Achondroplasia and periodontal disease

Abstract

Achondroplasia is a non-lethal form of chondrodysplasia. It is a disturbance of endochondral bone formation which results in characteristic dwarfism. It is transmitted as an autosomal dominant trait, with complete penetrance. De novo mutations cause up to 90% of cases. The mutation rate is estimated to be 0.000014 per gamete per generation. It is a rare disorder with a prevalence of 1:10,000 to 1:50,000 births worldwide. A young female patient suffering from achondroplasia reported with oral manifestations showing features of periodontitis, hypoplasia of the mid-face, deep periodontal pockets, and mobility of teeth. This case report highlights this rare anomaly and its oral manifestations.

INTRODUCTION

Achondroplasia is a disorder of bone growth that causes the most common type of dwarfism. It belongs to a group of disorders called chondrodystrophies or osteochondrodysplasias. It may be inherited as an autosomal dominant trait, which means that if one parent has achondroplasia, the infant has a 50% chance of inheriting the disorder and if both parents have the condition, the infant's chances of being affected increase to 75%. However, most cases appear as spontaneous mutations which mean that an achondroplastic child can have normal parents. Till date none of the cases of achondroplasia have been reported to have periodontal disease. This article presents a case of a female patient with achondroplasia and early development of periodontal disease.

CASE REPORT

A 31-year-old female patient diagnosed as suffering from achondroplasia had reported to the Department of Periodontics and Oral Implantology, Maulana Azad Institute of Dental Sciences, New Delhi, with the chief complaint of many loose teeth. Patient was born after a term uncomplicated pregnancy. Family history was unremarkable. The patient had history of vitamin D deficiency rickets when she was one year old and treatment was done for the same. The past dental history revealed that the deciduous teeth had erupted normally and the shedding was normal. The patient had a history of flap surgery with bone grafting in upper anterior region at the age of 27 years.

General examination

On general examination, the patient had short stature (127 cm height), long narrow trunk, short extremities, particularly in the proximal segments (rhizomelic shortening), bow legs (genu varum), short mid-face and maxilla, flattening of nasal bridge, and relatively broad forehead [Figure 1]. Extension and rotation were limited at the elbow. A thoracolumbar gibbus was present.

Figure 1.

Long trunk and relatively flattened nasal bridge

Intraoral examination

Intraoral examination revealed that the patient's oral hygiene was fair with a plaque score <1 (Sillness and Loe, 1964). The gingiva was erythematous and soft and associated with bleeding on probing. Full mouth probing depths, mobility and furcation involvement were recorded. Grade I mobile were 13, 14, 21, 23, 28, 33, 35, 37, 43, 45, 46, and 48; 22, 26, 34, and 47 were grade II mobile; and upper right lateral incisor was grade III mobile. There was grade II furcation involvement in relation to 36, 46, and 47. Generalized mucogingival problems were present. The following teeth were missing 15, 16, 17, 24, 25, 26, 31, 32, 41, and 42. Pathologic migration was present. The patient had Angle's Class III malocclusion with bilateral posterior cross-bite and narrow maxillary arch [Figure 2].

Figure 2.

Intraoral view

Radiographic findings

A skeletal survey was conducted for the patient. X-ray skull (lateral view) showed relatively broad forehead and flattening of nasal bridge, short maxilla and mid-face, and short base of skull. X-ray base of skull revealed short foramen magnum, which is a cardinal feature of achondroplasia. Anteroposterior (AP) spine view showed short pedicle and short interpediculate distance. Progressive narrowing of the lumbar region with posterior scalloping due to short pedicle suggestive of lumbar canal stenosis was seen on DL spine view. Pelvis (AP) view showed characteristic “champagne glass deformity” with squaring of iliac crests. A confirmatory scanogram was done which revealed bow legs causing genu varum deformity with tibial bowing.

