This condition is caused by mutations (changes) in the CTSK gene. This gene produces an enzyme called cathepsin K. The job of this enzyme is to breakdown certain substances in the body including bone proteins and certain types of collagen. Normally bone resorption will take place which refers to the breakdown of bone followed by the formation of new bone. In individuals with this condition, some of these materials are not completely broken down and build up in the lysosomes of the cell. When enough of these materials build up, they become toxic, affecting the cells and tissues of the body. This is what causes the symptoms associated with Pycnodysostosis.

The symptoms of this condition can vary from patient to patient and not all individuals with the condition will have all the symptoms listed below. Symptoms of Pycnodysostosis may include: 80%-99% of patients have these symptoms: • Abnormal fingernails • Abnormal pelvis bone ossification • Abnormal vertebral morphology • Abnormality of epiphysis morphology (abnormal shape of end part of bone) • Abnormality of the clavicle (abnormal collarbone) • Brachycephaly (short and broad skull) • Brachydactyly (short fingers or toes) • Delayed eruption of teeth • Frontal bossing • High forehead • Malar flattening (zygomatic flattening) • Midface retrusion (decreased size of midface) • Narrow palate (narrow roof of mouth) • Osteolysis (breakdown of bone) • Persistent open anterior fontanelle • Recurrent fractures • Short distal phalanx of finger (short outermost finger bone) • Short stature (decreased body height) • Short toes • Skeletal dysplasia 30%-79% of patients have these symptoms: • Abnormality of dental morphology (abnormal dental shape) • Blue sclerae (whites of eyes are a bluish-grey colour) • Bone pain • Proptosis (bulging eye) • Ridged nail (grooved nails) • Wormian bones (extra bones within cranial structures) 5%-29% of patients have these symptoms • Abnormal pattern of respiration • Abnormality of skin • Anaemia (low number of red blood cells or haemoglobin) • Cognitive impairment • Hepatomegaly (enlarged liver) • Hydrocephalus (too much cerebrospinal fluid in the brain) • Hyperlordosis (prominent swayback) • Kyphosis (hunched back) • Narrow chest • Osteomyelitis (bone infection) • Splenomegaly (increased spleen size)

This condition is caused by mutations (changes) in the CTSK gene.

Pycnodysostosis is diagnosed based on identifying characteristic symptoms, a detailed patient and family history, clinical evaluation and X-rays. The X-rays will show the characteristic bone changes that are associated with this condition. The diagnosis can be confirmed through molecular genetic testing which will show mutations in the CTSK gene in individuals with the condition.

There is no standardized treatment for this condition. Treatment is symptomatic and supportive, treating specific symptoms present in the individual and providing support for the patient and their family. Patients and their family may benefit from genetic counselling and psychosocial support is essential for the whole family. Patients will need orthopaedic care when they have a fracture. Specialized dental care should also be provided. Individuals with this condition should be evaluated before undergoing any procedures that require anaesthesia as they may have complications due to their abnormal jaw and mouth (palate).