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Table of Contents
Year : 2021  |  Volume : 70  |  Issue : 4  |  Page : 258-261

Osteosclerotic bone disorder - Pyknodysostosis

1 Department of Anatomy, Government Medical College, Palakkad, Kerala, India
2 Department of Anatomy, All India Institute of Medical Sciences, Nagpur, Maharashtra, India
3 Department of Radiodiagnosis, SRM Trichy Medical College Hospital and Research Centre, Tiruchirappalli, Tamil Nadu, India

Date of Submission29-Mar-2020
Date of Acceptance30-Sep-2021
Date of Web Publication21-Dec-2021

Correspondence Address:
Dr. N Vinay Kumar
Department of Anatomy, Government Medical College, NH.47, East Yakkara, Kunnathurmedu, Palakkad - 678 013, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JASI.JASI_54_20

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Pyknodysostosis is an autosomal recessive osteoclastic dysfunction characterized by generalized hyperostosis and short stature which has mere 10 cases reported from India out of 133 globally reported cases. This rare disorder is due to defective lysosomal cysteine protease cathepsin K in chromosome 21. A male child of 11 years underwent radiological investigation for stunted growth. Examination revealed less height for age, retarded mandibular growth, dysmorphic facial growth, and proportionately short fingers. Radiological findings showed generalized osteosclorosis, hypoplastic paranasal air sinuses, spool-shaped dorsolumbar vertebral bodies, acro-osteolysis of terminal phalanges, and scalloped acetabulum with increased bone density. Management of child should be aimed at correcting anemia and primary prevention of fractures. The postnatal craniofacial development needs to be monitored. Long-term management should aim at genetic mapping and therapy with bone marrow transplantation.

Keywords: Acro-osteolysis, osteosclerosis, pyknodysostosis

How to cite this article:
Kumar N V, Gugapriya T S, Arun GT. Osteosclerotic bone disorder - Pyknodysostosis. J Anat Soc India 2021;70:258-61

How to cite this URL:
Kumar N V, Gugapriya T S, Arun GT. Osteosclerotic bone disorder - Pyknodysostosis. J Anat Soc India [serial online] 2021 [cited 2022 Jul 3];70:258-61. Available from: https://www.jasi.org.in/text.asp?2021/70/4/258/333195

  Introduction Top

Pyknodysostosis, also known as osteopetrosis acro-osteolytica or Toulouse–Lautrec syndrome, is a rare autosomal recessive bone disorder of osteoclast dysfunction, characterized by short stature and generalized osteosclerosis or hyperostosis with acro-osteolysis of terminal phalanges.[1] This condition has an incidence of 1.7 per 1 million births and shows equal sex distribution with a significant relation to parental consanguinity. So far, medical literature has 133 reports of this condition, of which 10 have been reported from India.[1],[2],[3]

The disorder is characterized by postnatal onset of proportionate dwarfism, repeated respiratory infections, sleep apnea, and diffuse generalized osteosclerosis with increased incidence of long bone fractures after minimal trauma. There is increased bone density with thickened cortex and narrow medulla. Intellectual and sexual development and lifespan are found to be usually normal in affected individuals.[1],[2],[4],[5]

Typical dysmorphic facies, abnormal dentition, and axial skeletal abnormalities have been described. The appendicular skeletal abnormalities with hypoplastic clavicle and short broad hands with total or partial acro-osteolysis of terminal phalanges were reported as specific features of this condition.[1],[2],[4],[5],[6]

  Case Presentation Top

An male child aged 11 years with complaints of delayed milestones and reduced height was investigated in the department of radiodiagnosis. No history of parental consanguinity or repeated bone fractures was noted.

On examination, the child was short statured for his age, with a measured height of 98 cm. The fingers were proportionately short with wrinkled skin over the dorsum of distal fingers and flat, grooved nails. A large head with hypoplastic face, depressed nasal bridge, Fronto-occipito-parietal bossing, persistent fontanelles, and small mandible with prognathism were noted. The oral cavity showed crowding of teeth and high arched palate. The chest wall was observed to have prominent sternum with barrel-shaped deformity. Accentuated lumbar lordosis was observed. Hypoplasia of fingers was also noted.

