A pre-existing congenital anomaly is frequently the result of some genetic syndrome, which is composed of several recognizable phenotypic traits that occur together in a specific association. It is believed that this association of phenotypic traits is the result of a specific genetic defect. Currently a geneticist (or dysmorphologist) identifies the syndrome or association using the patient’s phenotype; however, in the future, more of these diagnoses will be made using molecular genetics to identify the patient’s chromosomal defect(s) which resulted in the particular phenotype and inheritance pattern. Some of the more common genetic disorders (syndromes) are diagnosed using conventional karyotyping, chromosomal microarray (CMA), or fluorescence in situ hybridization (FISH), performed on peripheral blood lymphocytes. Presumably the genetic basis for many syndromes and associations which do not currently have a known cause will be determined. The term association is used when a constellation of several recognizable phenotypic traits occur together, either without a known genetic cause, or with a variety of genetic causes. Unfortunately, the distinction between a syndrome and an association frequently is not clear, and these terms are routinely used interchangeably. Historically patients with genetic syndromes and associations received care from our colleagues in pediatric anesthesia. However, given the advances in pediatric anesthesiology and surgery over the last 50 years, these children with syndromes have grown up to become the parturient with a pre-existing congenital anomaly. As such, many of these women will require analgesia for labor and delivery, anesthesia for surgical deliveries, and/or non-obstetric therapeutic procedures performed during pregnancy. The implication is that obstetric anesthesiologists should expect to encounter patients with a syndrome more frequently. This chapter will first review the general approach to the pregnant patient with a genetic syndrome, and then review in more detail some syndromes associated with challenges in providing anesthetic care. Finally, a listing of selected syndromes associated with anesthetic management issues will be presented.

Airway management is always a central consideration for the obstetric anesthesiologist and many genetic syndromes are associated with an abnormal airway even before the pregnancy-induced changes to the airway occur. Some of the most common are syndromes associated with mandibular hypoplasia, including Crouzon syndrome (craniofacial dysostosis), Pierre Robin sequence (PRS), Treacher Collins syndrome (TCS) (mandibulofacial dysostosis), and Goldenhar syndrome (hemifacial microsomia). Other conditions include cleft lip and palate, high-arched palate with small mouth opening, cervical vertebral fusion limiting neck movement, and soft tissue obstruction from macroglossia or other causes. Eliciting a thorough preoperative history of airway issues, including snoring, airway obstruction while sleeping, and acute life-threatening events, is extremely important. Speaking with the parturient in order to identify and review any previous anesthetics and tracheal intubations is crucial, and whenever possible examining the previous anesthetic records or speaking to the previous anesthesiologist and/or otolaryngologist is also important. An examination of the airway for mouth opening, visualization of the pharynx, and soft palate, and neck range of motion, should only be performed by an experienced anesthesiologist. Finally, existing imaging studies such as chest, neck, and facial radiographs, CT scans, or MRI scans should be reviewed. It may be prudent to obtain airway imaging studies given that the radiation exposure risks to a properly shielded third-trimester fetus are minimal when compared to the risks to the parturient and her fetus in a “can’t intubate, can’t ventilate” scenario. A management plan, specific for this parturient’s difficult airway should be developed. Details of difficult airway management are presented in Chapter 24.

Many genetic syndromes include a cardiac component, and the importance of a thorough cardiac history and physical examination cannot be overemphasized. In the presence of an abnormal cardiac examination consisting most often of murmurs, the cardiac anatomy and pathophysiology must be understood, and any recent diagnostic studies such as echocardiography must be reviewed. Many of these women will be followed by a pediatric cardiologist who should be contacted in order to discuss specific issues related to this patient’s cardiopulmonary physiology. Echocardiographic studies should be interpreted by a cardiologist who is comfortable with congenital cardiac lesions, both repaired and unrepaired, and the pregnancy-induced changes in cardiopulmonary physiology. Some congenital anomalies are associated with cardiac conduction abnormalities mandating that an electrocardiogram be performed and reviewed. The pathophysiology and anesthetic management of common cardiac diseases (Ebstein’s anomaly, Eisenmenger’s syndrome, Long QT syndrome, and Wolff–Parkinson–White syndrome) are discussed in Chapter 30.

