Pachydermoperiostosis: The value of molecular diagnosis

Summary Background Pachydermoperiostosis is a rare autosomal recessive genetic disorder characterized by the association of periostosis and pachydermia. To date, two genes involved in prostaglandin metabolism, HPGD and SLCO2A1, have been identified. Patients and methods A 7-year-old girl presented digital clubbing of the hands and feet, curved nails, hyperhidrosis, and pachydermia, as well as eczema of the trunk and limbs. The diagnosis of pachydermoperiostosis was confirmed by the detection of a homozygous mutation in the HPGD gene. The second case concerned a 41-year-old male with acral and cephalic pachydermia (cutis verticis gyrata), and palmoplantar keratoderma. Bone X-rays showed changes in the distal ends of several bones. The diagnosis of pachydermoperiostosis was confirmed by the detection of a homozygous mutation in the SLCO2A1 gene. Discussion The genotype/phenotype correlation suggests that patients with SLCO2A1 mutations will develop the symptoms later in life, but that these will be more severe, with a greater likelihood of cutis verticis gyrata and joint involvement compared with patients presenting HPGD mutations. In addition, hereditary enteropathy has recently been described in patients with SLCO2A1 mutations, which could account for the gastrointestinal picture seen in the second patient. Finally, on account of cases involving myelofibrosis associated with mutations in the SLCO2A gene, these patients should have a hematologic follow-up. Conclusion Given the genotype/phenotype correlations illustrated by these cases, it would appear useful to propose molecular diagnosis for patients presenting pachydermoperiostosis.