Overview

Frontofacionasal dysplasia is a rare genetic disorder with abnormal bone development, marked by malfunctioned eyes, forehead, and broad nose before birth, often linked to disabled handwriting.¹ The disorder is mainly marked by abnormalities in the head and facial region, along with eye defects. Craniofacial malformations may include a short, broad head, an incomplete closure of the roof of the mouth, an abnormal indentation in the upper lip, and an underdeveloped nose with malformed nostrils. Frontofacionasal dysplasia is thought to follow an autosomal recessive inheritance pattern.²

Types

There are three types of Frontofacionasal dysplasia, and each type is linked to distinct features.³

• Type 1 in which the individuals often display nasal abnormalities, an elongated upper lip and nose, and drooping upper eyelids
• Type 2 individuals may experience hair loss and an expansion of the openings in the parietal bones that form the upper and lateral parts of the skull. Males with this type of condition frequently exhibit genital abnormalities
• Type 3 is characterized by absent or underdeveloped eyes, along with low-set backward-rotated ears. This condition is usually linked to the most pronounced facial abnormalities, though the severity can differ significantly, even among individuals with the same type

Etiology

• Frontonasal dysplasia type 1 results from mutations in the ALX3 gene
• Type 2 is associated with mutations in the ALX4 gene 
• Type 3 is linked to mutations in the ALX1 gene
• Both types 1 and 3 are inherited in an autosomal recessive pattern, while type 2 follows an autosomal dominant inheritance pattern³

Signs and clinical symptoms

It may exhibit the following clinical signs and symptoms by the individual affected by the disease condition.^4-9

• Distinct abnormalities of the skull bones along with facial, nasal, and eye defects. These may include the premature fusion of the fibrous joints between certain skull bones, resulting in an unusually short and broad head
• Early bone formation in the base of the skull is also common, and the air-filled cavities around the nose may be abnormally enlarged
• Underdevelopment of the midface often occurs
• Underdeveloped frontal bone and a congenital opening in the skull. In some cases, this may lead to the protrusion of brain tissue and membranes through the skull defect, while in others, no brain abnormalities are present
• Distinctive nasal abnormalities are another hallmark of frontofacionasal dysplasia, including underdeveloped nasal structures and malformed nostrils, such as the underdevelopment of the nasal wings
• Affected infants may also have cleft palate and cleft lip, which can cause feeding difficulties and lead to dental abnormalities like misaligned, malformed, or missing teeth. These malformations may also contribute to speech issues and an increased risk of middle ear infections
• A bifid uvula, or split uvula, may also be present
• Ocular abnormalities are commonly seen, including wide-set eyes, increased distance between the inner eyelid corners, and narrow, "S-shaped" eyelid folds
• Other physical abnormalities also be present, such as noncancerous fatty tumours in the forehead or a widow’s peak, a "V-shaped" hairline extending onto the forehead

Diagnosis

This is normally carried out after birth based on clinical evaluation, identification of physical characteristics and special tests. However, in some cases, a diagnosis of frontofacionasal dysplasia may be suspected prenatally based on the identification of specific physical abnormalities during a fetal ultrasound such as facial clefts and encephalocele 10. The following can help in the diagnosis of frontofacionasal dysplasia.

• Computerized Tomography (CT) scanning  
• Magnetic Resonance Imaging (MRI)
• Ultrasound

Anatomical considerations in frontofacionasal dysplasia

The following are considered in the frontofacionasal dysplasia:

• Craniofacial abnormalities such as clefting, midfacial hypoplasia, hypertelorism, and deviations in nasal and oral structures affect airway passage^11-13
• Effects on airway structure which include nasal obstructions because of septal abnormalities, maxillary and mandibular misalignment and their effect on oral airway space. Additionally, there can be a potential pharyngeal collapse from abnormal facial bones

Drawback in airway management

There are many challenges in airway management because of the disease condition. These challenges involve the following;

• Airway obstruction: This can be a complete or partial obstruction in nasal or oral passages and difficulty in establishing a clear airway during surgical procedures
• Intubation issues: This occurs when there is limited access to the oral and nasal cavity because of deformities. Furthermore, problems with laryngoscope insertion due to altered anatomy
• Mask ventilation problem: Inefficient ventilation because of craniofacial abnormalities and poor mask fit over irregular facial structures contributes significantly to drawbacks in airway management
• Tracheostomy considerations: There are difficulties in performing tracheostomy in dysplasia patients and potential complications because of abnormal tracheal positioning

Preoperative assessment and planning

• Detailed airway evaluation: This involves the use of imaging techniques such as CT, and MRI to assess anatomical variations of the disease condition. Additionally, a physical examination should be carried out to assess the airway patency and obstruction
• Collaborative approach: This entails team spirit involving multidisciplinary health professionals like anesthesiologists, craniofacial surgeons, and ENT specialists to get a holistic approach to the best treatment for the patient. In addition, this helps in customizing airway management strategies which aids in tailoring plans based on the severity of craniofacial deformities and

Treatment approaches for airway management of frontofacionasal dysplasia

Treatment is based on patient-specific needs as clinical presentations differ for each patient.² This might require teamwork from health professionals to be able to achieve the desired outcomes. The following methods can be adopted for treatment;

• Non-invasive methods: Use of supraglottic airway devices, CPAP or BiPAP for airway support in non-emergency cases
• Advanced intubation methods: Use of fiberoptic bronchoscopy for difficult intubations and video laryngoscopes for better visualization
• Surgical approach: Intervention through surgical procedures like tracheostomy and corrective craniofacial surgeries to improve airway management and patency

Postoperative airway management

• Close monitoring for airway obstruction due to the risk of swelling or collapse.
• Long-term airway care: This involves a follow-up care plan for patients with permanent airway modifications and managing potential respiratory complications associated with craniofacial growth.

Summary

There is a need for early and individualized airway planning to aid in therapy approaches to optimize the desired therapeutic outcomes and reduce costs and risks associated with the disease condition.