Introduction

Frontofacionasal dysplasia (FFND), also called frontonasal dysplasia (FND), is a rare genetic disorder that is apparent at birth (congenital). It develops due to abnormal formation of the facial midline.¹ In fact, the term frontonasal dysplasia (FND) has been used to characterise a pattern of anomalies of the facial midline defect.² 

Craniofacial anomalies in FND include a gap at the front region in the skull bone, wider eye sockets than normal, malformation of lips and the mouth-roof, and a split in the nose-wings.¹ 

The disorder is primarily characterised by malformations of the head, face, front of the skull area, and eye defects.

General characteristics and symptoms of FND

Clinically, FND has been defined to represent two or more of the following signs:

• Wider eye sockets (eye hypertelorism)
• Broadening of the base of the nose
• Median facial cleft impacting the nose, upper lip, and palate
• Cut in the one or both nose-wings
• Absence of the nasal tip
• Gap in the skull at the front side
• A V-shaped or widow's peak frontal hairline.^{1, 3}

Craniofacial malformations may also include an unusually short, broad head (brachycephaly); incomplete closure of the roof of the mouth (cleft palate); an abnormal groove in the upper lip (cleft lip); and underdevelopment (hypoplasia) of the nose with malformation of the nostrils.⁴ 

Developmental mechanisms responsible for FND remain unclear, but dysregulation of the fusion process of the front part of the face during the embryonic phase must be considered a prominent feature of the disease.⁵

It is worth noting that this disorder can be present independently or in association with other diseases.

Importance of understanding dental abnormalities in FND

The prevalence of this disorder is associated with identifying isolated clinical signs like cuts in the midline of the face, found in 1 in every 100,000 births.³ 

Causes of dental abnormalities in FND

Genetic basis of FFND

Inheritance patterns and associated gene mutations

The occurrence of FND is exclusively irregular; nearly all cases occur sporadically without basic genetic evidence.^{2, 6}

This dysmorphic syndrome is polygenetic because it can be inherited through both dominant and recessive traits. The parents of affected children can expect a 25% risk of the next child developing this disorder.⁶    

Role of genetic factors in skull and facial development

There is little or no evidence regarding the exact cause of the development of FND; however, some studies reported investigating patients with holoprosencephaly (a condition in which both halves of the brain are not completely separated) and showed a 485C→T mutation in exon 4 of the TGIF gene. Thereafter, the mutation in this gene has been suggested as one of the causes of FND development.⁷

The anomalies noted in the current condition are related to embryology, occurring during the same critical period, likely in the early stages of forebrain induction. This results in anomalies involving the frontonasal process, midfacial structures, and the primordium of the eyes.

Developmental pathways affected in FND

Impact on craniofacial and dental structures

The most prevalent craniofacial defects impact the growth and development of the first arch structures, including the prominence and formation of the oral cavity.⁸ 

There are 3 types of FND, with type 3 being the most severe form. In FND Type 3, there is a complete failure of fusion between the frontonasal and maxillary arch-derived tissues, thus, the patient suffers from midfacial clefting.⁹

Common dental issues in FFND patients

Tooth agenesis (Missing teeth)

Tooth agenesis occurs when there is a developmental absence of one or more of the normal complement of 20 teeth in the primary dentition and/or 32 teeth in the permanent dentition.¹⁰ 

Tooth agenesis leads to increased dental alterations. Some studies have suggested that tooth agenesis predominantly impacts the lateral incisors and second premolars.² 

Various clefts such as median upper lip notch, median cleft lip, unilateral cleft lip, unilateral cleft lip and palate, bilateral cleft lip and palate, and cleft palate and bifid uvula occur in isolated cases of the FND.³

The most common occurrence in children with cleft lip and palate CLP is the congenital absence of the permanent lateral incisor on the cleft side.¹¹

Associated challenges

Children born with cleft lip may have difficulties in feeding; suckling is slow due to inadequate intraoral pressure generated while milk is being lost through the nose/cleft before it’s swallowed.¹¹

Other Issues could arise with the speech of the child, especially in cases of oral cleft, because of inadequate functioning of the soft palate, causing velopharyngeal insufficiency.¹¹

Malocclusion (Misalignment of teeth)

The most reported dental anomaly in FND patients has been malocclusion and dental crowding 

(mostly anterior region) which is secondary to the alveolar bone expanding at a rapid rate, causing improper positioning of the dentition.¹² 

The Anterior open bite is observed in individuals with median cleft, likely occurring because this type of cleft alters the anatomy of the anterior oral region. These modifications can be accompanied by malocclusions.

Individuals with median clefts exhibited anterior open bite, although only individuals with oral clefts presented tooth agenesis and bilateral posterior crossbite.² 

The presence of posterior crossbite is characterised by posterior abnormal development of the jaws, facial imbalance appearance and a high palate.¹³  

Implications for function and orthodontic treatment

Orthodontic treatment aims to open natural passages, which are closed in FND and gain space in the maxilla and mandible for the eruption of the permanent mandibular premolar.³ The treatment process lasts longer 

Supernumerary teeth (Extra teeth)

Not all cases of FFND or FND occur with supernumerary teeth. As previously mentioned, most symptoms are isolated to different individuals.