Some genetic syndromes include central or peripheral nervous systems anomalies, such as the neuromuscular disorders and neurocutaneous syndromes. For these types of anomalies, assessing the location of the lesion (e.g., lumbar epidural space, intracardiac, etc.), changes in intracranial pressure (ICP), and pre-existing peripheral neuromuscular deficits or paresthesias is extremely important. Other syndromes are associated with neurodevelopmental delay without obvious anatomic malformations. These neurodevelopmental changes may include a generalized lag in intellectual development, difficulties with gross or fine motor skills, abnormal speech and language development, and/or behavioral issues. It is important to assess the neurodevelopmental status of any parturient with a genetic syndrome as the chronologic age may differ significantly from the developmental age. This may make the induction of either neuraxial or general anesthesia challenging and require changes in the approach to preoperative preparation, communication, premedication, and/or the presence of the parturient’s support personnel. Many of these women will have experienced multiple medical encounters and interventions, and therefore may be very anxious in the pre-anesthetic period.

Some genetic syndromes are associated with limb abnormalities that make conventional intravenous (IV) access challenging. For these women, IV access should be obtained by an experienced anesthesiologist recognizing that the available options are limited and alternate sites may need to be utilized. These alternate sites may include scalp or anterior chest wall veins, external or internal jugular veins, or subclavian veins if the limbs are unavailable. As noted above, women with genetic syndromes have frequently had multiple hospitalizations and procedures making peripheral venous access potentially difficult or impossible, and further, the central veins may be thrombosed or stenotic from previous catheterizations. Noting the absence of typical superficial veins and the presence of cutaneous collaterals should increase the suspicion of difficult IV access. Consider additional studies, that is, ultrasound or MRI to plan for vascular access. In some cases, obtaining the assistance of an interventional radiologist may be warranted.

Deformities of the spine (scoliosis, kyphosis, etc.), large joints (hip dysplasia), and limbs (contractures) occur commonly in patients with genetic syndromes. Severe scoliosis or kyphosis should prompt an evaluation of the woman’s respiratory and cardiac status as this may initiate planning for postoperative ventilation and intensive care monitoring. Neuraxial anesthesia/analgesia may be technically challenging to administer and achieving an adequate block may be difficult when spread of the drug is impaired or unpredictable. Positioning of anesthetized patients with these problems must be done very carefully to avoid injury.

Devising a rational and safe anesthetic plan for parturients with rare disorders, or disorders with which the anesthesiologist is not familiar, may be challenging. Consulting a reference source (typically found in the pediatric anesthesia literature) will be necessary in order to become familiar with the issues involved in the specific syndrome. An excellent general source is the U.S. National Institutes of Health website which can be found at health.nih.gov/category/GeneticsBirthDefects (1). Other published resources are available; including both general review articles (2,3) and textbooks (4). It is becoming more prudent for the obstetric anesthesiologist to have these resources at hand since parturients with pre-existing congenital anomalies will be presenting more frequently. If the first presentation coincides with her time of delivery, a thorough literature search may not be possible. Recall that the patient, her family, and other caregivers may be extremely knowledgeable of the condition, and may be able to offer valuable information about how the parturient has previously responded to specific interventions.

For the obstetric anesthesiologist, a difficult airway to perform tracheal intubation is expected to result from pregnancy-induced changes to the normal airway; whereas our pediatric anesthesiologists expect syndromes which manifest mandibular anomalies, hemifacial microsomia, and/or micrognathia to be the cause; so they (and now we) must evaluate every patient in order to identify these abnormal airways. A number of craniofacial syndromes lead to mandibular anomalies (e.g., Apert syndrome), craniofacial dysostosis (e.g., Crouzon syndrome), hemifacial microsomia (e.g., Goldenhar syndrome), and micrognathia, including the Pierre Robin sequence and TCS. To date, only a few case reports exist addressing the anesthetic management of parturients with difficult airway syndromes, such as Crouzon syndrome (9) and TCS (10).

