Pycnodysostosis (Online Mendelian Inheritance in Man number – 265800) is a rare autosomal recessive disorder with an estimated prevalence of 1 to 1.7 per million. The disorder is caused by a homozygous or compound heterozygous mutation in cathepsin K (CTSK), which is a lysosomal cysteine protease that is highly expressed in osteoclasts. CTSK is involved in the degradation of bone matrix proteins.
When to suspect? What are the clinical features?
Pycnodysostosis is characterized by dysmorphic facial features (broad forehead, small chin), a short stature, acroosteolysis, osteosclerosis with increased
bone fragility, and delayed closure of cranial sutures with persistence of an open fontanel and wormian bones. Patients may present during infancy with
pathological features or in childhood with short stature. Sometimes the condition is not detected until adulthood, usually as a result of a fracture or a
A child presenting with proportionate short stature, dental anomalies and characteristic broadening of terminal phalanges leads to clinical suspicion of
How is the disease diagnosed?
Radiographs are characteristic. Radio-opacity of all bones is increased because of increased density of the trabecular bone but not the cortices. Typical
hand features are brachydactyly, acro-osteolysis of distal phalanges, wide, open fontanelle, wormian bones. Ribs are broad, thick, and dense. Clavicles may
range from being aplastic to normal. Long bones are slender with over-modelled diaphysis. Clinical and radiological findings are diagnostic. Some cases may
be mis-diagnosed as osteopetrosis. There is no other biochemical diagnostic test other than mutation detection by gene sequencing.
What is the treatment?
No specific treatment for the disorder has been described. Short stature is a significant complaint and documented final heights of patients are below 150
cm for boys and 130–134 cm for girls. Recently, growth hormone therapy has shown positive effect on the linear growth. Almost half of affected patients
have a growth hormone deficiency but all have low IGF-1 levels, and administration of growth hormone results in a satisfactory elevation in IGF-1. Patients
should be followed for orthopedic complications and surveillance for neurological complications which are rare. Orthodontic management is required for all.
Maintenance of oral hygiene and regular dental care are key to preventing oral complications. Postextraction osteomyelitis can appear due to increased bone
density, and risk factors should be carefully addressed while planning tooth extraction and other surgeries.
Rarely, hepatosplenomegaly and hematological complications are reported similar to osteopetrosis.
What are the implications for the relatives of the patient?
Pycnodysostosis is an autosomal recessive disorder. Sibling of an affected individual has 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. Mutation detection in the proband by DNA sequencing of CTSK gene is
necessary for providing prenatal diagnosis. Families with consanguinity should be offered carrier testing and genetic counseling to the members of extended
Pycnodysostosis is not a life threatening disease. In the current era of advanced molecular research a specific treatment for the disorder may be
established in the future to prevent complications and improve quality of life for patients. The understanding of function of CTSK gene has lead to the new
therapies of osteopososis which means decreased bone density which is opposite of the manifestations of pycnodysostosis.