Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Craniofacial abnormalities


Craniofacial Clefts

Craniofacial clefts (CFC) are rare congenital malformations. They may involve the whole head or be limited to subtle defects in apposition of junctional facial structures. These complex malformations may be isolated or syndromic; they have significant functional, psychological and esthetic implications.

The origin of clefting is not well understood. Failure of neural crest cell migration or degeneration of these cells prior to migration, resulting in structural collapse and epithelial dehiscence, has been proposed. Maternal cocaine use, anti-epileptic and benzodiazepine use are occasionally implicated. Apart from Treacher Collins syndrome, heredity seems to play only a minor role.

Numerous attempts have been made to classify the broad spectrum of craniofacial anomalies, and these highlight the variable features and severity with which these anomalies may present. Tessier’s classification, an architectural description of defects, is most widely accepted, dividing the face vertically through the midline ( Fig. 26.1 ). Common to the cranium and face, the orbit is regarded as the reference landmark. Tessier numbered CFCs from 0 to 14 according to the constant axes through the orbit. Severe clefts may include combinations as well as the globe. Each cleft has variable involvement of soft tissue and underlying bony skeleton. Generally, medial clefts have more soft tissue involvement than bony abnormality and lateral clefts more bone than overlying soft tissue deformity.

Fig. 26.1, Tessier classification of craniofacial clefts. An architectural description. (A) Soft tissue; (B) skeletal.

Several clefting syndromes are of significance to the ophthalmologist. To simplify the ophthalmic manifestations of clefting syndromes, Fries and Katowitz 1990 conveniently grouped orbital clefts into four regional categories progressing from medial to lateral.

R

egional classifications

Area 1: Median facial cleft syndrome ( Fig. 26.2 )

Tessier clefts 0, 1, 13, 14, where the major clinical sign is hypertelorism. Less commonly frontoethmoidal meningoencephalocele may occur ( Fig. 26.3 ), or giant pneumatisation of the frontal sinus.

Fig. 26.2, Median facial cleft syndrome. (A) A male newborn with Tessier type 0 cleft showing depression of nose, cleft palate, and telecanthus. (B) CT reconstruction demonstrating underlying orbital hypertelorism. (C) Cleft marked in red.

Fig. 26.3, (A) This young boy has a large frontoethmoidal meningoencephalocele causing an exotropia and elongation of the face. (B) This CT reconstruction demonstrates the bony cranial deficit.

Area 2: Medial canthal/nasolacrimal clefts ( Fig. 26.4 )

Tessier clefts 2, 3, 4 (rarely superior counterparts 10, 11, 12). Manifesting clinically as canthal dystopia and nasolacrimal disorders with varying degrees of hypertelorism and telecanthus depending on bone or soft tissue involvement. The nasolacrimal system is quite disturbed, and rarely permits easy reconstruction.

Fig. 26.4, Medial canthal/nasolacrimal cleft syndrome. (A) This boy has a right Tessier type 3 cleft with vertical soft tissue deficiency from cleft lip/palate extending toward the medial canthus with canthal dystopia and distortion of the nasal ala and side wall. He also has a superior type 10 soft tissue cleft with upper lid coloboma and brow distortion. (B) CT reconstruction shows right cleft through palate, inferonasal orbital rim, and ethmoids with right orbital dystopia. (C) The Tessier 3 cleft is shown in red.

Area 3: Eyelid clefts ( Fig. 26.5 )

Tessier clefts 4, 5, 6, superior counterpart 9, 10, 11. Eyelid coloboma is the main clinical sign; less commonly cryptophthalmia, microphthalmos and anophthalmos may be occur. Orbital contents may prolapse into the maxillary sinus. Even when the globe is normal, it may be threatened by exposure secondary to the lid deformity.

Fig. 26.5, Eyelid cleft syndrome. A boy with bilateral Tessier type 4 clefts with soft tissue deficiency extending from a cleft lip to the medial lower eyelid. There is also canthal dystopia and right orbital dystopia. CT reconstruction shows bilateral maxillary clefts of the inferior orbital rim with associated right orbital dystopia. The Tessier 4 clefts are shown in red.

Area 4: Lateral canthal clefts ( Fig. 26.6 )

Tessier clefts 6, 7, 8. The primary clinical sign is lateral canthal dystopia and severe forms can present with ear deformities, auricular tags, mandibular and maxillary hypoplasia, and parotid/tongue/hard-palate hypoplasia. The trigeminal and facial nerves may be affected. These clefts are rarely isolated but more commonly associated with craniofacial microsomia and Treacher Collins syndrome.

Fig. 26.6, Lateral canthal cleft syndrome. (A) A boy with bilateral Tessier type 6 clefts has a severe vertical soft tissue cleft from the oral commissure on the right and a furrow on the left to laterally placed lower eyelid clefts. Lateral canthal dystopia leads to anti-mongoloid deformity of the lateral canthus, ectropion, and orbital dystopia. (B) CT reconstruction demonstrating cleft of right zygomaxillary suture with hypoplastic maxilla and orbital rim. (C) Tessier 6 clefts are shown in red.

Craniofacial microsomia

Craniofacial microsomia (CFM) encompasses a broad phenotypic spectrum of malformations involving structures derived from the first and second branchial arches with variable penetrance and etiologic heterogeneity. The incidence of this disorder is at least 1 in 5600 live births. CFM is known by several names, which encompass a range of craniofacial features. These include first/second branchial arch syndrome, oculo-auriculo-vertebral spectrum (OAVS), hemifacial microsomia (HFM) and Goldenhar syndrome (GS). However, there are no phenotypically distinct groups within the spectrum. Regardless, the treatment approach does not differ from the CFM population.