Apert syndrome is characterized by midfacial malformations such as hypoplasia or underdevelopment of the midface complex, craniosynostosis, and symmetric syndactyly of both hands and feet. Reportedly it occurs in approximately 1:60,000 births (11), approximately 20% to 30% of Apert patients are developmentally delayed, and many will need staged surgery in order to ameliorate their turribrachycephaly (cone-shaped skull) and midface hypoplasia. The craniofacial surgeries are intended to create a cranial vault that will accommodate the growing brain to ameliorate increases in ICP. However, in Apert’s patients, raised ICP also results from abnormal intracranial venous drainage, hydrocephalus, and airway obstruction; and is known to recur despite successful treatment (12). A number of factors contribute to their difficult airway. The midface grows more slowly and the forward development stops before 10 years of age; therefore, the deepest part of the face occurs just above the nose. Frequently the maxilla is hypoplastic causing a V-shaped maxillary arch. The soft palate tends to be long and thick, and the hard palate tends to be short resulting in a constricted, highly arched palate. Excess soft tissue occurs on the hard palate and its size increases with age. In addition, the midface hypoplasia causes a reduction in the caliber of the nasopharyngeal passages leading to difficult, noisy breathing (13). Up to 20% of children with craniofacial deformities will require tracheostomy for airway management, 48% of these are in craniosynostosis (e.g., Apert syndrome) patients. Nearly all of these children will be decannulated following staged surgical interventions (14). As would be expected following tracheostomy decannulation, there is an increased incidence of laryngomalacia, cartilaginous tracheal sleeves, and bronchomalacia in patients with Apert syndrome (15) and the upper airway obstruction and sleep apnea may lead to increasing airway compromise with age, unlike other anomalies such as Pierre Robin syndrome (16). An additional airway complication stems from the C-spine fusion which occurs in >60% of these patients, occurring most commonly at C3–C4 and C5–C6 (17). In a review of craniofacial airway abnormalities, Nargozian C notes that a small midface and proptosis may make mask ventilation challenging because of difficulties in obtaining a good mask fit, the tongue may occlude the oral airway by filling the relatively smaller oral cavity, and small nasopharyngeal passages increase the airflow resistance. Tracheal intubation becomes increasingly difficult as neck mobility decreases and smaller than expected endotracheal tubes (ETTs) may be necessary because of tracheal abnormalities (18). Issues for the anesthesiologist to address include both alterations in ICP, and airway management with abnormalities of the oropharynx, possibly the C-spine, and possibly distal airway changes following tracheotomy reversal.

Crouzon syndrome is characterized by maxillary hypoplasia, craniosynostosis, midface underdevelopment and ocular proptosis. It is estimated to occur in approximately 1:60,000 live births (19). All Crouzon syndrome patients have ocular proptosis. Their craniosynostosis, premature cranial suture fusion, leads to a variety of cranial malformations including brachycephaly (broad, short head), scaphocephaly (long, narrow head), trigonocephaly (triangular-shaped head when viewed from above), and cloverleaf skull (actually shaped like a cloverleaf). Many will need staged surgery in order to ameliorate their craniosynostosis and midface hypoplasia. A number of factors contribute to a difficult airway. As with Apert’s, the midface grows more slowly and forward development arrests. Both the length and width of the maxilla is reduced, and is pushed back farther than normal causing an arched appearance. In addition, the midface hypoplasia causes a reduction in the caliber of the nasopharyngeal passages leading to difficult, noisy breathing (13). Progressive C-spine fusion occurs in approximately 18% of these patients, most commonly at C2–C3 and C5–C6 and “butterfly” vertebrae are particularly prevalent (20). Sculerati et al. reported that 20% of children with craniofacial deformities will require tracheostomy for airway management, 48% of these are in craniosynostosis (e.g., Crouzon syndrome) patients. Nearly all of these children will be decannulated following staged surgical interventions (14). This would give rise to an increased incidence of cartilaginous tracheal sleeve, challenging mask ventilation, and decreasing neck mobility with increasing difficulties in tracheal intubation in patients with Crouzon syndrome. The overriding issue for the anesthesiologist to address is airway management with abnormalities of the oropharynx, possibly the C-spine, and possibly distal airway changes following tracheotomy reversal. In caring for a Crouzon’s parturient with preeclampsia and morbid obesity, Martin et al. reported successful use of an epidural catheter for labor analgesia. A cesarean delivery became necessary for obstetric indications. The patient experienced
progressive respiratory failure unresponsive to non-invasive ventilation. A general endotracheal anesthetic was indicated for respiratory failure; an awake fiberoptic intubation was only successful on the third attempt, with the use of an intubating laryngeal mask airway (AMA). Following delivery, an elective tracheostomy was performed for postoperative management of the patient’s respiratory failure (9).

