated adipose tissue. The CCTN has notable diagnostic value in mildly affected patients, as it is absent in diseases included in the differential diagnosis such as neurofibromatosis, Klippel-Trenaunay-Weber syndrome, Maffucci syndrome, and Bannayan-Riley-Ruvalcaba syndrome. Hemihyperplasia-multiple lipomatosis syndrome and CLOVES (congenital, lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/spinal/skeletal anomalies) syndrome also can present on the plantar surfaces, and lesions may be overgrown at birth but are softer and compressible, have wrinkles instead of deep folds, and tend to grow with the child rather than disproportionately as in PS.4
The epidermal nevi and vascular malformations generally do not spread or increase in number. In contrast, CCTN in PS grows throughout childhood but tends to remain stable in adulthood.4 Postponing surgical treatment until skin lesions stabilize appears to be the best option. However, for practical purposes, surgical intervention may be required at an earlier phase to address the severe functional and cosmetic consequences. Some patients require multiple orthopedic procedures over the ensuing years or decades to control the hyperplasia.3 New CCTN that developed from the prior surgical incision, macrodactyly of the fourth and fifth right toes, and scoliosis appeared when the patient came to our clinic for retreatment 1 year after the initial presentation. The asymmetrical and disproportionate overgrowth of tissues had moderately accelerated in that period. Considering the increasingly impaired walking, we performed a second surgery. On follow-up visits, the patient expressed improvement in daily life.
Studies had been performed to clarify the genetic bases of PS, and the somatic activating mutation in AKT1 (AKT serine/threonine kinase 1) was reported to be the cause of the disease.5,6 Germline PTEN (phosphatase and tensin homolog) mutations have been identified in some patients with overgrowth abnormalities of PS. However, given the misdiagnosis of PS with PTEN mutations and the notion that a gene alone cannot result in PS, the loss-of-function mutations of LEMD3 that have been reported in familial cutaneous collagenomas also may be related to the abnormal growth of connective and bone tissues that are typical of PS.7,8 Lindhurst et al5 concluded that PS is caused by a somatic activating mutation in AKT1, which proved the hypothesis of somatic mosaicism and implicated activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. AKT1 is activated by loss-of-function mutations in PTEN, which explains why patients with these mutations (eg, those with the segmental overgrowth, lipomatosis, arteriovenous malformation, epidermal nevus, SOLAMEN [segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus] syndrome) and patients with activating mutations in AKT1 (eg, those with PS) have overlapping but distinct clinical manifestations. Molecular genetic testing may be useful to confirm the diagnosis in individuals who meet clinical criteria and to establish the diagnosis in individuals with clinical findings that are ambiguous or mild. Further studies are necessary to progress the understanding and management of PS, which will require cooperation of geneticists, surgeons, and other specialists.