*4.3.3 Pfeiffer syndrome*

*Overview*: also known as acrocephalosyndactyly Type V, Pfeiffer syndrome involves sagittal craniosynostosis, maxillary retrusion of variable degrees, and soft tissue syndactyly. Mental retardation and congenital heart disease are commonly associated (**Figure 3**).

*Genetics*: it is autosomal recessive, with some cases presenting as de novo/sporadic mutations.

*Incidence*: extremely rare.

*Pathophysiology*: the genetic mutation involves the FGFR-1 and FGFR-1 genes involved in fetal mesenchymal integrity of the tissue that forms the bones, resulting in premature bony maturation and closure of the sutures, along with accelerated ossification of the calvaria.

*Clinical considerations*: much like Crouzon syndrome, Pfeiffer syndrome is commonly characterized by maxillary hypoplasia and flat facies, along with proptosis and hypertelorism. Strabismus is commonly present. This condition is linked to mild craniosynostosis and mainly involving the coronal and sagittal sutures. Limb findings are associated with broad thumb, great toe, and polysyndactyly. These

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patients also present with unpredictable degrees of hearing loss, mainly moderate to severe in most patients. Also, common findings are choanal atresia and cleft palate. Occasional associations include laryngomalacia, tracheomalacia, and bronchomalacia, along with fused cervical spine at varying levels in 30% of Pfeiffer syndrome patients. Other less common associations include Arnold-Chiari malformation,

*Airway and anesthetic implications*: the degree of mental retardation will dictate the difficulty of parental separation when shifting the patient to the operating room. Special consideration must include protecting the eyes in the presence of proptosis. Difficulty in airway management is to be expected and anticipated. Maintenance of spontaneous ventilation and oxygenation until the airway is secured is of vital importance. Alternate airway management techniques must be prepared and available (video laryngoscope, fiberoptic intubation, and laryngeal mask airway). Depending on the degree of congenital cardiac anomalies present, special considerations are to be undertaken. A large bore intravenous or central venous access is to be considered for more involved procedures, along with readiness for blood transfusion. In the setting of increased intracranial pressure, special consideration includes the maintenance of cerebral perfusion pressure intraopera-

*Overview*: also known as mandibulofacial dysostosis or Franceschetti-Zwahlen-Klein syndrome, Treacher Collins syndrome (TCS) is recognized as being one of the most severe craniofacial malformation disorders and one of the most challenging airways encountered by an anesthesiologist [26]. Hallmark features include malar and mandibular hypoplasia, bilateral anotia or microtia often associated with bilateral conductive hearing loss, antimongoloid slanting of the eyelid fissures and lower lid colobomas. Although this syndrome was firstly described in 1846 by Thompson, and reported as a congenital disease with coloboma of the lower eyelids by George Andreas berry in 1889, its name is associated to a British ophthalmologist Edward Treacher Collins, who, in 1990 published a case report of two patients with these

*Genetics*: known to be a very rare genetic disease, TCS results from a mutation on the TCOF1 gene in most individuals but rare cases were reported secondary to mutation of the POLR1C or POLR1D gene. It is an autosomal dominant inherited disorder. Only about 1% of cases are inherited in an autosomal recessive pattern [28]. *Incidence*: it has a prevalence of about 1 in 50,000 live births, without predisposi-

*Pathophysiology*: this is a defect of the neural crest formation which affects the first and second branchial arches, grooves, and pouches during the second month of intrauterine life resulting in an oto-mandibular dysplasia associated with other

*Clinical considerations*: the clinical features associated with Treacher Collins syndrome involve the head and neck and appear to be bilateral with relatively symmetrical distribution. They are variable in severity, mainly including zygomatic, mandibular and maxillary hypoplasia, micrognathia, external ear malformations, hearing loss, high arched palate, antimongoloid slanting of the eyelid fissures, colobomas, total or partial absence of lower eyelashes, and midface bones hypoplasia resulting in a pathognomonic bird-like face appearance with a protruded nose and small rounded face. It may also impact the oral cavity with dental malocclusion and anterior open bite. The hypoplasia of the mandible is more severe at the condyle than at the ramus and the body, which could be potentially responsible for temporomandibular joint

*DOI: http://dx.doi.org/10.5772/intechopen.93426*

**4.4 Treacher Collins syndrome (TCS)**

ocular and periorbital sequelae (**Figure 4**).

tion for sex or race.

craniofacial anomalies [28].

imperforate anus, and congenital heart disease [6, 7, 17].

tively, with a keen eye on mean arterial blood pressure [1, 24, 25].