Goldenhar syndrome, a hemifacial microsomia variant, arises from (typically unilateral) disordered developmental of the first and second branchial arches. It affects approximately 1 in 5,600 live births and is characterized by malformations of the external/middle ear with sensorineural hearing loss, the mandible (hypoplasia), the eye such as microphthalmus and epibulbar dermoids, and the vertebrae such as C-spine malformations, cervicothoracic scoliosis, and spina bifida occulta. The phenotypic spectrum of Goldenhar syndrome ranges from the very mild hemifacial asymmetry with preauricular ear tags or pits to severe facial deformity and mandibular hypoplasia (21). Goldenhar syndrome patients have a high incidence of congenital C-spine malformations, such as odontoid hypoplasia with C1–C2 instability significant enough to require surgical fusion (22). Difficulties with airway management and tracheal intubation occur commonly due to the mandibular hypoplasia, restricted mouth opening following jaw/temporomandibular joint reconstruction, C-spine instability or limited flexion following spinal fusion, and tracheal deviation with significant cervicothoracic scoliosis (18). Techniques such as fiberoptic or video-assisted laryngoscopy are frequently required for airway management (23,24). Congenital heart defects are reported in approximately 32% of these patients, frequently involving defects of the conotruncus (39%) and septum (32%) (25). Issues for the anesthesiologist to address include both airway management with abnormalities of the oropharynx, possibly the C-spine, and possibly distal airway changes following tracheotomy reversal as well as cardiac function with repaired or unrepaired congenital heart defects.

PRS is composed of retrognathia, glossoptosis, airway obstruction, and high-arched midline soft palate cleft in 50% (26). The defining criteria for PRS are variable; some do not require a cleft palate and others require respiratory compromise as part of the definition. This results in a wide range when estimating the incidence; but approximately 1 per 8,500 live births, with childhood mortality occurring in approximately 25%. Deformational (isolated) PRS, accounting for approximately 40%, results from physical forces in utero inhibiting normal mandible/palatal development. Isolated PRS has a good prognosis since post-natal mandibular catch-up growth is expected. Malformational PRS (part of another syndrome) has a less favorable prognosis and is most associated with Stickler syndrome and velocardiofacial syndrome. In the neonatal period, minimal intervention may be required for mildly affected patients whereas prone positioning, continuous positive airway pressure, endotracheal intubation, or tracheostomy may be required for patients with significant upper airway obstruction. Early in their life, a gastrostomy may be required as feeding difficulties are common and surgical repair of the cleft palate and mandible may significantly improve the outcome. Numerous airway management techniques for patients with PRS are reported in the literature. In the parturient with isolated PRS, an experienced anesthesiologist should perform the airway assessment, review prior anesthetic records, and contact prior anesthesiologists for information regarding this woman’s airway and intubation history, then develop a plan for managing her airway in the event that this becomes necessary.

TCS is a disorder of bilateral facial development, which affects approximately 1 in 50,000 live births. Characteristics of TCS include maxilla/zygoma/mandible hypoplasia, lateral downward palpebral fissure sloping, lower eyelid coloboma, external and middle ears malformation, and macrostomia, high palate, and a blind fistula between the angles of the mouth and ears. These patients require extensive bony facial reconstruction which spans decades, including the eyelid coloboma to protect the cornea, orbital and zygomatic reconstruction, external ear reconstruction, and mandibular advancement when bony growth is complete (26). Sculerati et al. reported that 20% of children with craniofacial deformities will require tracheostomy for airway management, 41% of these are in mandibulofacial dysostoses (e.g., TCS) patients. Nearly all of these children will be decannulated following staged surgical interventions (14). In children, the mask ventilation and tracheal intubation difficulties result from the mandibular hypoplasia and high-arched palate and these difficulties may become impossibilities when TMJ abnormalities are present as well (18). It should be presumed that tracheal intubation will become more difficult as the patient grows (27). Both successes and failures for numerous airway management techniques in TCS patients have been reported. In the TCS parturient, an experienced anesthesiologist should perform the airway assessment, review prior anesthetic records and contact prior anesthesiologists for information regarding this woman’s airway and intubation history (recalling that the level of difficulty is expected to increase from the prior intubation), and then develop the plan for managing her airway in the event that this becomes necessary. Morillas et al. reported successfully inserting a LMA-Fastrach® for an emergent cesarean section under general anesthesia; however, blind endotracheal intubation was unsuccessful and the surgery was completed using the LMA (10).

