Pyknodysostosis (Osteopetrosis Acro-Osteolytica)

ABSTRACT Objective To present a case of pyknodysostosis (PKND), a rare genetic cause of skeletal dysplasia that often goes undiagnosed even in patients with classic features. Methods We report a case of PKND that went undiagnosed over many years despite classic features. We performed physical examination, imaging studies, and genetic testing on the patient. Results A 21-year-old female presented to endocrinology to establish care. On evaluation, she was noted to have disproportionate short stature and a past medical history notable for bilateral blindness due to optic atrophy secondary to bone enlargement and thickening of the optic nerve canal before age 7 years. She also had a history of foot fractures occurring with ambulation. Her family history was significant for consanguineous parents and relatives with similar clinical features. Physical examination revealed a short, 128-cm tall female with open anterior and mastoid fontanels, mild frontal bossing and micrognathia, evidence of double rows of teeth, and digits of varied length in both hands and feet. Plain radiographs demonstrated diffuse sclerosis and marked cortical thickening of the pelvis, femurs, metacarpals, proximal phalanges, and metatarsals as well as decreased phalangeal length and acro-osteolysis of the hands and feet. Dual energy X-ray absorptiometry demonstrated increased bone mineral density (z scores +2.5 lumbar spine, +3.7 femoral neck, +4.5 total hip). Genetic testing revealed a exon 5-homozygous mutation in the cathepsin K (CTSK) gene consistent with PKND. Conclusion Patients with PKND come to medical attention for a variety of reasons but often go undiagnosed even when presenting with classic features due to the rarity of the condition and the overlap with other skeletal dysplasias. Abbreviations CTSK cathepsin K PKND pyknodysostosis