Cleidocranial Dysplasia in a Young Girl

LETTERS TO THE EDITOR

Cleidocranial Dysplasia in a Young Girl

mandibular lingual arches were given to maintain space mesial to first molars i.e. by space maintainers, thus allowing dental arch integrity and alveolar growth.

Sir, Cleidocranial dysplasia is an autosomal dominant trait, with defective CBFA1 (core binding factor) gene on 6p21 chromosome. RUNX2 is an osteoblast specific transcription factor, that demonstrates normal osteogenesis and odontogenesis. RUNX2 through (core binding factor CBFA1) performs master transcription (bone formation). RUNX2 comprises of 220 kb protein with exons (V, X, XI), belonging to RUNT domain gene family (RUNX-1,2,3). It maintains dental lamina formation during tooth calcification, differentiates cells of osteoblastic lineage. RUNX2 binds to osteoblast specific factor, cis-acting domain (OSE2). CBFA1 binds to promoter regions of osteocalcin, type-1 collagen, osteopontin and Matrix Metalloproteins (MMPs).1 Cleidocranial dysplasia or dysostosis is a diagnosed dental and clavicular defect, inherited as an autosomal dominant defect of CBFA1 gene on chromosome 6p21. Clavicles are malformed uni/bilaterally with drooping shoulders and neck lengthening. Clinically frontoparietal prominence, depressed nasal bridge, ocular hypertelorism and secondary ossification of wormian bones are typical.2 Cleft palate is common among retained decidous teeth and results in failure of erupted permanent teeth. Mandibular lesions are prognathic with coarse trabeculation of ascending ramus, sharpened coronoid process. Maxilla presents with hypolastic, thin zygomatic arch (vertical maxillary growth).2 Other features include midface hypoplasia, quarter moon physiognomy, supernumerary teeth etc.3,4

A major issue was maintenance of the arch length till eruption of all permanent teeth. To control the arch length, specially designed lower lingual arch and upper palatal arch was given. Beside controlling arch space, it also facilitated in pulling impacted teeth with the help of buttons and elastics. Erupted teeth were later bracketed with 0.022 brackets with Roth prescription leveled and aligned with normal wire sequence. Genomic profile (CBFA1) of cleidocranial dysostosis is RUNX2 dependant for bone mineralization and odontogenesis. Developmental anomalies i.e. germination, microdontia, and skeletal high arched palate, midface hypoplasia are common findings among cleidocranial cases. CBFA1 gene is essential for Sonic Hedgehog (SSh) expression for enamel knot formation. Dental follicle presents with preodontoblast and cementocytes, among periodontal bone attachement.5 Enamel knot genes (p21) among CCD are suppressed, effecting profile of Sonic Hedgehog (SSh) among mandibular molars, compared to healthy maxillary teeth.6 RUNX type-2, is expressed at crown

Figure 1: Preoperative profile (supernumerary teeth).

A 12-year-old female reported to orthodontic department, Altamash Institute of Dental Medicine, Karachi, with retained decidous teeth. Intraoral examination showed mixed dentition, with erupted maxillary central incisors and first molars, and mandibular incisors and first molars bilaterally. Molar relationship was class I with anterior open bite. Orthopantomogram (OPG) radiograph presented with supernumerary teeth and developing permanent tooth buds. Malformed clavicles, midfacial hypoplasia and frontoparietal bossing were seen along with supernumerary and retained teeth. Decidous and supernumerary teeth were extracted. Permanent teeth close to alveolar ridge were provided with orthodontic buttons to facilitate their eruption. Maxillary and 664

Figure 2: Gross clinical presentation.

Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (10): 664-666

Letters to the editor

development i.e. bell stage of developing dental follicle differentiating into pulp cells and odontoblasts.6 Patients with dental surgical and orthodontic management require rehabilitation of function, phonetics, and aesthetics. Psychosocial impact for individuals with genetic disorders, require maintenance of dental armamentarium. Thus early treatment intervention among cleidocranial dysplasias in the young is a fundamental health aspect.

REFERENCES 1.

Bone pathology, Chapter 14. In: Neville BW, Damm DD, Allen CM, Bouqout JE. A textbook of oral and maxillofacial pathology. 2nd ed. WB Saunders 2002, 538-90.

2.