Although obstetric anesthesiologists care for parturient’s with each of these syndromes, only Noonan syndrome and the Uhl anomaly are discussed, since numerous reports addressing the anesthetic management for labor and delivery in these patients exist. Other cardiac syndrome, such as Ebstein’s anomaly and Long QT syndrome, are covered in Chapter 30 of this text.

Noonan syndrome, occurring in approximately 1:2,500 live births, is characterized by cardiac defects and distinctive facial features including hypertelorism with downslanting palpebral fissures, ptosis, and low-set posteriorly rotated ears. Cardiovascular manifestations of this syndrome include pulmonary valve stenosis (60%), hypertrophic cardiomyopathy (20%), atrial septal defects (10%), VSDs (5%), and patent ductus arteriosus (3%) (28). Airway abnormalities may include a high-arched palate and micrognathia, which combined with a prominent trapezius muscle leading to neck webbing, may result in a challenging airway to manage (6). Other defects include a “shield chest” and abnormal lymphatic drainage resulting in lymphedema (28). Scoliosis, usually thoracic, is present in approximately 30% of these patients; (29) which combined with a “shield chest” and the changes in functional residual capacity during pregnancy may significantly compromise pulmonary function. Spinal deformities may contribute to difficulty placing an epidural catheter or controlling the block level in those patients with a lumbar spinal curvature may be technically challenging (30). Although these patients may have coagulation or platelet defects including factor XI deficiency, von Willebrand’s disease, or thrombocytopenia, (31) which should be considered before placing a neuraxial
block, there are numerous reports of successful delivery under spinal anesthesia, (30,32,33) epidural anesthesia/analgesia, (34) combined spinal–epidural anesthesia, (35) and general anesthesia, where the difficult airway was managed by performing an awake fiberoptic intubation (36,37). Dadabhoy et al. reported a failed lumbar epidural placement due to technical difficulty locating the epidural space although a spinal was placed without difficulty; (30) and Grange et al. reported the successful use of 1-deamino-8-D arginine vasopressin (DDAVP) to treat post-partum bleeding attributed to coagulopathy (37). Previously there was concern of MH susceptibility based on a single case report of a possible association; however, there are no other reports or genetic studies establishing a link and many reports of successful anesthetics using both halothane and succinylcholine (38).

Uhl anomaly (arrhythmogenic right ventricular cardiomyopathy [ARVC]) is a familial disease characterized by right ventricular structural and functional abnormalities that result from the replacement of myocardial tissue by fat and fibrous tissue which seems to progress (including possible involvement of the left ventricle) following an inflammatory reaction. Its estimated prevalence is 1:5,000, and it occurs 3 times more frequently in men. The clinical presentation involves phases. No symptoms occur during the “concealed phase”; however, these patients are at risk for sudden cardiac death during exertion. During the “electrical phase,” symptomatic arrhythmias occur and morphologic abnormalities are discernable with conventional imaging. Disease progression may result in biventricular heart failure ultimately resembling dilated cardiomyopathy (39). This anomaly was identified post-mortem in 35% of patients during a retrospective analysis of unexpected sudden cardiac death in healthy patients related to surgery and/or anesthesia and included women undergoing cesarean delivery (40). Treatment for the arrhythmias in ARVC include anti-arrhythmic drugs and/or implantable cardioverter-defibrillator (ICD); however, for preventing sudden death, the ICD is superior to anti-arrhythmic drugs (41). In order to avoid labor pain-induced tachycardia and to facilitate an instrumented delivery, the successful use of epidural analgesia has been reported (42,43). In the case reported by Doyle et al, an implantable cardiac defibrillator was placed at 21 weeks’ gestation (42). Successful use of general anesthesia for cesarean delivery has also been reported (44).