**Figure 3.** *Images of children with type 1,2,3 Pfeiffer syndrome [23].*

#### *An Approach to the Airway Management in Children with Craniofacial Anomalies DOI: http://dx.doi.org/10.5772/intechopen.93426*

patients also present with unpredictable degrees of hearing loss, mainly moderate to severe in most patients. Also, common findings are choanal atresia and cleft palate. Occasional associations include laryngomalacia, tracheomalacia, and bronchomalacia, along with fused cervical spine at varying levels in 30% of Pfeiffer syndrome patients. Other less common associations include Arnold-Chiari malformation, imperforate anus, and congenital heart disease [6, 7, 17].

*Airway and anesthetic implications*: the degree of mental retardation will dictate the difficulty of parental separation when shifting the patient to the operating room. Special consideration must include protecting the eyes in the presence of proptosis. Difficulty in airway management is to be expected and anticipated. Maintenance of spontaneous ventilation and oxygenation until the airway is secured is of vital importance. Alternate airway management techniques must be prepared and available (video laryngoscope, fiberoptic intubation, and laryngeal mask airway). Depending on the degree of congenital cardiac anomalies present, special considerations are to be undertaken. A large bore intravenous or central venous access is to be considered for more involved procedures, along with readiness for blood transfusion. In the setting of increased intracranial pressure, special consideration includes the maintenance of cerebral perfusion pressure intraoperatively, with a keen eye on mean arterial blood pressure [1, 24, 25].

## **4.4 Treacher Collins syndrome (TCS)**

*Special Considerations in Human Airway Management*

the possibility of venous air embolism [1, 21, 22].

*4.3.3 Pfeiffer syndrome*

associated (**Figure 3**).

*Incidence*: extremely rare.

ossification of the calvaria.

radic mutations.

*Airway and anesthetic implications*: Serious airway examination is necessary in this condition. Maxillary hypoplasia may lead to poor mask fit, and visualization of the vocal cords can be difficult with standard laryngoscopy. Choanal atresia must be assessed prior to anesthesia induction. Cervical spine fusion must be evaluated preoperatively, as it can lead to difficulty with neck extension. One must also be mindful of intracranial pressure in the setting of progressive hydrocephalus and chronic tonsillar herniation. Depending on the degree of mental retardation, separation from family may pose a challenge. Difficult airway management is to be expected. Maintenance of spontaneous ventilation and oxygenation is necessary until the airway is secured. Alternate airway management techniques must be planned and pre-arranged (video laryngoscope, fiberoptic intubation, and laryngeal mask airway). A pre-operative echocardiograph is necessary, along with certain intraoperative management measures depending on the cardiac anomaly involved. Special consideration must include eyes protection in the setting of proptosis. Large bore intravenous access must be considered for major surgeries. In case of cranial vault reconstruction for craniosynostosis repair, the anesthesiologist must be mindful of

*Overview*: also known as acrocephalosyndactyly Type V, Pfeiffer syndrome involves sagittal craniosynostosis, maxillary retrusion of variable degrees, and soft tissue syndactyly. Mental retardation and congenital heart disease are commonly

*Genetics*: it is autosomal recessive, with some cases presenting as de novo/spo-

*Pathophysiology*: the genetic mutation involves the FGFR-1 and FGFR-1 genes involved in fetal mesenchymal integrity of the tissue that forms the bones, resulting in premature bony maturation and closure of the sutures, along with accelerated

*Clinical considerations*: much like Crouzon syndrome, Pfeiffer syndrome is commonly characterized by maxillary hypoplasia and flat facies, along with proptosis and hypertelorism. Strabismus is commonly present. This condition is linked to mild craniosynostosis and mainly involving the coronal and sagittal sutures. Limb findings are associated with broad thumb, great toe, and polysyndactyly. These

**164**

**Figure 3.**

*Images of children with type 1,2,3 Pfeiffer syndrome [23].*

*Overview*: also known as mandibulofacial dysostosis or Franceschetti-Zwahlen-Klein syndrome, Treacher Collins syndrome (TCS) is recognized as being one of the most severe craniofacial malformation disorders and one of the most challenging airways encountered by an anesthesiologist [26]. Hallmark features include malar and mandibular hypoplasia, bilateral anotia or microtia often associated with bilateral conductive hearing loss, antimongoloid slanting of the eyelid fissures and lower lid colobomas. Although this syndrome was firstly described in 1846 by Thompson, and reported as a congenital disease with coloboma of the lower eyelids by George Andreas berry in 1889, its name is associated to a British ophthalmologist Edward Treacher Collins, who, in 1990 published a case report of two patients with these ocular and periorbital sequelae (**Figure 4**).

