Discussion
A potential biological foundation for the emergence of short roots can be elucidated through an examination of the regulatory function of the Nfic gene (Park, 2007; Yu, 2019). The aberrant expression of specific factors, including Nfic, Osx, Hh, BMP, TGF-β, Smad, Wnt, β-catenin, DKK1, and other recently identified proteins, can contribute to the development of SRA. The absence of the Nfic gene, which is critical for odontoblast differentiation, has been demonstrated to result in the development of short, abnormal roots in rats through immunohistochemical and in situ hybridization studies. It has also been proposed that Nfic knockout mice display abnormalities in bone formation and maintenance, which may indicate a more extensive involvement in skeletal development (Lee et al., 2013). The precise regulation of Wnt/β-catenin signaling is of great importance during root morphogenesis. Further research is required to elucidate the specific mechanisms underlying these effects (Yu, 2019). Given that hemimelia is characterized by skeletal abnormalities, it is plausible that mutations or deletions in genes such as Nfic may contribute to the development of limb deficiencies.
Bone morphogenetic proteins (BMPs) constitute a group of growth factors that are critically important in the regulation of bone and cartilage development. They are members of the transforming growth factor-beta (TGF-β) superfamily and play crucial roles in several developmental processes, including the formation of teeth and limbs. BMPs, which interact with the Nfic gene in dental development, are also essential for limb development (Chen et al., 2012). The involvement of BMPs in both SRA and hemimelia suggests the existence of a potential link through common developmental pathways. Mutations in genes that regulate BMP signaling are critical for the proper development of dental roots (Li et al., 2017).
It is well documented that prenatal exposure to specific drugs is a prevalent risk factor for the development of both SRA and hemimelia. Thalidomide, a known teratogen, has been identified as a potential cause of limb defects such as hemimelia and dental anomalies including SRA (Bermejo-Sánchez et al., 2011; Puranik et al., 2015. Metabolic disorders such as hypophosphatasia, which affects bone mineralization, can also impact dental root development, leading to SRA (Wei et al., 2010). A deficiency of vitamin D and associated conditions such as vitamin D-dependent rickets type I have been linked to SRA due to their role in bone and dental development (Zambrano et al., 2003). Pregnancy-related deficiencies in essential vitamins and minerals, particularly in the context of poor maternal nutrition, can contribute to the development of congenital limb deficiencies (Bermejo-Sánchez et al., 2011). Retinoic acid (RA), a metabolite of vitamin A, plays a critical role in embryonic development. RA levels must be meticulously regulated during limb bud development, as both elevated and diminished levels are linked to developmental abnormalities (Bermejo-Sánchez et al., 2011). Pregnant women with high or low levels of RA have been found to have an increased risk of developing developmental abnormalities. RA regulates the Hox genes involved in limb and dental development, influencing the formation and differentiation of chondroblasts and osteoblasts, as well as regulating chondrocyte maturation and bone formation (Bermejo-Sánchez et al., 2011). It can thus be surmised that irregularities in RA levels may be a contributory factor in the development of both SRA and hemimelia.
Despite the presence of SRA throughout the dentition, the third molars were fully formed, exhibiting no indications of the corresponding appearance of rounded apices, which would be expected given their young age. The formation of the roots of permanent teeth is typically completed four to five years before the formation of the third molars (Wilson et al., 2021). It is not possible to determine whether SRA is present in third molars based on the root/crown ratio alone, as these teeth vary significantly in size and shape. It is plausible that the factor influencing the root length of all other teeth did not affect the third molars.
Hypodontia and taurodontism are common accompanying clinical findings in cases of SRA (Puranik et al., 2015). Hypodontia is a dental anomaly, with a frequency of 6.9% across the general population, with the most affected teeth being the premolars, accounting for up to 2.2% of cases (Polder et al., 2004). Taurodontism is a condition where the ratio of the pulp chamber length to the total length of the pulp is reduced, resulting in teeth having a characteristic appearance. An enlarged pulp chamber, an apical position of the pulpal floor, and a lack of constriction at the level of the cementoenamel junction are the main features, affecting molar teeth and resulting in the roots being closer together or even fused (Shifman and Chanannel, 1978).
SRA primarily raises concerns pertaining to aesthetics and restoration. However, with meticulous treatment, the prognosis of the dentition is typically favorable in cases of isolated dental groups. The occurrence of generalized SRA is considered rare (Apajalahti et al., 2002). The potential for possible deterioration of the clinical condition concerning tooth support has not yet been studied longitudinally in cases of SRA. Patients with SRA are at risk of developing periodontitis or increased tooth mobility due to poor root support. Under protective measures, the clinical picture of SRA remains stable (Valdares-Neto et al., 2013; Trimeridou et al., 2023). SRA presents a significant therapeutic challenge across all areas of dentistry, particularly in endodontic, periodontal, orthodontic, and prosthetic restoration.
Congenital limb malformations have substantial social and psychological implications for both the patient and the family environment. This was evident throughout the history-taking process, particularly with regard to the pregnancy period, during which the parents were reluctant to provide detailed information about ultrasound examinations and prenatal screening and expressed negativity towards supplementary examinations such as CBCT or intraoral radiographs. Additionally, the parents were opposed to taking any photographs, either intraoral or of the missing limb.
As this is the first documented case presenting with these concurrent conditions, further research is necessary to determine any potential direct associations or shared underlying pathophysiological mechanisms between them.