Etiology

  • Multifactorial

  • Association with maternal use of vasoactive medications, second trimester smoking, diabetes mellitus, multiple gestation, and use of reproductive technology

  • Heritable causes include autosomal dominant chromosomal deletions of 5q and duplication of the OTX2 gene on 14q23 ; autosomal recessive inheritance is rare

  • If the child is found to have an inherited or de novo chromosomal abnormality, genetic counseling is indicated. If a proband has CFM and no reported family history, the risk to siblings is 2%–3%.

Clinical features

CFM is a diagnosis of exclusion (no diagnostic criteria exist), based on physical exam findings ( Fig. 26.7 ) of unilateral or bilateral anomalies of:

  • Craniofacial clefts

  • Mandible: mandibular hypoplasia (micrognathia), retro-micrognathia, midface hypoplasia, ankylosis (limited opening of the mouth), malocclusion

  • Temporal and zygomatic bone: hypoplasia and associated down-slanting palpebral fissure

  • Ear: microtia (hypoplasia of the external ear), anotia (absence of external ear), aural atresia (absence of external ear and associated middle ear anomalies), conductive hearing loss

  • Facial musculature and soft tissue: facial asymmetry (hallmark even when bilateral), preauricular tags, pits (distributed along the ramus), masticatory and facial muscle hypoplasia, parotid gland hypoplasia

  • Facial nerve: the more severe the auricular deformities, the more likely facial nerve involvement

  • Axial skeleton: misaligned or fused vertebrae, hemivertebrae.

Fig. 26.7, Craniofacial microsomia. Several of the diagnostic features required for a diagnosis of craniofacial microsomia are present in this highly intelligent boy with multiple midline clefts (0–14, 1–13, 3, 7), with coloboma of the middle third of the right upper lid with right lower lid coloboma as part of a maxillary cleft, bilateral inferotemporal epibulbar dermoids and pre-auricular appendages distributed along the mandible. (B) CT reconstruction shows the frontal defect, orbital dystopia, maxillary cleft, and absence of right mandible and temporomandibular joint. (C) Multiple clefts are shown in red.

As many as 55% of cases have extracranial anomalies. Greater phenotypic severity may be correlated with extracranial involvement, including :

  • Cardiac: tetralogy of Fallot, ventricular septal defect, transposition great vessels, aortic arch anomalies

  • Renal: absent kidney, double ureter, hydronephrosis

  • Limb: radial or ulnar anomalies

  • CNS : microcephaly, encephalocele, hydrocephaly, hypoplasia of corpus callosum, Arnold–Chiari malformation.

Ocular and adnexal anomalies

Ocular anomalies and associated visual impairment are present in up to 70% of CFM cases and include :

  • Epibulbar dermoids ( Fig. 26.8 )

    Fig. 26.8, (A) Yellowish subconjunctival dermolipoma in the superotemporal fornix. (B) Epibulbar dermoid of the inferotemporal limbus with leading edge lipid infiltrate in the cornea. (C) This epibulbar dermoid had irritating hairs growing from it.

  • Dermolipoma (see Fig. 26.8 )

  • Eyelid coloboma, absence of lashes on the affected lid medial to the defect

  • Microphthalmia, anophthalmia

  • Strabismus/Duane’s syndrome

  • Downslanting palpebral fissures

  • Orbital dystopia

  • Anomalies of the lacrimal caruncle

  • Tortuous retinal vessels

Full orthoptic and eye examinations are warranted as part of the assessment of CFM. The patient should be followed up regularly and any amblyopia treated aggressively.

Treacher Collins syndrome

Treacher Collins syndrome (TCS) is the mandibulofacial dysostosis which is best studied. It is associated with Tessier 6, 7, and 8 clefts ( Figs. 26.9 and 26.10 ).

  • TCS is a ribosomopathy associated with at least three distinct genes, with high penetrance, variable expressivity, and no clear genotype–phenotype correlation.

  • The majority (90%) of cases are associated with mutations in TCOF1 gene on 5q32 encoding treacle , a putative nuclear phosphoprotein.

  • Additional causative mutations are in the RNA polymerase 1 subunit D, POLR1D gene on 13q12.2 and RNA polymerase 1 subunit C, POLR1C gene at 6p21.1, which like TCOF1 are involved in ribosome biogenesis required for neural crest cell formation and proliferation.

  • POLR1D and TCOF1 mutations are inherited in an autosomal dominant fashion, whilst mutations in POLR1C are recessive.

  • A considerable degree of inter- and intrafamilial variability in phenotypic severity is characteristic of TCS suggesting etiological contributions from genetic, environmental, and random events.

  • Incidence: approximately 1 in 50,000 live births (likely an underestimate given phenotypic variability).

Fig. 26.9, (A) Treacher Collins syndrome and Tessier cleft type 8 with choanal atresia and micrognathia, lower eyelid pseudocoloboma and external ear anomalies. (B) CT reconstruction demonstrating deficient lateral orbital wall, rim and floor with hypoplastic malar and zygomatic bones bilaterally. (C) Type 8 clefts shown in red.

Fig. 26.10, Treacher Collins syndrome. (A) Boy with Treacher Collins syndrome with mid-face hypoplasia, anti-mongoloid slant of palpebral fissures, pseudo-coloboma of the lateral lower lid, nasolacrimal duct obstruction, deafness, external ear anomalies. (B) Typical “fish-like” profile (absent nasofrontal angle), hypoplastic mandible, mouth breathing due to nasal airway obstruction.

Craniofacial features

  • Characteristic asymmetric hypoplasia of the maxilla, mandible, zygomatic complex together with inferolateral cleft (Tessier 6, 7, 8)

  • High arched palate which is frequently cleft

  • Micrognathia

  • Atresia of the external auditory canals and radiographically irregular or absent ossicle; conductive hearing loss is present in 40%–50%.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here