Pyknodysostosis is a rare lysosomal storage disease that follows an autosomal recessive inheritance pattern. It typically involves multiple skeletal deformities, as well as dwarfism. Features can be observed both clinically and radiologically.
Pyknodysostosis is a genetic disease that is inherited with an autosomal recessive pattern. It is caused by a mutation in chromosome 1q21, which, in turn, leads to the production of a defective cystine protease, an enzyme found in lysosomes, called cathepsin K (CTSK), which normally breaks down type 1 collagen fibers. The end result of this process is dense, brittle bones . Pyknodysostosis is rare, and some cases have been linked with consanguinity . Males are predominantly affected, while the onset of the disease is often observed in children and young adults .
Clinically, the condition presents with dental abnormalities such as crowding due to persisting deciduous teeth, a tendency to form dental caries, dental abscesses, enamel erosion, hypercementosis and short dental roots  . Further deformities in the oral cavity include macroglosia and a ridged or high-arched palate .
Musculoskeletal signs include dwarfism, limb and digit anomalies, frequent fractures, poorly formed clavicles and craniosynostosis (premature closure of sutures in infants, resulting in abnormal skull shape). Moreover, other features that include respiratory problems, and Arnold-Chiari malformation, have been described . There are variant genotypes of the condition that present with more severe, earlier-onset symptoms . Of note, individuals who suffer from pyknodysostosis are not typically anemic, and this can help distinguish the disease from similar bone disorders such as osteopetrosis.
Entire Body System
- Short Stature
Pyknodysostosis is a rare, genetic, autosomal recessive condition characterized by short stature, generalized bone sclerosis, and oral manifestations such as maxillary atresia and an increase of the mandibular angle. [ncbi.nlm.nih.gov]
The short stature is variable but moderate (1.35m to 1.50m). [orpha.net]
Abstract: Patients with pycnodysostosis, a rare skeletal dysplasia, present with bone abnormalities such as short stature, acroosteolysis of distal phalanges, and skull deformities. [doi.org]
[…] pyknodysostosis [ pik″no-dis″os-to sis ] a hereditary syndrome of dwarfism, osteopetrosis, and skeletal anomalies of the cranium, digits, and mandible. pyk·no·dys·os·to·sis ( pik'nō-dis'os-tō'sis ), [TA] A condition characterized by short stature, delayed [medical-dictionary.thefreedictionary.com]
- Acute Intermittent Porphyria
Vincent van Gogh's illness: Acute intermittent porphyria? Brit. med. J. 303, 1589–1591 (1991). 26 O'Shea, J.G., Chopin's illness actually cystic fibrosis? Med. J. Aust. 147, 586–589 (1987). 27 Frey, J. Toulouse-Lautrec: A life. [oadoi.org]
- Failure to Thrive
[…] to thrive for evaluation. [dx.doi.org]
Case presentation An 11-year-old Indian boy from Bijapur district of Karnataka State was referred to the paediatric unit of the Al Ameen Medical College Hospital with history of short stature, dysmorphic facies and failure to thrive for evaluation. [ncbi.nlm.nih.gov]
It causes weakness, stunted stature, and failure to thrive. Bones appear dense on x-rays, and cerebral calcifications are seen; renal tubular acidosis is present, and RBC carbonic anhydrase activity is decreased. [merckmanuals.com]
- Bluish Sclerae
Clinical features of pycnodysostosis are short stature, fractures, large head with frontal and parietal bossing, open anterior fontanelle and cranial sutures, obtuse mandibular angle, prominent eyes with bluish sclerae, underdeveloped facial bones, dental [dx.doi.org]
- Retinal Pigmentation
Mitf or its related family members also are expressed in a variety of nonosteoclast cell types including melanocytes, mast cells, and retinal pigment epithelium ( 7 ). [dx.doi.org]
The diagnosis, as well as the evaluation of the extent of pyknodysostosis, relies mainly on the clinical picture, as well as on imaging modalities. The commonly used techniques are:
- X-rays - Findings may include delayed fontanelle and suture closure, skull bossing in the frontal and occipital bones, flat mandibular angle, beaked nose, paranasal sinuses lacking air spaces, osteosclerosis, short digits, aplastic phalanges and clavicles, distally widened femurs, and long bone fractures. There are also a number of spinal abnormalities such as pronounced lumbar lordosis, anomalous segmentation of vertebrae, especially in the cervical and lumbar regions, as well as sclerosis . Generally, the bones throughout the skeleton will have increased radio-opacity due to increased density.
- Computerized tomography (CT) scanning - This may show hypoplastic sinuses and slow skeletal maturation, seen as delayed bone age .
- Magnetic resonance imaging (MRI) - Bone thickening may also be visualized through this technique.
Histological analysis of bone is carried out, and may demonstrate features such as attenuated central canals in the Haversian system and abnormal medullary canals . Molecular testing to detect the mutation in the gene coding for CTSK confirms the diagnosis .
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