Pycnodysostosis (MIM #265800) is a subtype of osteopetrosis and is a rare skeletal dysplasia characterized by generalized progressing osteosclerosis. The prevalence is 1–5/1.000.000. Pycnodysostosis is caused by homozygosity or compound heterozygosity for biallelic pathogenic mutations in the cathepsin K gene (CTSK). Insufficient activity of cathepsin K within osteoclasts leads to incomplete bone resorption. Heterozygotic carriers of the mutations have reduced levels of cathepsin K but a normal phenotype.

Pycnodysostosis is a systemic skeletal disorder presenting with short stature, facial dysmorphology, maxillary and mandibular hypoplasia, stridor, laryngomalacia and sleep apnea. In addition, osteolysis of the acromial end of the clavicles and brachydactyly are common. There is a generalized, progressive osteosclerosis of the skeleton associated with bone fragility, most frequently affecting the lower extremities. Intraorally, the patients often have a grooved and narrow palate nearly always crowded and misaligned teeth.

Isolated growth hormone deficiency or pituitary hypoplasia is found in some patients, but the outcome of growth hormone therapy is variable.

Patients with pycnodysostosis have a normal life expectancy. However, craniosynostosis, low energy fractures, chronic pain, respiratory problems and sleep apnea, and dental complications may cause significant morbidity and reduce quality of life.

We recommend that patients with pycnodysostosis receive care in a multidisciplinary setting providing access to experienced pediatric or adult endocrinologists, orthopedic surgeons, dentists, craniofacial surgeons, specialists in respiratory medicine, neurology, ophthalmology, and audiology, and physio- and occupational therapists familiar with skeletal dysplasias including osteopetroses.