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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 [1]. Pyknodysostosis is rare, and some cases have been linked with consanguinity [2]. Males are predominantly affected, while the onset of the disease is often observed in children and young adults [3].

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 [4] [5]. Further deformities in the oral cavity include macroglosia and a ridged or high-arched palate [6].

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 [7]. There are variant genotypes of the condition that present with more severe, earlier-onset symptoms [8]. 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.

Hemophilia A
  • The royal hemophilia. Sci. Am. 213, 88–95 (1965). 25 Loftus, L.S. & Arnold, W.N. 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.[oadoi.org]
Short Stature
  • The short stature is variable but moderate (1.35m to 1.50m).[orpha.net]
  • 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]
  • Pycnodysostosis, an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature, maps to chromosome 1q21.[ncbi.nlm.nih.gov]
  • 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]
  • Patients with pycnodysostosis, a rare skeletal dysplasia, present with bone abnormalities such as short stature, acroosteolysis of distal phalanges, and skull deformities.[ncbi.nlm.nih.gov]
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]
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]


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 [1]. 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 [9].
  • 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 [10]. Molecular testing to detect the mutation in the gene coding for CTSK confirms the diagnosis [10].


  • This article outlines the clinical and radiographic characteristics of this condition based on the clinical case described and proposes an approach regarding the best form of treatment.[oadoi.org]
  • Risk of infection and/or nonunion after such a surgical procedure was considered too great, and therefore the possibility of treatment by distraction osteogenesis of the maxilla was evaluated.[ncbi.nlm.nih.gov]
  • Management and treatment Management is symptomatic and multidisciplinary. It includes orthopedic monitoring, treatment of fractures, of which consolidation is sometimes slow, and static vertebral surveillance to detect frequent spondylolisthesis.[orpha.net]


  • Prognosis The prognosis is favorable; the disease is not progressive. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • The calvaria is disproportionately large, due to bulging frontal and occipital bones. [2], [3] The prognosis of the disease is good and no other more serious systemic alteration has been noted. [3] The purpose of this article was to report a case of a[jisppd.com]
  • The prognosis of this disease is good and no serious systemic alterations have been noted.[jiaomr.in]
  • Child patients should receive special dental care, particularly preventive treatment because of the group of mouth alterations described, in addition to periodic follow-up of their growth and craniofacial development. 11 The prognosis of the disease is[synapse.koreamed.org]


  • Etiology Pycnodysostosis is due to mutations in the gene encoding cathepsin K (localized to 1q21), a lysosomal enzyme secreted by osteoclasts, which allows the division of proteins of the bone matrix (collagen type I, osteonectin or osteopontin).[orpha.net]
  • Etiology Pyknodysostosis is an autosomal recessive congenital abnormality resulting in mutations in the CTSK gene at 1q21, which codes for cathepsin K.[radiologykey.com]
  • Etiology MNS is caused by gain of function mutations in the gene FLNA (Xq28) that encodes the actin-binding cytoskeletal protein filamin A.[orpha.net]


  • Summary Epidemiology It is very rare, the exact prevalence is unknown but it is less than 1/100,000. Clinical description The disease is discovered at variable ages, ranging from 9 months to 50 years.[orpha.net]
  • Summary Epidemiology To date, less than 70 cases with MNS have been documented. MNS is a disorder essentially limited to females as it is lethal in males. Survivorship in males is possible due to mosaicism.[orpha.net]
Sex distribution
Age distribution


  • Pathophysiology Cathepsin K is a lysosomal cysteine protease that plays a key regulatory role in bone metabolism, abnormalities of which interfere with bone resorption and remodeling.[radiologykey.com]
  • In a format designed for quick reference, it provides complete information on the symptoms, pathophysiology, diagnosis, and treatment of all common and rare bone and mineral disorders.[books.google.com]


  • Craniotomy was needed to evacuate the haematoma and prevent mortality. Extradural haematoma in this group of patients is rare, ours being the second case reported in literature.[ncbi.nlm.nih.gov]
  • Such patients must be placed under an oral hygiene prevention scheme, a treatment plan must be accurately designed and the patient must be constantly motivated.[moh-it.pure.elsevier.com]



  1. Motyckova G, Fisher DE. Pycnodysostosis: role and regulation of cathepsin K in osteoclast function and human disease. Curr Mol Med. 2002;2(5):407-421.
  2. Ramaiah KKK, George GB, Padiyath S, Sethuraman R, Cherian B. Pyknodysostosis : report of a rare case with review of literature. Imaging Sci Dent. 2011;41(4):177–181.
  3. Kamak H, Kamak G, Yavuz I. Clinical, radiographic, diagnostic and cephalometric features of Pyknodysostosis in comparison with Turkish cephalometric norms: A case report. Eur J Dent. 2012;6(4):454–459.
  4. Fleming KW, Barest G, Sakai O. Dental and facial bone abnormalities in pyknodysostosis: CT findings. AJNR Am J Neuroradiol. 2007;28 (1)132-134.
  5. Moniz N, Queiroz EA, Freitas RR, Felix VB. Mandibular reconstruction with autogenous graft in patient presenting pyknodysostosis: case report. J Oral Maxillofac Surg. 2006;64(8):1292-1295.
  6. Schmitz JP, Gassmann CJ, Bauer AM, Smith BR. Mandibular reconstruction in a patient with pyknodysostosis. J Oral Maxillofac Surg. 1996;54(4):513-517.
  7. Xue Y, Cai T, Shi S, et al. Clinical and animal research findings in pycnodysostosis and gene mutations of cathepsin K from 1996 to 2011. Orphanet J Rare Dis. 2011;6:20.
  8. Arman A, Bereket A, Coker A, et al. Cathepsin K analysis in a pycnodysostosis cohort: Demographic, genotypic and phenotypic features. Orphanet J Rare Dis. 2014;9:60.
  9. Hunt NP, Cunningham SJ, Adnan N, Harris M. The dental, craniofacial, and biochemical features of pyknodysostosis: a report of three new cases. J Oral Maxillofac Surg. 1998;56(4):497-504.
  10. Mujawar Q, Naganoor R, Patil H, Thobbi AN, Ukkali S, Malagi N. Pyknodysostosis with unusual findings: a case report. Cases J. 2009;2:6544.

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Last updated: 2018-06-22 09:30