On radiological examination, almost all the bones showed increased bone density with diffuse osteosclerosis. The long bones were seen with thickened cortex and narrow medulla [Figure 1]. Lateral cephalogram showed hypoplastic nasal bones and paranasal air sinuses. The mandible was hypoplastic, and the gonial angle was grossly obtuse (flattened) with prognathism. The mandibular ramus, condyle, and condylar notch were narrow [Figure 2]. The calvaria and skull base were thick with persistent fontanelles with wide-open lambdoid sutures. The bony volume of sella turcica was increased with reduced size of hypophyseal fossa [Figure 3]. Radiograph of the cervicothoracic region revealed hypoplastic clavicle with aplasia of acromial end and normal cardiac outline [Figure 4]. The dorsolumbar spine showed spool-shaped vertebral bodies, prominent in the anterior aspect [Figure 5]. Acro-osteolysis of terminal phalanges in most of the fingers was observed in both hands [Figure 6]. The roentgenogram of the pelvis showed scalloped outline of the acetabulum with increased bone density [Figure 7]. No previous signs of fracture were visible in the radiographs of the long bones. The child was advised genetic analysis to confirm the diagnosis.
Figure 1: Increased bone density with diffuse osteosclerosis (red arrows) and narrow medullary cavity (blue arrows)

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Figure 2: Hypoplastic paranasal air sinuses (red arrows) and nasal bone (blue arrow). Hypoplastic mandible with flattened gonial angle (yellow arrow)

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Figure 3: Thick cranial vault and skull base (red arrows), persistent fontanelle (green arrows), wide-open lamdoid suture (yellow arrow), and reduced size of hypophyseal fossa (pink arrow)

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Figure 4: Hypoplastic clavicle with aplasia of acromial end (red arrow)

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Figure 5: Spool-shaped dorsolumbar vertebral bodies (red arrows)

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Figure 6: Acro-osteolysis of terminal phalanges (red arrows)

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Figure 7: Scalloped outline of the acetabulum (red arrows) with increased bone density of pelvis

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  Discussion Top

Pyknodysostosis is an autosomal recessive osteoclast dysfunction exhibiting equal gender distribution and documented parental consanguinity in only 38% of reported cases.[7],[8] Similar to the present case, these cases present at an early age with short stature and open fontanelles. The presentation at later ages may be due to fractures, resulting from minimal or moderate trauma.[9],[10]

A genetic defect on chromosome 1q21 is claimed as the main factor, resulting in increased sclerosing activity. Cathepsin K (CTSK), a lysosomal cysteine protease which is implicated in osteoclast-mediated bone resorption and remodeling, undergoes mutational changes resulting in reduced expression in osteoclasts. The enzyme degrades type 1 collagen, which constitutes 95% of organic bone matrix. The bones become abnormally dense and brittle due to insufficient resorption by osteoclasts.[11]

The compression of pituitary gland due to increased bone volume of sella turcica resulting in deficient production of growth hormone was reported as probable reason for short stature which is observed as the most common characteristic feature of this condition.[12],[13] The typical features in facial, axial, and appendicular skeleton as documented previously were observed in the present case also.[12]

Some of the additional features reported by studies, such as the presence of wormian bones in sutures, incomplete segmentation of vertebrae, coxa valga and abnormal radioulnar articulation, and hepatosplenomegaly, were not observed in our case report.[1],[12]