Shui C, Spelsberg TC, Riggs BL, Khosla S. Changes in RUNX2/ CBFA1 expression and activity during osteoblastic differentiation of human bone marrow stromal cells. J Bone Miner Res 2003; 18: 213-21.

3.

Golan I, Baumert U, Hrala BP, Mubig D. Early craniofacial signs of cleidocranial dysplasia. Int J of Pediatr Dent 2004; 14:49-53.

4.

Richardson A, Denssen FF. Facial and dental anomalies in cleidocranial dysplasia: a study of 17 cases. Int J Pediatr Dent 1994; 4:225-31.

5.

Feldman GJ, Robin NH, Brueton LA, Robertson E, Thompson EM, Bartelt JS, et al.. A gene for cleidocranial dysplasia maps short arm chromosome 6. Am J Hum Genet 1995; 56:938-43.

6.

Jiang H, Sodek J, Karsenty G, Thomas H, Ranly D, Chen J. Expression of core binding protein factor OSF2/CBFA1 and bone sialoprotein in tooth development. Mech Dev 1999; 81:169-73.

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DR. SALIK RASOOL, DR. MUHAMMAD HASNAIN SAKRAN, DR. FARHAT BASHIR AND DR. SARA GARDEZI

Correspondence: *40/B, First East Street, DHA, Phase-I, Karachi. E-MAIL: [email protected]

The WHO STEPwise Approach to Stroke Surveillance Sir,

Stroke is the second leading cause of death globally.1 Fifty lac eighty thousand (5.8 million) people died of stroke worldwide in 2005, and roughly two-thirds of these deaths occurred in developing countries like Pakistan. Compared to western countries, stroke rates in middle aged people (30-69 years) are 5-10 times higher in developing countries such as Pakistan.2,3 It is estimated that the number of deaths from stroke will rise to 6.3 million in 2015 and 7.8 million by 2030. Most of these stroke-related deaths will occur in poor countries of the world.2,4,5 By 2050, it is anticipated that 80% of strokes will occur in developing countries.4,5 With an aging Pakistani population, the burden of stroke is likely to rise in Pakistan in the coming years. Many basic epidemiological questions regarding stroke in Pakistan remain unanswered. There are no population-based

epidemiological data about stroke incidence, mortality, stroke-related disabilities, functional status or case fatality rates available from Pakistan. Existing data are limited to small hospital-based studies and do not give any indication of the magnitude or distinct characteristics of the stroke problem in the Pakistani population. The most reliable data on the prevalence of stroke risk factors among the general population are based on the National Health Survey of Pakistan (NHSP), a nationally representative population-based survey conducted from 1990-1994. The NHSP data highlights the magnitude of the public health burden of different stroke risk factors such as hypertension, diabetes, obesity, cardiovascular disease and smoking in Pakistan. The World Health Organization (WHO) is supporting its member countries in their efforts to address the problems related to an ageing population, especially related to the surveillance of the major noncommunicable diseases like stroke. This will enable these countries to assess the magnitude and profile of the burden of these diseases, and to facilitate the design of interventions and to monitor their effectiveness. To facilitate this process, WHO has developed a STEPwise approach to stroke surveillance, which provides a framework for data collection and comparison between and within populations. A detailed manual was developed and is accessible at http://www.who.int/ ncd_surveillance/steps/stroke/en/. Neurologists and physicians who take care of stroke patients can apply to the International Coordinating Committee (ICC) for participation in a WHO STEPS stroke surveillance study. Financial support is available to participants. The details of the application process are on the above-mentioned website. We must encourage our Pakistani neurologist colleagues to consider participation in this project to help increase our understanding about stroke and to develop strategies that will decrease stroke burden in Pakistan.

REFERENCES 1.

Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: the results of the Global Burden of Disease Study. Lancet 1997; 349:1269-76.

2.

Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol 2007; 6:182-7.

3.

Bonita R, Beaglehole R. Stroke prevention in poor countries: time for action. Stroke 2007; 38:2871-2.

4.

Feigin VL. Stroke in developing countries: can the epidemic be stopped and outcomes improved? Lancet Neurol 2007; 6:94-7.

5.

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11):e442.

