Molar–incisor malformation (MIM): a case report with a comprehensive review of the literature

3.1 Clinical characteristics of MIM

Molar–incisor malformation (MIM) represents a distinct developmental dental anomaly with characteristic morphological features that differ from conventional dental malformations. Clinically, affected first permanent molars typically exhibit normal crown contours, whereas radiographic examination reveals markedly short, thin, or underdeveloped roots. In the incisor region, characteristic findings include cervical enamel defects at the cervical third of the crown and pulpal calcifications or pulp stones. MIM most often presents bilaterally and predominantly involves the first permanent molars (maxillary and mandibular), second primary molars, and central incisors.

Epidemiological data from MIM cases reported between 2014 and 2019 indicate that 98.9% of patients exhibited involvement of the first permanent molars, 39.1% of the second primary molars, 35.6% of the central incisors, and 6.9% of the canines, with a mean patient age of approximately 9 years [1]. In a retrospective study of 38 patients [6], nearly all individuals demonstrated involvement of all four permanent first molars, with only three exceptions. Maxillary central incisors were affected in 17 patients (44.7%), mandibular central incisors in 2 patients, and maxillary canines in 4 patients (10.5%), including mandibular canine involvement in 2 cases (5.3%). Additionally, MIM-related changes were observed in the deciduous molars of 20 patients (52.6%). In the present case of the 9-year-old Chinese female patient, with four first molars involved, the characteristic features of MIM were clearly demonstrated, including cervical constriction of the maxillary central incisors and canines, extensive pulpal calcifications, and markedly underdeveloped roots of the first permanent molars, which were well documented by CBCT imaging.

3.2 Proposed etiology of MIM

The etiology of MIM appears to differ from that of previously described hereditary or environmentally induced dental anomalies. Current evidence suggests that MIM is not primarily driven by classical Mendelian inheritance, and several studies have proposed an association between MIM and systemic conditions affecting the brain and central nervous system during early childhood (approximately 1–2 years of age). In a case series of 12 affected children, 10 had documented medical histories of meningitis, spina bifida, epilepsy, hydrocephalus, or idiopathic encephalopathy occurring within this developmental window [5]. Similarly, an analysis of all reported MIM cases since 2019 identified prematurity (17.2%), meningitis (12.6%), early antibiotic exposure (9.2%), spina bifida (8.0%), stroke (6.9%), hydrocephalus (5.7%), and PHACE Syndrome (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac defects and coarctation of the aorta, and eye abnormalities) (4.6%) as the most frequently reported comorbidities. However, approximately 6.9% of patients had no significant medical history [1]. A recent five-case series further supported a non-genetic etiology of MIM, as affected children presented with heterogeneous systemic conditions—including pelvicaliectasis with nephrological follow-up, hemolytic uremic syndrome, severe neonatal hypertension requiring neonatal intensive care unit (NICU) admission, and multisystem disorders such as Williams syndrome—while no familial aggregation was identified [7]. Based on these observations, it is hypothesized—though not conclusively demonstrated—that vascular impairment or viral infection or systemic diseases during early development may interfere with root formation, leading to the characteristic dental phenotype.

In the present case, a detailed review of the patient’s medical history did not reveal any documented systemic diseases involving the brain or central nervous system during the critical period of 1–2 years after birth. Several prenatal and perinatal conditions were, however, identified, including maternal exposure to a freshly painted latex environment during early pregnancy, severe hyperemesis throughout gestation, and maternal calcium deficiency. In addition, the patient was diagnosed with a large hemangioma on the left leg at birth, which did not require surgical or pharmacological intervention. These factors are reported here as case-specific observations. Importantly, there is currently no direct evidence supporting a causal relationship between these prenatal or perinatal exposures and the development of MIM, and similar exposures are known to occur in many individuals who do not develop this condition [8].

To explore a potential genetic contribution to MIM in this patient, whole-exome sequencing was performed on peripheral blood as an exploratory analysis. Variant filtering was conducted using predefined criteria, including a minor allele frequency ≤0.05 across six population databases (Genome Aggregation Database (gnomAD) exome_ALL, gnomAD_exome_EAS, gnomAD_genome_ALL, gnomAD_genome_EAS, gnomAD3_genome_AF, and gnomAD3_genome_AF_EAS) or previously reported pathogenicity in ClinVar or the Human Gene Mutation Database (HGMD). Using these criteria, more than 10,000 candidate variants were initially identified (Supplementary Table 1). When the analysis was further restricted to genes associated with the phenotype of “central nervous system abnormalities”, three candidate genes—centrosomal protein 85 like (CEP85L), Abelson murine leukemia viral oncogene homolog 1 (ABL1), and DEP domain containing 5 (DEPDC5)—remained (Supplementary Table 2). However, due to the absence of family-based segregation analysis, as the parents were temporarily unwilling to undergo genetic testing, and the lack of functional validation experiments, the pathogenic relevance of these variants could not be determined. Therefore, no definitive causative mutation or genetic etiology could be established in this case. Further studies incorporating family-based sequencing and functional analyses will be required to clarify whether genetic factors contribute to the pathogenesis of MIM in a subset of patients.

