Background

The Klippel–Feil anomaly (KFA) is characterized by the congenital fusion of two or more cervical vertebrae. In its most severe form, there is massive cervical vertebral fusion with a short neck, limited head movement, and a low posterior hairline.2,12,15,21,23,29,37,39,55 Gorlin and Cohen have pointed out that the term vertebral fusion is not accurate because this condition results from the failure of the normal segmentation process.²⁴ Vertebral fusion can be traced to the third embryonic week when the segmentation of the mesodermal somites normally takes place.

KFA was described as early as the 16th century, and similar anatomic findings in the second and third cervical vertebrae have been found in an Egyptian mummy that has been dated to be from about 500 B.C. In 1912, Maurice Klippel and Andre Feil described the postmortem findings of a 46-year-old French tailor who had a short, immobile neck with massive fusion of cervical and upper thoracic vertebrae.³⁴ In 1919, Feil added reports of 13 additional patients, 12 of whose cases had been reported previously.

In 1967, Gunderson and colleagues categorized KFA in accordance with three morphologic types of cervical vertebral fusion.²⁷ Type I consists of the massive fusion of many cervical and upper thoracic vertebrae into bony locks. Type II involves fusion at only one or two interspaces. Type III comprises both cervical fusion and lower thoracic or lumbar fusion.

It is important to remember that KFA is morphologically and etiologically heterogeneous. This was further documented by Gunderson, who used Feil’s classification system to review inheritance patterns.²⁸ Type I cases have almost all been sporadic, with a female predilection. Type II is transmitted as an autosomal dominant disorder. For Type III, an autosomal recessive mode of inheritance has been suggested.

Various authors differ with regard to their interpretation of what constitutes KFA.9,61–63 A malformation with the triad of a short neck, a low posterior hairline, and a painless restriction of cervical motion characterizes just over 50% of patients. The functional limitation of the neck range of motion is the most consistent finding. Despite frequent sparing of the atlanto–axial joint, rotation is typically impaired more than flexion or extension is, with the latter exhibiting a range of more than 90 degrees, even with only one open disc space.

With the severe form of KFA (Type I deformity), there is massive cervical vertebral fusion, and the head seems to sit directly on the thorax, without any interposition of the neck. The flared trapezius muscles extend from the mastoid areas to the shoulders, which produces a pterygium-like effect. Posteriorly, the hairline extends to the shoulders. Cervical foreshortening (rather than overgrowth of the scalp) displaces the hairline and is accompanied by webbing of the neck.

Diverse ocular anomalies are frequently found, with the impairment of extraocular movement being the most frequent.⁵⁷Convergent strabismus and, less commonly, horizontal nystagmuses are seen. From 25% to as many as 50% of affected children exhibit hearing loss that may be sensorineural, mixed, or conductive.^{11,16,39,51,60,64} Clefting of the secondary palate is present in 15% to 20% of patients.^10,58,59 The combination of hearing loss and cleft palate explains the hypernasality that has been documented in approximately 15% to 20% of patients with KFA. Congenital heart defects occur in 4.2% of patients, which is in stark contrast with the prevalence of 0.6% among all live births in the general population.⁵⁰ Ventricular septal defect is the most common heart anomaly documented,⁴³ and vascular anomalies may also occur.^5,6 Congenital urinary anomalies are a frequent finding, with unilateral renal agenesis occurring in 28% of patients.¹⁴ Genital anomalies (e.g., vaginal agenesis) also occur at a higher frequency in these patients than they do in the general population.^40,42 Neurologic disturbances that consist of involuntary dyskinesis, spasticity or hyperreflexia, syringomyelia, syringobulbia, disc protrusion, osteophytes, and narrowing at the level of the craniovertebral junction have been reported..^{3,20,22,36,44,48} Nagib and colleagues found patients with KFA with two unsegmented blocks of bone, cervical stenosis, or cranial involvement to be at highest risk for neurologic disturbances.^45–47 Those with only one unsegmented bone were found to be at low risk for cervical injuries. The flared trapezius muscles associated with KFA give the individual an appearance that may be similar to that seen in patients with Turner or Noonan syndrome.^8,13,18,38 The cervical vertebral anomalies and other defects of the spine that occur within the oculo–auriculo–vertebral spectrum may also be confused with those of KFA.^{4,7,8,25,32,33,35,49,52,54,56}

Author’s Approach to Facial Reconstruction in Patients with Klippel–Feil Anomaly

The surgical management of KFA requires the accurate diagnosis of each specific problem (see Fig. 1-2).^17,26,31 Middle-ear infections should be treated promptly, and any hearing deficit should be aided whenever possible. Clefting of the secondary palate should be repaired in the usual way. Hypernasality as a result of inadequate soft palate motion after initial palate repair should be recognized and treated with a pharyngoplasty. Extraocular muscle abnormalities are managed with eye patching, spectacles, and eye-muscle surgery, as appropriate. The recognition of cardiovascular and genitourinary malformations should lead to medical treatment and surgery. Cervical spine instability requires the decompression of any nerve impingement and the fusion of unstable segments. Unfortunately, the typical fixed neck curvature observed in patients with KFA cannot safely be straightened.

