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.