The presence of extra teeth in this condition can cause overcrowding. The teeth that appear out of correct alignment and levelling compromise the aesthetics and hygiene of the oral cavity, resulting in gum disease development.³

Abnormal tooth morphology

Abnormalities in tooth size and shape are said to result from disturbances in tooth morphodifferentiation.¹⁴

Teeth resulting from fusion can be present. In most cases, fusion occurs between the central and lateral incisor, with the lateral incisor often thought to be missing. However, this is a very rare and isolated dental anomaly affecting people with FND.

Delayed tooth eruption

Delayed eruptions have been known to take place in the upper jaw of patients with orofacial related to the mouth and face clefts.¹⁴ These patients experience late growth of their permanent upper lateral incisor and second permanent molar. This experienced delay is likely to be caused by the affected bones and teeth.¹⁴

Impact on oral health and development

Delayed tooth eruption may be caused by dental crowding, which occurs when there is a mismatch between tooth size and arch dimension, leading to malocclusion.¹⁵

It is a sign of a lack of space in the arches due to reduced size (Micronathia), and is not self-correcting and can be severe with time.¹⁵ 

Diagnostic approaches to dental abnormalities in FND

Clinical examination

Clinical examination is performed by a geneticist at birth of the child. A dental examination is performed by a trained dentist to diagnose misalignment, hard palate, occlusion, missing teeth, etc.

Radiographic imaging

Prenatally, craniofacial deformities can be observed by 3D ultrasound, which has been shown to improve the successful diagnosis of FND. 3D ultrasound is used to provide clinical geneticists with a potential facial appearance that is likely to aid in the diagnosis of FND.¹⁶

Radiographs are thus valuable tools, in addition to clinical examinations, to be used for dental disease diagnosis. In dentistry, different radiological techniques are used to identify dental abnormalities, including those associated with FFND. 

Panoramic imaging assesses bone support, dentition, etc. It helps to identify supernumerary teeth and toothagenesis, etc.¹⁷

Cephalometric radiographs analyse the relationships between cranial and dental structures, including growth and development. This can be used in cases of orthodontic treatment.¹⁷

Various imaging techniques are used for treatment planning that monitor the progression of the surgical treatments. It also provides a guide and any modification to the developing structures involved in the syndrome.¹⁸

Genetic testing

FND diagnosis is performed by a clinical geneticist through examination at birth based on facial abnormalities.³ Most dental abnormalities can be identified after the first year of life.

Early genetic testing, leading to a molecular genetic diagnosis, can be crucial to establishing optimal therapeutic strategy, with the ultimate goal of improving the quality of life for these patients.¹⁹

Management of dental issues in FND

Multidisciplinary care approach

Since various body structures are affected in this syndrome, there is a need for a multi-disciplinary team such as neurologists, paediatricians, geneticists, ophthalmologists, otolaryngologists, and orthodontist surgeons to manage patients.³ With the collaboration of different practitioners, there is shared responsibility and accountability in achieving the desired goals.

Those affected by this disorder should undergo long-term follow-up to monitor for lesion growth and progression. Periodic Maxillofacial CT scans are recommended during a patient's growth phase, and long-term follow-up is essential to monitor any changes in lesion size and progression.¹²

Orthodontic interventions

The orthopedic goals for managing lesions are to optimise and reduce the morbidity of the deformity. In the pediatric population, conservative techniques are recommended.¹² 

Orthognathic surgery (jaw repositioning surgery), in combination with orthodontic therapy, thus significantly reduces issues with malocclusion.¹²

The orthodontic treatment aims to correct skeletal atresia while gaining space in the (upper jaw) maxilla and (lower jaw) mandible for the smooth eruption of the permanent mandibular left second premolar.³ This treatment is usually recommended early, such as leverage made on the growing structures of the jaws.

Orthodontic treatment improves the hard palate, malocclusion, and overcrowding. This emphasises the importance of maintaining good oral hygiene and regular dental check-ups to monitor treatment progress.

Surgical options

Treatment of this disorder varies with the severity of the physical characteristics. Children affected with oral clefts are advised to have surgery, which stops the communication between structures.

Impact of dental abnormalities in FND

The treatment is to improve function and aesthetics of the patient based primarily on the age. It also aims to improve facial appearance while reducing shyness and shame.³

The psychological trauma experienced when a patient becomes aware of the deformity and the subsequent impact on self-esteem will necessitate Surgery to correct the craniofacial abnormalities associated with the disorder.²⁰ 

Those affected by this disorder should be provided with genetic counselling to provide a better understanding of the disorder and its management.

Summary

Frontonasal dysplasia (FND) is a rare sporadic congenital deformity. In FND, many abnormalities are observed, like clefts in the lips and nostrils, underdevelopment of the skull, and palate malformation.

Dental conditions are of major concern associated with FND and caused by changes that occur at the genetic level, also called mutations. These further lead to other challenges, like in the newborn, where suckling becomes difficult as the cleft does not allow the generation of the required amount of pressure in the mouth. Besides, confidence gets hampered many times due to the abnormal appearance.

From counseling to a high-level surgery option might be considered, or a multidisciplinary approach may be required, depending on the severity of the condition.