In the process of clinical diagnosis, this condition needs to be differentiated from the comparatively common bone disorders such as osteopetrosis, cleidocranial dysplasia, and idiopathic acro-osteolysis by observation of other specific characters of those conditions. In osteopetrosis, the bone marrow may be absent without increased bone density. Signs of cranial nerve compression such as facial paralysis and deafness may exist. The hands, feet, clavicles, gonial angles, maxilla, and skull vault are normal without stunted growth or multiple fractures or diffuse osteosclerosis. Cleidocranial dysplasia/dysostosis looks similar to pyknodysostosis due to the presence of clavicular aplasia and alterations of skeletal bone membranes. The bone density and height are normal with the absence of diffuse osteosclerosis. Cranium and clavicle are involved but spare mandible and phalanges. In idiopathic acro-osteolysis, there is typical appearance with hypotelorism, exophthalmos, an upturned nose, and acute mandibular angle without increased bone density.[1],[3],[4],[6],[8],[9]

Diagnosis of this condition at an early age, after considering other possible disorders, will help to plan a suitable treatment to improve the patient's quality of life. The diagnosis is primarily based on clinical features and radiographs, but CTSK gene mutation analysis is the confirmatory test.[3] The management for this condition is mainly supportive treatment considering the growth retardation and craniofacial developmental abnormalities. It should also aim at correcting anemia and primary prevention of fractures. In addition to bone marrow transplantation for providing normal osteoclasts and their targeted enzymes, gene replacement strategies are drawing more attention.[4]

The prognosis is good with normal life expectancy and without much serious systemic disabilities.[3] This case is being presented for its rarity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ramaiah KK, George GB, Padiyath S, Sethuraman R, Cherian B. Pyknodysostosis: Report of a rare case with review of literature. Imaging Sci Dent 2011;41:177-81.  Back to cited text no. 1
Fleming KW, Barest G, Sakai O. Dental and facial bone abnormalities in pyknodysostosis: CT findings. AJNR Am J Neuroradiol 2007;28:132-4.  Back to cited text no. 2
Mujawar Q, Naganoor R, Patil H, Thobbi AN, Ukkali S, Malagi N. Pyknodysostosis with unusual findings: A case report. Cases J 2009;2:6544.  Back to cited text no. 3
Sudarshan R, Vijayabala GS. Pycnodysostosis – A review. Southeast Asian J Case Rep Rev 2012;1:42-5.  Back to cited text no. 4
Yadav BB, Kumawat DC. Pyknodysostosis: Report of a rare disorder. J Indian Acad Clin Med 2015;16:258-60.  Back to cited text no. 5
Pereira DA, Aytés LB, Escoda CG. Pycnodysostosis. A report of 3 clinical cases. Med Oral Patol Oral Cir Bucal 2008;13:633-5.  Back to cited text no. 6
Costa AF, Lopes SO, Almeida SM, Steiner C. Pycnodysostosis: An early case report with emphasis on the radiographic findings. Int J Dent Sci 2006;3:2.  Back to cited text no. 7
Fonteles CS, Chaves CM Jr., Da Silveira A, Soares EC, Couto JL, de Azevedo MF. Cephalometric characteristics and dentofacial abnormalities of pycnodysostosis: Report of four cases from Brazil. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:83-90.  Back to cited text no. 8
Landa S, Esteban S, Montes E, Santamaria J, Vitoria A, Santolaya JM. Maxillofacial alterations in a family with pycnodysostosis. Med Oral 2000;5:169-76.  Back to cited text no. 9
Ferguson JW, Brown RH, Cheong LY. Pycnodysostosis associated with delayed and ectopic eruption of permanent teeth. Int J Paediatr Dent 1991;1:35-8.  Back to cited text no. 10
Motyckova G, Fisher DE. Pycnodysostosis: Role and regulation of cathepsin K in osteoclast function and human disease. Curr Mol Med 2002;2:407-21.  Back to cited text no. 11
Alves N, Oliveira RJ, Deana NF, Sampaio JC. Morphological features of pycnodysostosis with emphasis on clinical and radiographic maxillofacial findings. Int J Morphol 2013;31:921-4.  Back to cited text no. 12
Soliman AT, Ramadan MA, Sherif A, Aziz Bedair ES, Rizk MM. Pycnodysostosis: Clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. Metabolism 2001;50:905-11.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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