Clinical Guidance

Pycnodysostosis is characterized by short stature, typical facial appearance (small jaw with obtuse mandibular angle and convex nasal ridge), osteosclerosis with increased bone fragility, acroosteolysis of the distal phalanges, delayed closure of the cranial sutures, and dysplasia of the clavicle. In affected individuals, the facial features become more prominent with age, likely due to progressive acroosteolysis of the facial bones, but can usually be appreciated from early childhood, particularly the small jaw and convex nasal ridge . A comprehensive review of previously published reports identified 159 individuals including 59 unrelated families with confirmed homozygous or compound heterozygous pathogenic variants in CTSK.

Source: GeneReviews — "Pycnodysostosis"

Differential Diagnosis

It is critical to distinguish pycnodysostosis from other primary sclerosing conditions of bone characterized by osteopetrosis, since early hematopoietic stem cell transplantation may be a therapeutic option in some forms of osteopetrosis, whereas it would be of no benefit in individuals with pycnodysostosis, which rarely presents with bone marrow insufficiency .

Table 3.

Disorders Characterized by Osteopetrosis in the Differential Diagnosis of Pycnodysostosis

Features of DifferentialDisorder Overlappingw/Pycnodysostosis | Gene(s) | Differential Disorder | MOI | Features of DIfferential Disorder Not Observed in Pycnodysostosis

Source: GeneReviews — "Pycnodysostosis"

Clinical Guidance

In the case of general anesthesia, consideration should be given to the possibility of difficult intubation prior to scheduling anesthesia. Bisphosphonate therapy is contraindicated due to underlying osteoclast dysfunction in pycnodysostosis.

Source: GeneReviews — "Pycnodysostosis"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Pycnodysostosis"