Clinical characteristics: Pycnodysostosis is characterized by short-limbed short stature, typical facial appearance (convex nasal ridge and small jaw with obtuse mandibular angle), 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. Additional features include dental and nail anomalies. Intelligence is typically normal with mild psychomotor difficulties reported in some individuals.
Diagnosis/testing: The diagnosis of pycnodysostosis can be established in a proband with characteristic clinical and radiographic features and/or biallelic pathogenic variants in CTSK identified by molecular genetic testing.
Management: Treatment of manifestations: Growth hormone therapy; environmental or occupational modifications as needed; orthopedic management of fractures and scoliosis; craniofacial and neurosurgical management as required for cleft palate, craniosynostosis, maxillary and mandibular hypoplasia; pulmonology and sleep medicine specialist management of obstruction sleep apnea; consultation with expert anesthetist prior to any planned surgery; dental and orthodontic care for dental anomalies; standard management per ophthalmologist for vision concerns.
Surveillance: Annual physical examination including assessment for scoliosis, asymmetry, frequency of fractures, weight and nutrition, and psychological assessment; polysomnography every two years; annual evaluation with specialist dentist and ophthalmologist.
Agents/circumstances to avoid: If general anesthesia is needed, consider the possibility of difficult intubation prior to scheduling anesthesia.
Pregnancy management: In individuals with a small pelvis, delivery by cæsarean section should be considered. However, each individual should be assessed by an obstetrician and anesthetist familiar with skeletal dysplasia.
Genetic counseling: Pycnodysostosis is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CTSK pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the CTSK pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
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