Recent studies have also suggested a potential association between MIM and ciliary dysfunction resulting from mutations in the T-complex testis expressed 1 domain 2 (TCTEX1D2) gene during tooth development in a subset of patients [9]. Taken together, existing evidence indicates that MIM is likely a heterogeneous condition, potentially involving interactions between early-life systemic disturbances and genetic susceptibility. However, at present, these relationships remain largely associative, and the precise pathogenic mechanisms underlying MIM require further investigation.

3.3 Pathogenesis of MIM and pulpal calcifications

The formation of calcified masses within the pulp chambers of MIM-affected teeth has been attributed to early developmental disturbances during crown and root formation. It has been proposed that early injury to the vascular plexus at the base of the dental papilla disrupts normal tissue homeostasis, allowing serum or tissue fluid to infiltrate the follicular interstitial space and subsequently precipitate calcified spherules. These spherules may coalesce to form an ectopic mineralized structure known as the cervical mineralized diaphragm (CMD), which interferes with normal dentin mineralization and root morphogenesis by acting as a physical barrier at the crown–root junction [4]. Micro-computed tomography and histological studies of exfoliated MIM-affected molars have consistently demonstrated that the CMD exhibits a radiodensity intermediate between enamel and dentin and is primarily composed of hydroxyapatite-rich, amorphous hard tissue [10, 11]. Histological analyses further revealed that the pulpal floor of MIM-affected molars is composed of heterogeneous hard tissues, including dentin-, bone-, and cartilage-like components with abundant vascularization, suggesting inappropriate differentiation of apical pulp and dental follicle cells during tooth development [10, 11, 12]. At the dentin–pulp interface, irregular crystal-like deposits and reduced dentinal tubule density have been observed, supporting the notion that some of these calcified structures arise from passive mineral precipitation, rather than regulated cellular processes. Collectively, these findings indicate that CMD formation and associated pulpal calcifications create structural vulnerability at the crown–root junction, impair normal root morphogenesis, and increase susceptibility to pulpal and periapical pathology. In the present case, extensive pulpal calcifications were identified not only in the affected maxillary central incisor, but also in other teeth, supporting the hypothesis that aberrant cervical hard tissue formation may compromise pulpal integrity and predispose MIM-affected teeth—particularly tooth 21—to subsequent pulpal and periapical disease.

3.4 Differential diagnosis of MIM

In clinical practice, early recognition and diagnosis of MIM remain challenging, but are essential for appropriate management. Several pediatric dental conditions—including molar–incisor hypomineralization (MIH), amelogenesis imperfecta, and hereditary dentin dysplasia—may present with overlapping clinical or structural features, underscoring the need for careful differential diagnosis. MIH is a qualitative enamel defect of systemic origin, affecting at least one of the four first permanent molars and frequently involving the incisors. Clinically, it is characterized by demarcated enamel opacities larger than 1 mm in diameter, with altered translucency and color ranging from creamy white to yellow or brown. These lesions typically occur on the smooth buccal or lingual surfaces of first permanent molars and incisors [13, 14]. In contrast, MIM involves the same tooth groups, but is distinguished by normal coronal enamel mineralization. Affected incisors typically exhibit cervical constriction accompanied by intrapulpal calcifications, while the first permanent molars show markedly shortened, malformed, or absent roots. Despite superficial similarities in tooth distribution, these distinctive structural features—particularly the combination of normal enamel with severe root dysplasia in first molars—are critical for differentiating MIM from MIH.

Amelogenesis imperfecta (AI) is a group of hereditary enamel disorders and is typically classified into four major types: hypoplastic, hypocalcified, hypomaturation, and taurodontic forms [15]. Affected teeth typically exhibit generalized enamel defects, including surface pitting or depressions, with discoloration ranging from white to yellow-brown. The enamel may be of normal thickness or reduced and is often soft and hypersensitive. Both primary and permanent dentitions are usually involved, affecting multiple tooth types throughout the dentition [16]. Radiographically, the enamel in AI demonstrates radiopacity similar to or slightly lower than that of dentin. In contrast, MIM can be readily distinguished from AI by its localized pattern of involvement, preservation of coronal enamel mineralization, and characteristic radiographic findings, particularly the presence of cervical constriction and severe root malformations.