*Genetics*: known to be a very rare genetic disease, TCS results from a mutation on the TCOF1 gene in most individuals but rare cases were reported secondary to mutation of the POLR1C or POLR1D gene. It is an autosomal dominant inherited disorder. Only about 1% of cases are inherited in an autosomal recessive pattern [28].

*Incidence*: it has a prevalence of about 1 in 50,000 live births, without predisposition for sex or race.

*Pathophysiology*: this is a defect of the neural crest formation which affects the first and second branchial arches, grooves, and pouches during the second month of intrauterine life resulting in an oto-mandibular dysplasia associated with other craniofacial anomalies [28].

*Clinical considerations*: the clinical features associated with Treacher Collins syndrome involve the head and neck and appear to be bilateral with relatively symmetrical distribution. They are variable in severity, mainly including zygomatic, mandibular and maxillary hypoplasia, micrognathia, external ear malformations, hearing loss, high arched palate, antimongoloid slanting of the eyelid fissures, colobomas, total or partial absence of lower eyelashes, and midface bones hypoplasia resulting in a pathognomonic bird-like face appearance with a protruded nose and small rounded face. It may also impact the oral cavity with dental malocclusion and anterior open bite. The hypoplasia of the mandible is more severe at the condyle than at the ramus and the body, which could be potentially responsible for temporomandibular joint

#### **Figure 4.**

*Treacher Collins syndrome with characteristic facial features including downward and laterally slanting palpebral fissures, paucity of lashes and lack of naso-frontal angle, bird like appearance, micrognathia, microtia (deformed pinna), macrostomia, and large tongue [27].*

dysfunction and mouth opening limitation. TCS is associated with Cleft Palate in 30% of the cases, and pharyngeal hypoplasia is commonly associated as well. All these anomalies can disrupt several functions like breathing, swallowing, chewing, and speech. Systemic manifestations, namely cardiac, renal, and skeletal, especially cervical vertebral defects, may also be observed [1, 4, 6, 7, 17].

*Airway and anesthetic implications*: Treacher Collins syndrome (TCS) was firstly reported as a hazard for general anesthesia in 1963 by Edward Ross due to the difficulty in maintaining a free and adequate airway. Several associated mechanisms are the cause, namely mandibular hypoplasia, micrognathia, retrognathia, posterior displacement of the bulky tongue, and the pharyngeal hypoplasia, resulting in a small and narrow retromandibular space [29, 30]. The presence of a temporomandibular joint abnormality or a small mouth aperture may further worsen the case. Thus, upper airway obstruction is common at induction of anesthesia and may require an airway manual maneuver (a two-hand mask ventilation, chin lift, and jaw thrust) and insertion of an oropharyngeal/nasopharyngeal airway. If unsuccessful, insertion of a supraglottic airway device such as a laryngeal mask airway before intubation is indicated. In addition, the failure rate of direct intubation is extremely high owing to the difficulty in alignment of the three axes (oral, pharyngeal, and laryngeal axes), which complicates further the visualization of the glottis. The degree of severity worsens with increasing age mainly because of the decreased mandibular growth.

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airway and guide the choice of the best airway management plan.

A rigorous and warily planned algorithm is the success key in the management of the airways in children with Treacher Collins syndrome. Consultation of previous anesthesia records is of valuable aid, and a meticulous airway reassessment is required. A preoperative 3D tomographic images help assess anatomical features of the upper

A laryngeal mask airway (LMA) is indicated for short and superficial procedures. But, whenever tracheal intubation is required, the spontaneous ventilation during anesthetic induction must be maintained until securing the airways. Fiberoptic intubation represents the preferred technique. It is facilitated by application of traction on the tongue, and a jaw thrust with a backward-upward-rightward pressure ("BURP") maneuver. Awake fiberoptic intubation is challenging in the pediatric population owing to the lack of cooperation. Other several techniques have been successfully used for tracheal intubation, namely fiberoptic intubation through LMA, fiberoptic-assisted laryngoscopy, blind nasal intubation, retrograde intubation, Shikani Optical Stylet (SOS), indirect videolaryngoscopy with GlideScope Ranger, Airtraq optical laryngoscope, Airway Scope or C-MAC videolaryngoscope with D-Blade, and tracheostomy as the last option. The use of TruView EVO2 laryngoscope for reintubation after accidental extubation in a