The aim of the reconstructive procedures used to correct a webbed neck is to create as normal a neck contour as possible with a symmetrical posterior hairline while avoiding obvious scarring.¹ It is important to recognize that not all patients with webbed necks present with the same deformity. The clinician must assess the quality and quantity of available neck skin as well as the height and straightness of the cervical spine. Type I KFA consists of an extremely short skeletal neck that results in the increased width of the neck soft tissues. A spectrum of neck soft-tissue rearrangement procedures has been suggested to improve the webbed-neck deformity. Menick and colleagues modified the “butterfly” excision of redundant skin to avoid a midline scar.⁴¹ They did this by extending the more traditional inferior flaps into the scalp. Unfortunately, with this design, the scars are displaced laterally, and they become visible at the hairline, close to the original site of the web. Some surgeons feel that a midline posterior scar is often preferred aesthetically to one that can be seen along the lateral neck region. The placement of tissue expanders followed by flap rearrangements has also been carried out with some success. Thus, to review, procedures designed to correct the webbed neck suffer from an inability to elevate the hairline, noticeable scarring, and the intrinsically inadequate height of the skeletal structures of the neck.

The craniofacial skeletal deformities of patients with KFA typically present in one of two patterns.19,30,53 The first is in association with a congenital asymmetrical cervical spine fusion. In these patients, a variable degree of non-synostotic anterior plagiocephaly is present. The ipsilateral fronto–orbito–zygomatic flattening and retrusion may be significant enough that anterior cranial vault, orbital, and zygomatic reconstruction carried out through an intracranial approach will be indicated to adequately improve morphology (Fig. 31-1). These individuals will also have an asymmetrical dentofacial deformity that requires Le Fort I (maxillary) osteotomy, bilateral sagittal split ramus osteotomies of the mandible, and an osseous genioplasty procedure for three-dimensional repositioning (Fig. 31-2). The most unsettling aspect of the craniofacial reconstruction relates to the fact that the neck cannot be straightened. It will remain crooked, and so decisions about the best aesthetic positioning of the osteotomized craniofacial skeletal units must also be adjusted.

The second pattern of presentation is in association with a congenital symmetric cervical spine fusion. The cranio–orbito–zygomatic region is symmetrical and has relatively good proportions.⁵³ No reconstruction procedures are generally required in the upper facial skeleton. With reference to the maxillomandibular region, the constant open mouth posture of the mandible generally results in vertical maxillary excess and a constricted maxillary arch width. The mandible is usually retrognathic, with a vertically long retrusive chin and an open-bite malocclusion. A degree of maxillomandibular asymmetry is expected. The neck–chin angle is markedly obtuse. These individuals will benefit from orthognathic surgery in combination with orthodontic treatment. The orthognathic surgery will generally require a Le Fort I osteotomy in segments to intrude the maxilla vertically, advance it horizontally, and widen it transversely. The preferred approach also involves bilateral sagittal split ramus osteotomies of the mandible with horizontal advancement and counterclockwise rotation to match the new maxillary position in combination with a vertical reduction and advancement genioplasty (see Chapter 15).

Background

Speculation about the historic prevalence of Down syndrome has included references to depictions of the syndrome in 15th- and 16th-century paintings.69,81 Martínez-Frías described what seems to be the earliest observation of the syndrome in a sculpted terracotta head from 580 A.D.⁸⁹ The terracotta piece comes from the Toltec culture of Mexico, and its facial features, which include macroglossia, help to define its subject as a person with Down syndrome. The features of this Down syndrome were initially described by Langdon Down in 1866, and the condition represents a combination of phenotypic features that includes a degree of mental deficiency and characteristic facial features.⁷²

The birth prevalence of trisomy 21 syndrome is generally stated to be 1 in 650 live births, but it is known to vary in different populations from 1 in 600 to 1 in 2000 live births. During the 1970s, 15% of patients who had been institutionalized for mental deficiency were found to have trisomy 21 syndrome.⁷⁵

About 95% of all cases of Down syndrome arise from non-disjunction. Approximately 80% are of maternal origin, with 20% being of paternal origin. The risk increases with increasing maternal age as well as with paternal age and particularly when the parents are more than 35 years old. It has been estimated that approximately 4.8% of Down syndrome cases arise from an unbalanced translocation, which may occur de novo or by parental transmission. Inherited D/G translocations occur in 93% of maternal cases and 7% of paternal cases; however, for G/G translocations, 50% are of maternal origin, and 50% are of paternal origin. It has been estimated that 65% to 80% of trisomy 21 conceptuses result in spontaneous abortions.⁷⁵