Dentin dysplasia (DD) is an autosomal dominant hereditary disorder of dentin formation and is clinically classified into type I and type II. Type I DD, also referred to as radicular dentin dysplasia, primarily affects root development, whereas type II DD, or coronal dentin dysplasia, predominantly involves the crowns [17]. Type I DD should be carefully differentiated from MIM. Clinically, affected teeth typically present with normal crown morphology and color, but exhibit increased mobility and a tendency toward premature exfoliation. Radiographically, type I DD is characterized by short, blunt, and malformed roots, with complete obliteration of the pulp chambers and crescent-shaped pulp remnants parallel to the dentino-enamel junction [18]. Although the short roots and obliterated pulp chambers observed in type I DD may resemble features of MIM, DD can be distinguished by its hereditary nature and its generalized involvement of the entire dentition, in contrast to the characteristic predilection of MIM for the first permanent molars and incisors.

In this case, normal enamel mineralization, characteristic cervical constriction, pulp calcifications, and severe root underdevelopment of the first permanent molars allowed differentiation of MIM from conditions such as MIH, AI, and DD.

3.5 Management considerations for affected teeth

Management strategies for MIM differ between affected incisors and first permanent molars. Maxillary central incisors with cervical constriction not only compromise esthetics, but also carry an increased risk of pulp infection and traumatic fracture with pulp exposure. Asymptomatic incisors may be preserved with appropriate coronal restorations, whereas teeth presenting with pulpitis or apical periodontitis may require endodontic treatment or, in severe cases, extraction [19]. In the present case, apical periodontitis of tooth 21 was likely associated with plaque accumulation and soft debris retention at the malformed cervical region, where abnormal structural interconnections with CMD dentin may facilitate bacterial ingress. The inflammatory process subsequently involved the pulp tissue and progressed to the periapical region. Given that maxillary central incisors usually have a single and relatively straight root canal, successful root canal therapy is often achievable. Considering the near-complete morphological closure of the apical foramen of tooth 21 and the relatively mild cervical enamel defect, nonsurgical root canal therapy was selected. Strict oral hygiene measures and regular follow-up were emphasized, and a definitive full-coverage restoration is recommended once craniofacial growth is complete. At the 9-month follow-up, tooth 21 remained asymptomatic with stable clinical and radiographic findings, indicating a favorable outcome. Consistent with this observation, among 17 reported MIM patients with incisor involvement, two experienced incisor loss, whereas four successfully retained their incisors following endodontic or restorative management [6].

For first permanent molars without clinical symptoms, an initial conservative approach with careful observation and periodic follow-up may be appropriate. In symptomatic cases, attempts at root canal therapy have been reported to preserve affected molars. A retrospective study of 38 MIM patients documented successful endodontic preservation of 10 first permanent molars [6]. In another case report, root canal treatment of bilateral mandibular first molars resulted in a favorable outcome on one side, while treatment failed on the contralateral molar due to severely calcified and non-negotiable canals [20]. Nevertheless, extraction has frequently been advocated for symptomatic MIM-affected first permanent molars when performed at approximately 8–9 years of age, to facilitate spontaneous mesial migration of the second permanent molar, particularly in patients with developing third molars [21, 22, 23]. This preference largely reflects the challenges posed by abnormal root morphology and complex canal configurations, which substantially reduce the predictability and success of endodontic treatment.

In the present case, management was individualized based on clinical findings. Root canal therapy was performed for the symptomatic maxillary central incisor with a nearly closed apex, while asymptomatic first permanent molars were managed conservatively to maintain occlusal stability and masticatory function. Extraction of first permanent molars may be considered if symptoms develop or if eruption of the second molars is compromised.

This case report has several strengths. To our knowledge, this is the first reported case of molar–incisor malformation in a Chinese pediatric patient. In addition, genetic testing was performed to explore potential pathogenic variants, providing preliminary molecular insights into this rare condition. Comprehensive clinical management was implemented, including microscopic endodontic treatment, CBCT-based assessment, oral hygiene intervention, and long-term monitoring of both affected and at-risk teeth, emphasizing a whole-dentition management approach. Nevertheless, several limitations should be acknowledged. The follow-up period was limited to nine months, and longer observation is necessary to evaluate long-term outcomes, particularly for the first permanent molars. Moreover, family-based genetic analysis could not be completed because the patient’s parents declined further genetic testing, limiting definitive conclusions regarding the genetic etiology of MIM in this case.

Building on these considerations, this case provides several clinically relevant lessons. First, MIM should be considered in young patients presenting with cervical constriction of incisors and unexplained pulpal or periapical pathology, even in the absence of obvious enamel hypomineralization. Second, poor oral hygiene may exacerbate the vulnerability of malformed cervical structures, facilitating microbial ingress and subsequent pulpal involvement. Third, affected incisors with relatively simple canal anatomy and near apical closure may be successfully managed with conventional root canal therapy. Finally, asymptomatic first permanent molars may be managed conservatively with regular monitoring, while extraction should be reserved for cases with severe symptoms or unfavorable root morphology. Collectively, this case underscores the importance of early recognition, individualized treatment planning, and long-term surveillance in the management of MIM.