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DR. MUHAMMAD U. FAROOQ*, DR. ABDUL HAFEEZ CHAUDHRY, DR. KHALID AMIN AND DR. ARSHAD MAJID

Correspondence: *Department of Neurology and Ophthalmology Michigan State University East Lansing, MI 48824 , USA E-MAIL: [email protected]

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Letters to the editor

Vitamin D Deficiency Osteomalacia: the Continuing Challenge

in Asians, who, therefore, need more prolonged exposure to sunlight to give a similar response to Caucasians. Those at risk of nutritional vitamin D deficiency include the elderly, those living indoors or having a covered-up style of dress, especially darkskinned individuals and pregnant women and sun screen usage. Variation in vitamin D requirements could arise from genetic differences in vitamin D processing. A relationship between bone density and vitamin Dreceptor genotype is consistent with this possibility.

Sir, Vitamin D deficiency was first noted among the immigrant Asians including Pakistanis in the UK during the early 1970s. It was assumed that people living in Pakistan would have serum 25-hydroxycholecalciferol (25-OHD) concentrations well within the normal range, because of the abundant supply of ultraviolet light. The expression of vitamin D deficiency after immigration to UK was assumed to be an environmental and not a genetically determined characteristic.1 At that time, an abnormality in the metabolism of 25-OHD was not suspected. However, in 1997, it was demonstrated that 25-OHD metabolism may be altered in Asian Indians living in Southern United States. The investigators found evidence of increased production of inactive metabolite of vitamin D; 24, 25(OH)2D in Asians resulting from significantly increased activity of the enzyme synthesizing, compared to the active metabolite; 1, 25 (OH)2 D hydroxylase.2

Education of primary care physicians involved in the management of these patients is also important. Physicians in Pakistan tend to give calcitriol (1, 25 (OH)2 D) too readily to these patients with rickets or osteomalacia, before excluding nutritional osteomalacia or malabsorption. It is even more important to exclude a nutritional component in Pakistan than in West, because nutritional deficiency is so common. A failure to respond to oral or parental vitamin D suggests some form of vitamin D resistance. Calcitriol is not an entirely benign agent. Its use could cause hypercalcemia and renal damage. Further studies are needed to fully understand the pathophysiology of vitamin D deficiency in the South Asian population, so that appropriate preventive strategies can be introduced. The continuing prevalence of vitamin D deficiency in our population, particularly among adolescents, warrants immediate action. An effective preventive policy is long overdue.

We have identified a high incidence of vitamin D deficiency in healthy volunteers. In addition, significant vitamin D deficiency has been identified in ambulatory care setting.3,4 Patients frequently have typical presentation with poor nutritional history, lack of sunlight exposure, and low socioeconomic status, which are contributory factors. But, there are groups of patients as well as healthy volunteers in which vitamin D deficiency is difficult to explain, as there seem to be no associated risk factors. Some of them presented with florid osteomalacia including bowing deformity. It is difficult to exclude the sporadic form of vitamin D dependent osteomalacia type I, which has been described less often in late childhood and adolescence. However, the classical biochemical abnormality in such cases is normal 25-OHD concentration and lack of circulating 1, 25 (OH)2 D, which is usually not measured due to non-availability of the test.

REFERENCES 1.

Vaishnava H, Rizvi SN. Vitamin-D deficiency osteomalacia in Asians. Lancet 1973; 2:621-2.

2.

Awumey EM, Mitra DA, Hollis BW, Kumar R, Bell NH. Vitamin-D metabolism is altered in Asian Indians in Southern United States: a clinical research center study. J Clin Endocrinol Metab 1998; 83: 169-73.

3.

Lubna Z, Aysha HK, Abdul J. Vitamin D deficiency in ambulatory patients. JPMA 2008; 58:482-4.

4.

Aysha HK. Vitamin D deficiency: Are we still ignoring the evidence? JPMA 2008; 58:482-4.

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DR. AYSHA HABIB KHAN*, DR. ABDUL JABBAR, DR. REHMAN BAIG, DR. NAEEM-UL-HAQ AND ROGER A.L. SUTTON

Department of Pathology and Medicine The Aga Khan University Hospital , Karachi

It is important that these cases be identified at an early stage, so that bone abnormalities can be prevented. It is also very important to make people aware of the nutritional value of foods and the value of regular exposure to sunlight. The dose of ultraviolet radiation needed to produce a minimal erythemal dose is higher

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Correspondence: *116 A/II, 16th Street, Off Mohafiz, Phase-VI , DHA Karachi E-MAIL: [email protected]

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