Pachydermoperiostosis in an African patient caused by a Chinese/Japanese SLCO2A1 mutation—Case report and review of literature

Abstract

Objectives

Pachydermoperiostosis is a rare clinical entity characterized by skin thickening of the forehead, eyelids, and hands, digital clubbing, and periostosis. Two genes have been associated, HPGD and recently SLCO2A1. We present a detailed clinical and genetic description of an African pachydermoperiostosis patient with a SLCO2A1 mutation.

Methods

Standard clinical and laboratory evaluation was carried out. Genetic screening was done with PCR followed by direct sequencing. We discuss the clinical features and known mutations of previously reported cases identified through a PubMed literature review.

Results

The clinical findings showed special features, including exuberant knee effusions and an extraordinary good response on surgery of the blepharoptosis. We found a splice site mutation in the SLCO2A1 gene in homozygous form: c.940+1G>A. This mutation was previously reported only in 1 Chinese and 3 Japanese cases and was considered as a founder mutation in Japan. Beside our case, only one other patient in the literature carried this mutation in homozygous condition, but with different main clinical symptoms.

Conclusions

Our case demonstrates phenotypic heterogeneity of PDP even between homozygous carriers of the same mutation, suggesting further modifiers. Besides, it shows that this rare SLCO2A1 mutation is not exclusively present in East-Asia, but can occur in various ethnicities, with different origin, thus the incidence is probably underestimated.

Introduction

Pachydermoperiostosis is a rare multi-organic disease characterized by periostosis and hypertrophy of the bones and surrounding soft tissues, accompanied by cutaneous manifestations, including pachydermia, coarsening of facial features, cutis verticis gyrata, marked digital clubbing, hyperhidrosis, seborrhea, acne lesions, and folliculitis [1]. Blepharoptosis is also a manifestation of this clinical entity, which can lead to the need for ophthalmological surgery [2], [3]. Other reported ocular manifestations include corneal leukoma, cataract formation, presenile macular dystrophy, and Bowman layer dystrophy [4]. Severe arthritis of the knees and ankles can also occur, with disabling pain and loss of function [5], [6]. However, synovial fluid does not show inflammatory findings [6]. The manifestations usually start at puberty, evolving slowly over 5–20 years, and then tend to stabilize. Men are more frequently affected than women (9:1) [7].

In recent years, association with 2 genes has been described: HPGD (Chr 4q34.1, MIM 601688), which codes for 15-hydroxyprostaglandin dehydrogenase, and recently SLCO2A1 (Chr 3q22.1-q22.2, MIM 601460), which codes for a prostaglandin transporter protein. Until now, only few cases with mutations in these genes have been reported. Patients of various ethnicities are found; however, some ethnicity-typical mutations and a Japanese founder mutation were already described. Clear genotype/phenotype associations have not been observed.