Syndromic and Non-syndromic CL/P

There are two clinical types of CLP - Nonsyndromic and Syndromic. Nonsyndromic forms refer to cases where there are no other evident anomalies or features, accounting for around 50% of CP cases and 70% of CL and CLP cases. On the other hand, syndromic forms have additional manifestations, and their causative genes have been characterized. ^[1,5]

Of these syndromes, velocardiofacial syndrome is the most common microdeletion syndrome, affecting the 22q11 region. It commonly includes abnormalities of the palate (60–80% usually manifested as a cleft of the soft palate, submucous CP, or bifid uvula), heart, and recognizable facial features.^[1] Other clefting syndromes for which the genetic basis has been identified include Loeys-Dietz syndrome (by imbalanced TGF); Shprintzen-Goldberg syndrome (by mutations in a suppressor of TGF signaling); and frontonasal dysplasia-3 which is caused by homozygous mutation in the ALX1 gene on chromosome 12q21.^[1]

Fig 11: Frontonasal dysplasia type 3. The patient presented with anophthalmia-microphthalmia, coloboma, CLP, ventricular septal defect, and mild turricephaly. A and B) Facial CT done two years before facial CT C and D). Bilateral complete CLP consisting of two bony defects in the alveolar process of the maxilla (on the right between teeth 11 and 12, and the left between teeth 22 and 23) converging at the midline, resulting in a broad bony defect affecting the entire hard palate. There is also a partial absence of ossification in the superomedial wall of the right orbit.

CP is also a frequent feature of several craniosynostosis syndromes, such as Apert, Crouzon, and Saethre-Chotzen syndromes, as well as disorders affecting collagen synthesis, like Stickler syndrome, which includes ocular, auditory, and skeletal manifestations and is the most commonly associated syndrome in patients with isolated CP. ^[1,5]

Imaging diagnosis

While diagnosing CLP is not usually missed clinically, being able to interpret its appearance through imaging has its advantages. Firstly, with fetal ultrasonography and magnetic resonance imaging, the diagnosis can be made in utero, which can affect care throughout the pregnancy, postnatal period, and the child's life. Secondly, patients with CLP may have associated anomalies in the intracranial and extracranial regions and dentofacial deformities.^[4,8]

Imaging of CLP continues throughout the patient's life. As a child with CLP grows, imaging is needed to determine treatment options, timing of surgical repairs, and post-treatment effectiveness. Although there are different imaging modalities to assess associated anomalies and treatment outcomes in the postnatal period, CT is preferred.^[4,9,10]

Fig 12: Facial CT. A) Volumen rendering and B) Expanded and oblique coronal reconstruction. Left CLP with a bony gap of approximately 4.5 mm (arrow).

Cleft lip and palate classifications

There are different classification systems for craniofacial clefts. The Nyberg classification system is based on antenatal ultrasound imaging and is divided into five types, which correlate well with the severity of the defect and outcomes. Type I indicates an isolated cleft lip; Type II indicates a unilateral cleft lip and palate; Type III indicates a bilateral cleft lip and palate; Type IV indicates a midline/median cleft lip and palate; and Type V indicates facial clefts. However, an isolated cleft palate is challenging to diagnose in utero and is not part of this classification.^[3,11] Another widely used classification system is the Tessier classification, which groups craniofacial clefts based on their location. According to Tessier's classification, there are four groups, and the first and second groups are related to oral clefts: ^[12,13]

Fig 13: Schematic drawings of different facial clefts. Based on Tessier P. Anatomical classification of facial, cranio-facial and latero-facial clefts. J Maxillofac Surg. 1976;4:69–92. http://dx.doi.org/10.1016/s0301-0503(76)80013-6

• Oral-nasal clefts are Tessier Clefts 0-2: involve the midline structures such as the lips and nose. 
• Oral-ocular clefts are Tessier Clefts 3-5 and occur between oral and orbital cavities. Tessier cleft 4 and 5 without disrupting the nose.
• Lateral facial clefts are Tessier Clefts 6-8, resulting in conditions such as Treacher Collins Syndrome, hemifacial microsomal, and necrotic facial dysplasia.
• Cranial clefts are Tessier clefts 9-14 and occur in the frontal and cranial vault.

Fig 14: A) Schematic drawing of Tessier 0. B) Volumen rendering, C) coronal reconstruction, and D) sagittal reconstruction facial CT of Tessier 0.