Orthopantomogram (OPG): An OPG was done when the patient was 27 years old, which showed generalized bone loss in relation to all teeth. A 2^nd OPG was done at 31 years of age, which showed severe bone loss in maxilla indicating that periodontitis had progressed rapidly in four years. Mandible, on the other hand, showed slow and gradual progression of bone loss [Figures 3 and 4].

Figure 3.

OPG (2004)

Figure 4.

OPG (2008)

Investigations

Complete blood count of the patient was normal. Serum alkaline phosphatase was markedly raised (208 U/l).

Treatment

Phase I therapy was started in the patient which included full mouth scaling and root planing with detailed oral hygiene instructions. The patient was prescribed chlorhexidine digluconate mouth rinse (0.2%), twice daily. Upper right lateral incisor was extracted as it was grade III mobile with hopeless prognosis. Upper and lower removable partial dentures were delivered to restore function.

DISCUSSION

Achondroplasia is a non-lethal form of chondrodysplasia which means “without cartilage formation”. It is an autosomal condition with a birth prevalence of 1:10,000 to 1:50,000, and the most common form of skeletal dysplasia in humans. Up to 90% of cases represent de novo mutations.[1] The homozygous form of achondroplasia is usually fatal within the first few months of life because of the severe rib-cage deformity that results in respiratory insufficiency.[2] It is the heterozygous form that allows survival into adulthood. There is a disturbance in the division and maturation of growth plate chondroblasts causing a deficiency of chondroid and an inhibition of normal endochondral growth. The limb bones are affected, but the trunk is relatively normal.

The dentition of achondroplastic dwarfs is described usually being without abnormality. In some achondroplastics, a malocclusion has been described.[3] Stafne (1950) reported retarded eruption of many permanent teeth in a 30-year-old affected male.[4] Several odontostomatologic manifestations of achondroplasia have been previously reported, including skeletal and dental class III malocclusion, a narrow maxilla, macroglossia, and an open bite between the posterior teeth.[5] To date, any form of periodontitis has not been reported with achondroplasia, despite maxillary growth process being affected.

It is a genetic disorder that results in abnormally short stature. A gain-of-function missense mutation in the nucleotide 1138 (A-T), defined as G380R, in the locus gene encoding for the fibroblast growth factor receptor-3 (FGFR3) on chromosome 4p.16.3 has been reported in 97-98% of patients.[1] This leads to inhibition of chondrocyte proliferation in the growth plate.[6] FGFR3 gene provides instructions for making a protein called fibroblast growth factor receptor 3, which is a part of fibroblast growth factor receptors. This protein is involved in the development and maintenance of bone and brain tissue. It limits the formation of bone from cartilage (a process called calcification), particularly in the long bones. These proteins also play a role in the regulation of cell growth and division, determination of cell type, formation of blood vessels, wound healing and embryo development. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. Researchers believe that these mutations cause the protein to be overly active, which interferes with skeletal development and results in decreased endochondral ossification, inhibited proliferation of chondrocytes in growth plate cartilage, decreased cellular hypertrophy, and decreased cartilage matrix production.[1]

Though literature does not report any cases of achondroplasia associated with periodontal disease, the case presented here, showed early development of periodontal disease. The possible reason could be that defective FGFR3 might hamper the growth and function of fibroblasts, which are the predominant cells found in the periodontal ligament. A missense mutation in FGFR3 gene leads to impaired formation of FGFR3 protein, which can hamper the growth and function of periodontal fibroblasts. This case can be a gateway for further research on FGFR3 gene and its possible role in periodontal disease and health.

When the case reported, periodontal disease had already advanced and the patient had lost many teeth. With this case report, we stress the need for early referral of each achondroplastic patient to the periodontist. Regular oral health check-ups and timely intervention in these patients can help in prevention and lessening the morbidity of periodontal disease.

CONCLUSION

This clinical report describes a 31-year-old patient suffering from achondroplasia, showing manifestations of severe periodontal disease. Though no association between periodontal disease and achondroplasia has yet been established, this case can be a direction towards research in this area.