Epidermolysis bullosa (EB), a group of bullous skin disorders, is characterized by blister formation resulting from mechanical trauma. EB is generally divided into three major types: EB simplex, involving only the epidermis; junctional EB, involving the basement membrane; and dystrophic EB, involving primarily the dermis (45). Severity of the clinical manifestations is variable, with dystrophic EB (DEB) being the most severe form. Most DEB patients will have blisters and wounds presenting at birth or shortly thereafter. The blister size is variable and the healing process leads to atrophic scarring with contracture development, occurring most commonly on the hands, feet, elbows, and knees (46). Friction, from scratching or other mechanical forces, is very damaging in EB. Oral, pharyngeal, and esophageal blistering is common in EB, leading to mouth and tongue contractures. Extremity contractures can cause scarring that is severe enough to create pseudosyndactyly. Corneal scarring may also occur. Treatment for EB involves avoiding friction and shearing forces by using special clothing and feeding techniques, blister drainage and treatment with silver sulfadiazine for large infected lesions, special dressings made of hydrofiber foam and coated with silicone, and topical corticosteroids.

For parturients with EB, the most important anesthetic concept is that friction and shearing forces, not direct pressure, cause new bullae formation. Neck contractures and pharyngeal bullae present distinct challenges to airway management; therefore, assessment of the airway should be performed by an experienced anesthesiologist. Fortunately, the veins are typically easy to visualize and cannulate. Minimizing the number of transfers for these patients is prudent since sliding would cause shearing forces between the patient and both the stretcher and operating room bed which would contribute to bullae formation. Assiduously avoiding adhesives when attaching monitors, IV cannulae, or airway devices are also recommended. Peripheral IV cannulae may be secured using a single suture. Other suggested maneuvers include use of a clip on pulse oximetry probe, cutting away the adhesive portion of the ECG electrode and securing the gel portion to the skin with paraffin gauze or a gelpad, padding the skin with Webril® soft gauze before applying a non-invasive blood pressure cuff, avoiding both nasopharyngeal and rectal temperature probes, thoroughly lubricating the facemask with petroleum jelly or protecting it with paraffin gauze, and taking care to avoid shearing forces on the skin between the facemask and the patient’s face and neck. Generally, orotracheal intubation is preferred, using an ETT that is one-half size smaller than normal; with gentle laryngoscopy the incidence of new laryngeal or pharyngeal bullae is low (46). Anticipated difficult airway management, with contractures or severe intraoral bullae, requires careful planning and may include the availability of videolaryngoscopy, fiberoptic bronchoscopy, and LMAs. A well-lubricated LMA can be used for airway maintenance, with little risk of new severe intraoral bullae formation, but airway maintenance using a facemask for long time periods should be avoided. Non-depolarizing muscle relaxants may be used, but succinylcholine should be avoided. Standard IV induction agents, maintenance agents, and both opioid and regional anesthesia (epidural catheters should be secured using a soft silicone-type tape) have been safely used in EB patients. Emergence from anesthesia and tracheal extubation must be carefully done, taking care to avoid shearing forces on the face; intraoral suctioning must also be gently done. Avoiding the use of a conventional facemask for supplemental oxygen administration in postanesthesia recovery is important; the oxygen concentration may be increased by blowing humidified oxygen over the face with 22 mm corrugated oxygen tubing. The patient should be evaluated for the formation of new bullae postoperatively and the anesthesia team should communicate with the patient’s dermatologist regarding any changes in treatment plan after the anesthetic. There are published reports of successful vaginal deliveries without anesthesia, (47) and cesarean deliveries performed under general endotracheal anesthesia, (48) lumbar epidural anesthesia, (49,50) and spinal anesthesia (47,49,51).

Phakomatoses (neuroectodermal diseases) are characterized by ipsilateral or midline skin lesions, central nervous system (CNS) (often neuraxial) neoplasm’s or arteriovenous malformations (AVMs), and ocular anomalies. Craniofacial
asymmetry, seizures, intracranial hypertension are also characteristics of most phakomatoses and some (Tuberous Sclerosis, Sturge–Weber) are associated with congenital heart defects while others (von Hippel–Lindau [VHL], Neurofibromatosis) are uniquely associated with pheochromocytomas (52).