Detectable mosaicism (found in about 3% of trisomy 21 cases) and the Down syndrome phenotype may only be partially expressed.⁷⁵ The use of the DNA samples from individuals who have partial trisomy 21 with or without features of the phenotype has been helpful for understanding the nature of the disorder. The area between loci D21S58 and D21S42 has been identified as being associated with mental retardation and with most of the facial features of Down syndrome. The facial features that have been identified in this region include oblique palpebral fissures; epicanthal folds; a flat nasal bridge; a protruding tongue; short, broad hands with clinodactyly of the fifth finger; a gap between first and second toes; hypotonia; short stature; Brushfield spots; and characteristic dermatoglyphic findings, including a single palmar crease and an increased number of ulnar loops.⁸⁸

Individuals with Down syndrome have a specific set of major congenital malformations, including heart anomalies (30% to 40%) and gastrointestinal tract anomalies such as duodenal stenosis or atresia, imperforate anus, and Hirschsprung disease.⁷⁵ The development of Alzheimer disease occurs at a much earlier age in individuals with trisomy 21 than it does in the general population. The frequency of symptomatic gallbladder disease is 25% higher among adults with Down syndrome as compared with the general population.

Down syndrome is characterized by extensive phenotypic variability.65,67,71,98 Although cognitive impairment, muscle hypotonia at birth, and dysmorphic features occur to some extent in all individuals, most associated traits occur in only a fraction of affected individuals. In the patient with Down syndrome, a number of characteristic facial features that vary from patient to patient are frequently recognized:

In 1967, Otermin Aguirre presented a series of patients with Down syndrome who underwent reconstructive surgery in an attempt to normalize their facial morphology.⁹³ During the same year, Hohler attempted to normalize the face of a young girl with Down syndrome by augmenting the hypoplastic dorsum of the nose and the receding chin with alloplastic implants.⁷⁷ In 1977, Lemperle and Spitalny systematically tried to normalize the faces of children with Down syndrome.^82–85 Similar results were published by Olbrisch,^91,92 Patterson and colleagues,⁹⁴ Wexler and Peled,^103,104 and Rozner,⁹⁹ in addition to several others.^76,90,94,97

Despite the initial enthusiasm for facial reconstruction in children with Down syndrome during the late 1960s through the mid 1980s, a critical review of the procedures used to normalize the face was not carried out until the mid to late 1980s. In 1989, Katz and Kravetz presented a balanced, thoughtful review and a discussion of the literature regarding the “effectiveness of facial surgery for persons with Down syndrome.”⁷⁹ The research of Katz and Kravetz may be summarized as follows: If improved functioning, appearance, and social acceptability are measured by parent and treating physician satisfaction, then the outcome of facial plastic surgery for people with Down syndrome seems positive. If function, appearance, and social acceptability are evaluated by people who were not involved in making the decision to conduct the facial plastic surgery—and particularly when control subjects are included in the evaluation—then the outcome of facial plastic surgery for people with Down syndrome is not so positive. For most patients with Down syndrome, the surgeons’ and parents’ well-intentioned attempts to normalize the child’s facial morphology could not be realized.⁹⁶

Macroglossia with protrusion of the large tongue is a frequent feature of Down syndrome. Dystonia or hypotonia of the tongue is also a factor.66,74 During the 1970s and the early 1980s, several investigators suggested that partial glossectomy in the patient with Down syndrome could improve the clarity of speech.^68,70 However, studies that used objective criteria to document speech results after partial glossectomy in patients with Down syndrome showed no significant differences in the number of articulation errors between audiotape recordings made preoperatively and 6 months postoperatively in a series of patients or between the recordings of the same patients and recordings of an additional series of Down syndrome control patients who did not undergo surgery. A further study by Margar-Bacal and colleagues looked at changes in the aesthetic appearance and intelligibility of speech after partial glossectomy in patients with Down syndrome.⁸⁷ The aesthetic appearance of speech (i.e., the visual acceptability of the patient while he or she is speaking) was judged from visual information only. Judgments of speech intelligibility were made separately from the auditory portion of the videotapes. The acceptability and intelligibility of the children were also judged together during audiovisual presentation. Statistical analysis showed that speech was significantly more acceptable aesthetically after surgery. No significant difference was found in speech intelligibility postoperatively as compared with preoperatively.

An Angle Class III malocclusion as a result of the midface hypoplasia with overclosure of the mandible is a frequent finding in patients with Down syndrome.⁹⁵ This was objectively studied by Farkas with the use of anthropometric measurements in which he documented that 60% of children with Down syndrome showed a disproportionately small depth to the middle third of the face (i.e., the anthropometric measurement from the subnasal point to the tragus).⁷³ The congenital absence of permanent teeth, poor root formation, and hypoplasia of the enamel are frequent complicating factors.