TCS patients undergoing major surgical procedures involving the airway should be kept intubated and sedated in the intensive care unit (PICU) until subsidization of the edema. For short surgical superficial procedures not involving the airway, extubation may be attempted based on the clinical judgment of the anesthesiologist and the hospital set up. Before extubation, a nasopharyngeal airway must be inserted and maintained during the postoperative period in order to prevent upper

*Overview*: Goldenhar's syndrome, also called Facio-auriculo-vertebral syndrome or Oculo-Auriculo-Vertebral syndrome, is a variant of hemifacial microsomia disorders that affect the eye, ear, nose, lip, soft palate, and mandible, and often associated with vertebral and cardiac anomalies. It was initially reported in 1952 by a Belgian-American ophthalmologist Maurice Goldenhar. In 1963, Gorlin introduced the term "Oculo-Auriculo-Vertebral syndrome" due to the presence of associated

*Genetics*: the exact etiology remains unclear. Most cases are sporadic, but some

*Pathophysiology*: this hemifacial microsomia is caused by the underdevelopment of the first and second branchial arches during the 4th week of gestation resulting in craniofacial anomalies, ocular anomalies, vertebral anomalies, and cardiac

*Clinical considerations*: Goldenhar's syndrome (GS) is a multisystem syndrome with a wide spectrum of clinical features. Craniofacial anomalies are unilateral in 90% of the cases and include mandibular hypoplasia, hypoplastic zygomatic arch, micrognathia, macrostomia, external and middle ear malformations (microtia, preauricular appendages, and atresia) often with sensorineural hearing loss, and eye anomalies (epibulbar dermoids, lipodermoids, microphthalmos, and coloboma). Nevertheless, in 10% of cases both facial sides may be affected with one side typically more affected than the other. Oral cavity anomalies like palate anomalies

rare familial cases were reported suggesting autosomal dominant or recessive

births, affecting males predominantly. Male to female ratio is 2:1.

*Incidence*: Goldenhar's syndrome occurs in about 1 in 3000 to 1 in 5000 live

*DOI: http://dx.doi.org/10.5772/intechopen.93426*

neonate with TCS was also reported [26, 31].

airway obstruction.

inheritance [33].

defects.

**4.5 Goldenhar's syndrome (GS)**

vertebral anomalies (**Figure 5**).

#### *An Approach to the Airway Management in Children with Craniofacial Anomalies DOI: http://dx.doi.org/10.5772/intechopen.93426*

A rigorous and warily planned algorithm is the success key in the management of the airways in children with Treacher Collins syndrome. Consultation of previous anesthesia records is of valuable aid, and a meticulous airway reassessment is required. A preoperative 3D tomographic images help assess anatomical features of the upper airway and guide the choice of the best airway management plan.

A laryngeal mask airway (LMA) is indicated for short and superficial procedures. But, whenever tracheal intubation is required, the spontaneous ventilation during anesthetic induction must be maintained until securing the airways. Fiberoptic intubation represents the preferred technique. It is facilitated by application of traction on the tongue, and a jaw thrust with a backward-upward-rightward pressure ("BURP") maneuver. Awake fiberoptic intubation is challenging in the pediatric population owing to the lack of cooperation. Other several techniques have been successfully used for tracheal intubation, namely fiberoptic intubation through LMA, fiberoptic-assisted laryngoscopy, blind nasal intubation, retrograde intubation, Shikani Optical Stylet (SOS), indirect videolaryngoscopy with GlideScope Ranger, Airtraq optical laryngoscope, Airway Scope or C-MAC videolaryngoscope with D-Blade, and tracheostomy as the last option. The use of TruView EVO2 laryngoscope for reintubation after accidental extubation in a neonate with TCS was also reported [26, 31].

TCS patients undergoing major surgical procedures involving the airway should be kept intubated and sedated in the intensive care unit (PICU) until subsidization of the edema. For short surgical superficial procedures not involving the airway, extubation may be attempted based on the clinical judgment of the anesthesiologist and the hospital set up. Before extubation, a nasopharyngeal airway must be inserted and maintained during the postoperative period in order to prevent upper airway obstruction.