Neurofibromatosis (NF) or von Recklinghausen disease occurs in both peripheral nervous system and CNS form. NF Type 1, the most common phacomatosis with an estimated prevalence of 1:5,000, is characterized by café au lait macules, schwannomas or neurofibromas involving cranial and peripheral nerves, axillary/inguinal freckling, optic gliomas, Lisch nodules (hamartomas of the iris), and a distinctive osseous lesion. In NF-1, the neurofibromas are generally benign tumors that most commonly affect the cranial nerves (most commonly the trigeminal nerve, CN-5) with symptoms resulting from compression. Nearly all adults have Lisch nodules (hamartomas of the iris), and optic nerve gliomas, which lead to visual defects, occur in 15% to 20% of NF-1 patients. Other CNS findings include aqueductal stenosis, Chiari malformations, as well as cervical and occipital AVMs. Skin manifestations include café au lait spots, freckles, and cutaneous neurofibromas while visceral lesions include pheochromocytomas and intestinal, hepatic, or bladder neurofibromas. NF Type 2 has an estimated prevalence of 1:50,000 with the most prominent manifestation being acoustic (usually bilateral) neuromas leading to progressive hearing loss followed by tinnitus and imbalance. Visual changes occur with compression of cranial nerve 6 (CN-6), while facial numbness or weakness can occur with compression of CN-5 and cranial nerve 7 (CN-7), respectively. CNS tumors, such as gliomas, ependymomas, and meningiomas occur. Skin manifestations, such as café au lait spots and cutaneous neurofibromas, are less common than in NF-1 (53). Some of the issues followed by the obstetrician during the pregnancy include changes in tumor character (54,55,56), number and/or size (57), and/or obstructing delivery (58,59); tumor hemorrhage (60,61,62); hypertensive disorders both with (63) and without (64) pheochromocytoma, which span gestational hypertension, pre-eclampsia (65), HELLP syndrome (66), eclampsia (67), and renovascular hypertension (66). Issues for the experienced anesthesiologist to consider when selecting either regional or general anesthesia for these women start with the pregnancy-associated increase in both number and size of the neurofibromas attributed to NF-1 tumor expression of the progesterone receptor (68). The basis for choosing general over regional anesthesia would include symptoms and/or imaging studies suggesting neuraxial tumor growth, significant coagulopathy, or pheochromocytoma. Although successful general endotracheal anesthetics have been administered (61,69,70), a number of issues should be considered. First, airway management may be difficult; oral neurofibromas occur, commonly causing macroglossia, which are generally sessile and may bleed following trauma; tumors occurring in the neck or larynx, causing dysphagia, hoarseness, and/or stridor, may compromise the airway (71); and C-spine abnormalities, many asymptomatic, may be present in nearly 44% of patients (72). Tracheostomy has been required following complete airway obstruction following induction of anesthesia (73) and failed fiberoptic intubation (74). Second, cardiopulmonary compromise may occur with spontaneous hemothorax (62), mediastinal masses (55,56,75), and elevated blood pressures from renal artery stenosis (66,76), or pheochromocytoma (63). Abnormal responses to both depolarizing and non-depolarizing neuromuscular blockade have been reported (77,78). However, Richardson et al. demonstrated minimal risk of abnormal response to either drug class in patients with NF-1 with appropriate dosing (79). Tumor growth occurs in both NF-1 and NF-2 in response to hormonal changes, making neuraxial imaging before performing a regional anesthetic strongly recommended (80). Following negative imaging studies, epidural analgesia/anesthesia has been used successfully in both NF-1 (81) and NF-2 (80) parturients; however, epidural hematoma has been reported as a complication (82). Rasko et al. demonstrated in vitro that normal platelet aggregation in NF-1 patients requires higher collagen concentrations (83), although it is unclear that this finding changes the risk of placing a neuraxial block. Further, Lighthall et al. reported the successful use of DDAVP to correct an intraoperative coagulopathy in a woman with NF-1, although the authors express their uncertainty that DDAVP alone resolved the bleeding (84).