Fig 15: A) Schematic drawing of Tessier 1. B) expanded and oblique coronal reconstruction, C) and D) volume rendering facial CT of Tessier 1.

Fig 16: A) Schematic drawing of Tessier 2. B) volume rendering, C) expanded and oblique coronal reconstruction facial CT of Tessier 2.

Fig 17: A) Schematic drawing of Tessier 3. B) expanded and oblique coronal reconstruction, C) and D) volume rendering facial CT of Tessier 3.

Imaging throughout childhood and complications

Even when there are no associated anomalies, imaging throughout childhood remains important in identifying dentofacial deformities due to cleft lip and palate, which may include missing or supernumerary teeth, oronasal fistulas, velopharyngeal insufficiency, hearing loss, maxillary growth restriction, and airway abnormalities.^[4]

Dentition: Patients who have CLP may exhibit missing or supernumerary teeth, which can cause abnormal eruption patterns, resulting in poor periodontal support and a compromised prognosis. The dental abnormalities can lead to malocclusion, often including an anterior crossbite and/or open bite. A combination of orthodontic treatment and orthognathic surgery can be used to correct this type of malocclusion.^[4,5]

Fig 18: Facial CT. A) expanded and oblique coronal reconstruction, B, C, and D) different volume rendering. Bilateral complete CLP which is affecting the alveolar process of the right maxilla between 11 and the temporary canine and the left maxilla between 22 and the temporary canine. The fissures extend to the hard palate and converge in the midline with a bony defect affecting the entire hard palate, leaving a central isolated bony portion anterior in the upper maxilla, dependent on the vomer with dental pieces. A tooth with an inverted vertical orientation is observed on the floor of the right nasal fossa. Presence of a palate expander.

Oronasal Fistulas: Persistent or recurrent oronasal fistulas may become apparent after palate repair. Fistulas of the palate or alveolus can be noticed by the patient, but a radiologist may detect a hard-tissue defect in the palate covered or not by mucosa. These defects can be easily seen on coronal or sagittal CT.^[2,4,5]

Fig 19: A) Facial CT in 2021 after cleft palate surgery (square). B) and C) Facial CT in 2021. Good coverage of the right alveolar defect with a failure to cover the left (arrows). Anterior left oronasal fistula.

Fig 20: Facial CT for control of surgical bone graft in the anterior region of the orbital floor. A) and B) coronal reconstruction and C) volume reconstruction showing partial resorption with incomplete bone coverage. The resorption has mainly occurred in areas in contact with the fixation material. The graft remains positioned below the floor of the left orbit, causing a descent of the eyeball. Additionally, the bone defect persists in the inferior and medial walls of the orbit. There is no evidence of entrapment of the inferior rectus muscle or orbital fat.

Fig 21: Facial CT two years after Fig 20. A) Volumen rendering, B) MIP bone reconstruction, and C) sagittal reconstruction. Sequels of maxillary bone graft and metallic fixation plate in the maxillary bone at the level of the inferior orbital rim and anterior third of the floor of the right orbit. Currently, the floor of both orbits is at a similar height, with symmetrical eyeballs, and preserved size and morphology.

Velopharyngeal Insufficiency: Velopharyngeal insufficiency is a condition where the nasopharynx cannot be closed off by the soft palate during speech, which can cause speech alterations. Radiological imaging can be used to measure the ratio of soft palate length and airway depth at the level of the hard palate to predict the risk of velopharyngeal insufficiency before maxillary advancement. ^[1,4,5,14]

Hearing Loss: The tensor muscles may not work, leading to a buildup of fluid in the middle ear through the Eustachian tubes and hearing loss. If there is a presence of middle ear infections or effusions, or if the person has had tympanostomy tubes inserted, it should be noted in the radiology report.^[4,5]

Maxillary Growth Restriction: The scarring from palatal surgeries causes maxillary growth restriction which cannot be fully assessed until the permanent teeth have erupted (be measured in the anteroposterior, vertical, and transverse dimensions). As part of the therapy for maxillary constriction, the maxillary expansion process may involve orthodontics, such as a quad-helix expander in a slow maxillary expansion, or a Haas or Hyrax expander in a rapid maxillary expansion. ^[4,15]

Fig 22: A) Orthopantomography. B) Hyrax expander volume reconstruction. C) Maxillary bone reconstruction of cleft palate.