Pignodisóstosis (pycnodysostosis) CTSK Gen.
The pignodisóstosis is a rare disorder characterized by bone deformity skull, jaw and phalanges, osteosclerosis, bone fragility and short stature. The disease is discovered at variable ages from 9 months to 50 years. In general, the diagnosis is established during childhood but sometimes the disease is not detected until adulthood, usually as a result of a fracture or a routine exam.
Signs and symptoms include frequent osteosclerosis, short stature or dwarfism, acroosteolysis of the distal phalanges, fragile bones associated with spontaneous fractures and dysplasia of the clavicles. Affected individuals may have cranial malformations features like bulky skull with bones wormian presence and persistence of the anterior fontanelle, and small jaw. Dental anomalies can be observed as tooth decay, badly implemented, pointed or tapered shape, and delayed tooth eruption. Sometimes nails are irregular and brittle. Very rarely, the disease is associated with anemia, hepatosplenomegaly, blood disorders, respiratory distress and sleep apnea.
This process is due to mutations in the gene CTSK, located on the long arm of chromosome 1 (1q21). The protein encoded by this gene is a lysosomal cysteine proteinase, involved in bone remodeling and resorption. This protein is a member of the peptidase family proteins C1, which is predominantly expressed in osteoclasts. However, the encoded protein is also expressed in a significant fraction of breast cancers, which could contribute to tumor invasiveness.
Mutations in the gene CTSK, cause the demineralized bone region surrounding the individual osteoclasts increases, causing among other symptoms, short stature, bone fragility, fracturas spontaneous, skull and dental malformations.
The pignodisóstosis is inherited as an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with pignodisóstosis, by complete PCR amplification of the exons of the gene CTSK, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).