This is a rare case of primary pachydermoperiostosis (PDP). A 28-year-old Filipino male presented with a lifelong history of enlarged hands and feet. He eventually developed symmetrical swelling of the ankles and knees associated with leg heaviness and knee pain with difficulty with ambulation, hence consult. His eldest brother also had the same “elephant-like” extremities. He had cutis vertices gyrata with a thickened corrugated hair pattern, deep lines on the forehead, deepened nasolabial folds, enlarged extremities especially distally, with coarse, thick skin, and prominent clubbing. The nails were convex “watch crystal-like.” The wrists, knees, and ankles were tender and enlarged, with massive effusion of the knees. All joints were devoid of warmth and erythema. Skeletal survey favored hypertrophic osteoarthropathy over acromegaly, with periosteal thickening of the metaphysis and digital clubbing. The filarial smear was negative for blood parasites. Skin biopsy showed keratoderma. Synovial fluid was non-inflammatory while arthroscopic synovial biopsy showed chronic inflammation eosinophilic amorphous tissue. Electrocardiogram, echocardiogram, thyroid function tests, complete blood count, peripheral blood smear, serum chemistries, coagulation tests, urinalysis, urine electrolytes, fecalysis, and chest CT scan were unremarkable. Whole abdomen ultrasound revealed the liver parenchymal disease. Hepatitis profile revealed chronic infection with hepatitis B, with low infectivity. The three major criteria for PDP (pachydermia, periostitis, and digital clubbing) were fulfilled. Possible secondary causes were either excluded or were non-contributory. He was started on analgesics and anti-inflammatory medicines. Repeated arthrocenteses drained liters of synovial fluid per knee, and along with intra-articular steroid injections and compressive bandages, temporarily relieved his bilateral knee pain. He was referred to rehabilitation to maximize his range of motion and to address body image issues. The patient remains on regular follow-up for periodic arthrocentesis. The option of anti-VEGF treatment and arthrotomy was explored as possibilities but were not deemed practical. PDP is a rare genodermatosis. Life span is not affected but the quality of life is dismal without supportive management, as there is no known cure. A multidisciplinary team composed of a rheumatologist, dermatologist, orthopedic surgeon, plastic surgeon, rehabilitation physician, and a psychiatrist should be available to assist in the needs of these patients.
Osteoarthropathy, Primary Hypertrophic

OBJECTIVETo detect mutation of HPGD gene among three pedigrees affected with primary hypertrophic osteoarthropathy (PHO) by DNA sequencing and high-resolution melting (HRM) analysis.

METHODSGenomic DNA was extracted from peripheral blood samples collected from the pedigrees. PCR and direct sequencing were carried out to identify potential mutations of the HPGD gene. Amplicons containing the mutation spot were generated by nested PCR. The products were then subjected to HRM analysis using the HR-1 instrument. Direct sequencing was carried out in family members and healthy individuals to confirm the result of HRM analysis.

RESULTSA homozygous mutation c.310_311delCT was detected in 2 affected probands, while a heterozygous mutation c.310_311delCT was detected in the third proband. HRM analysis of the fragments encompassing HPGD exon 3 showed 3 curve patterns representing three different genotypes, i.e., the wild type, the c.310_311delCT homozygote, and the c.310_311delCT heterozygote. Result of DNA sequencing was consistent with that of the HRM analysis and phenotype of the subjects.

CONCLUSIONThe c.310_311delCT mutation may be the most prevalent mutation among Chinese population. HRM analysis has provided an optimized method for genetic testing of HPGD mutation for its simplicity, rapid turnover and high sensitivity.

Adult ; Child ; Female ; Humans ; Hydroxyprostaglandin Dehydrogenases ; genetics ; Male ; Mutation ; Osteoarthropathy, Primary Hypertrophic ; genetics ; Pedigree

Pachydermoperiostosis (PDP) is a male predominant rare genodermatosis. Various clinical presentations includes pachydermia (thickened and folded skin), periostosis and digital clubbing. Both the skin and the extremity findings are seen in the complete form, whereas the incomplete form lacks the skin findings. We report a case of primary form of pachydermoperiostosis together with literature review.
Extremities ; Humans ; Male ; Osteoarthropathy, Primary Hypertrophic* ; Rhytidoplasty ; Skin

Pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, is a rare genetic disease affecting both skin and bones. Both autosomal dominant with incomplete penetrance and recessive inheritance of PDP have been previously confirmed. Recently, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1) were reported as pathogenic genes responsible for PDP. Both genes are involved in prostaglandin E2 (PGE2) degradation. We aimed to identify responsible genes for PDP and the clinical features in Korean patients with PDP. Six affected individuals and their available healthy family members from three unrelated Korean families with PDP were studied. All of the patients displayed complete phenotypes of PDP with finger clubbing, pachydermia, and periostosis. Mutation analysis revealed a novel heterozygous mutation in the SLCO2A1 gene at nucleotide 302 causing a substitution of the amino acid isoleucine to serine at codon 101 (p.IIe101Ser) in affected individuals. We also identified known SLCO2A1 mutations, one homozygous for c.940+1G>A, and another compound heterozygous for c.940+1G>A and c.1807C>T (p.Arg603*) from two PDP families. Genetic analyses of the PDP patients showed no abnormality in the HPGD gene. Our study further supports the role of mutations in the SLCO2A1 gene in the pathogenesis of PDP and could provide additional clues to the genotype-phenotype relations of PDP.
Bone and Bones/diagnostic imaging ; Child, Preschool ; DNA Mutational Analysis ; Exons ; Heterozygote ; Humans ; Male ; Middle Aged ; Organic Anion Transporters/*genetics ; Osteoarthropathy, Primary Hypertrophic/diagnostic imaging/*genetics/pathology ; Pedigree ; Phenotype ; Polymorphism, Genetic ; Positron-Emission Tomography ; Young Adult

Pachydermoperiostosis is a rare genetic disease characterized by finger clubbing, periostosis, cutis verticis gyrata and pachydermia accompanied by acroosteolysis and hyperhidrosis. Recently, two susceptibility genes, HPGD and SLCO2A1, have been identified, whose protein products are involved in the transportation of prostaglandin and metabolism underlying pachydermoperiostosis. Here the genetic basis of pachydermoperiostosis and its correlation with its clinical phenotype are reviewed, which may provide a reference for basic research and clinic diagnosis for the disease.
Animals ; Humans ; Hydroxyprostaglandin Dehydrogenases ; genetics ; Organic Anion Transporters ; genetics ; Osteoarthropathy, Primary Hypertrophic ; diagnosis ; genetics ; therapy ; Phenotype

Pachydermoperiostosis (PDP) is a primary hypertrophic osteoarthropathy characterized by digital clubbing, pachydermia, and periostosis, which is inherited as an autosomal dominant or recessive trait. We report on a patient suffering from bilateral knee arthritis for 6 years who was newly diagnosed as PDP. PDP was confirmed by bilateral digital clubbing, hyperhidrosis, and cutis verticis gyrata, findings of pachydermatosis on the forehead and scalp, X-ray findings of proliferative periostitis. This case indicates that PDP is one of several possible rare diseases that should be considered in patients with undifferentiated arthritis.
Arthritis* ; Forehead ; Humans ; Hyperhidrosis ; Knee ; Osteoarthropathy, Primary Hypertrophic* ; Periostitis ; Rare Diseases ; Scalp

OBJECTIVETo identify the genetic cause for a Chinese Han family affected with primary hypertrophic osteoarthropathy.

METHODSWhole blood and urine samples were collected from a patient and 7 unaffected relatives of the family. The coding sequences and intron/exon boundaries of HPGD and SLCO2A1 genes of the patient were amplified with polymerase chain reaction and sequenced. The genotypes of relatives were subsequently verified. Urinary prostaglandin level was measured with enzyme-linked immunosorbent assay (ELISA).

RESULTSA homozygous 2-bp deletion in HPGD gene (c.310_311delCT, or p.L104AfsX3) was detected in the patient, and 5 heterozygous carriers were identified in the relatives. The urinary prostaglandin E2 (PGE2) level was significantly elevated (P<0.01), while PGE-M was significantly reduced (P<0.01) in the patient.

CONCLUSIONPrimary hypertrophic osteoarthropathy in this family is caused by a homozygous mutation (c.310_311delCT) in the HPGD gene.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Dinoprostone ; urine ; Female ; Humans ; Hydroxyprostaglandin Dehydrogenases ; genetics ; Male ; Molecular Sequence Data ; Mutation ; Organic Anion Transporters ; genetics ; Osteoarthropathy, Primary Hypertrophic ; diagnosis ; enzymology ; ethnology ; genetics ; Pedigree

No abstract available.
Osteoarthropathy, Primary Hypertrophic* ; Peptic Ulcer* ; Polyps* ; Stomach*

Touraine-Soulente-Gole Syndrome (TSG) or pachydermoperiostosis is a rare disorder characterized by pachydermia, periostosis & digital clubbing. Herein, we report a case of a 27 year old male, with the looks of a 47 year old. He presented with excessive wrinkling on his face since past 8 years. TSG syndrome was suspected and examined by histopathological, endocrinological and radiological studies for the confirmation of clinical diagnosis.
Humans ; Male ; Osteoarthropathy, Primary Hypertrophic

Touraine-Soulente-Gole Syndrome (TSG) or pachydermoperiostosis is a rare disorder characterized by pachydermia, periostosis & digital clubbing. Herein, we report a case of a 27 year old male, with the looks of a 47 year old. He presented with excessive wrinkling on his face since past 8 years. TSG syndrome was suspected and examined by histopathological, endocrinological and radiological studies for the confirmation of clinical diagnosis.
Humans ; Male ; Osteoarthropathy, Primary Hypertrophic