Author’s Approach to Facial Reconstruction in Individual’s with Down Syndrome

By the time that a individual with Down syndrome is 5 years old (with a formal speech and language assessment if the tongue is confirmed to be excessive in volume and if he or she is unable to comfortably maintain the tongue in the oral cavity), a conservative partial glossectomy may be useful to limit secondary skeletal deformities, improve breathing, and improve the aesthetic appearance of the child while he or she is eating or speaking and when his or her lower jaw is at rest. The basic procedure is a closing anterior wedge resection of the tongue that is carried out with the patient under general anesthesia. A variety of other techniques have also been described to conservatively reduce the size of the tongue.

When a child with Down syndrome approaches skeletal maturity (i.e., 14 to 16 years of age for girls, 16 to 18 years of age for boys) and a significant jaw deformity with malocclusion is present, then a comprehensive approach of orthodontic treatment and orthognathic surgery can effectively alter the facial proportions (aesthetics) and improve head and neck functions (i.e., lip posture, chewing, speech articulation, and breathing) (Fig. 31-3). A formal sleep study is indicated before surgery to clarify the extent of upper airway obstruction and the degree of maxillomandibular advancement required to manage it.^{1,78,80,86,100–102} The orthodontic treatment may be compromised as a result of poor dental root formation, congenitally missing teeth, or limited compliance. The coordination of care with an appropriate dental team (e.g., a restorative dentist, a periodontist, an orthodontist) is useful before the initiation of any treatment.

The correction of the dentofacial deformity and the management of the airway frequently requires maxillary Le Fort I osteotomy (horizontal advancement and vertical lengthening), often with sagittal split ramus osteotomies for alignment to the new maxillary position (i.e., advancement but not setback) and an osseous genioplasty (horizontal advancement and vertical lengthening). Septoplasty and inferior turbinate reduction should be simultaneously performed if required to improve nasal airflow (see Chapter 10).

Unfortunately, the numerous adnexal (eyelid) soft-tissue procedures described in the literature (e.g., lateral canthopexy) in an attempt to normalize the faces of patients with Down syndrome have mostly proven to be suboptimal.

Background

In 1849, Robert Smith, a professor of surgery at Dublin Medical School, reported clinical and necropsy findings in two cases of individuals who were presumed to have neurofibromatosis; he cited 75 references to similar patients from the earlier medical literature.¹³⁰ Unfortunately, he did not recognize that the tumors (neurofibromas) contained neural elements. In 1882, von Recklinghausen published his findings, which convinced the medical world that neurofibromatosis was a distinct entity of neural origin.¹⁶⁵ Today, neurofibromatosis is known to be etiologically heterogeneous. Cohen and Hayden were the first to differentiate Proteus syndrome from neurofibromatosis in 1979.^119,162 Types I and II are the forms that are frequently encountered by the craniomaxillofacial surgeon.

Author’s Approach to Reconstruction in Patients with Orbitotemporal Neurofibromatosis

It is recognized that the facial reconstruction of patients with this condition is often difficult as a result of the multilevel involvement of the skeleton, the soft tissues, and the viscera (i.e., brain, eyes, tongue, soft palate, sinus, and teeth). A basic premise of treatment is to preserve the seeing eye whenever feasible.114,127,135,136,155,158,159,161 The prevention of brain injury and the improvement of the tongue, lips, soft palate, and jaw function are high priorities. Jackson and colleagues have suggested a classification system for orbitotemporal neurofibromatosis that they have found useful for treatment planning¹³⁹:

It has been pointed out by Jackson and others that conservative surgical debulking procedures that leave considerable amounts of the plexiform neurofibroma leave patients prone to continued growth and the need for further surgery.¹⁴¹ Whenever feasible, more complete resection of the tumor with immediate reconstruction is preferred.

When the temporal–cheek region is extensively involved, the facial nerve presents an extra challenge. If possible, the facial nerve is dissected free, the tumor is debulked, and the soft-tissue flaps are redraped (see Fig. 31-4). When the facial nerve is extensively infiltrated by a tumor that grotesquely deforms the face, it may be necessary or preferable to resect the nerve as part of the debulking procedure. Occasionally we have used an approach that involves the radical debulking of the tumor, the planned sacrifice of the involved facial nerve, and the simultaneous reconstruction of the cheek–facial nerve defect with a reinnervated free muscle transfer.

Despite the less than ideal restoration of function and enhancement of facial aesthetics that is often achieved with the presenting orbitotemporal, temporal–cheek, and maxillomandibular neurofibromatosis deformities, patients and families are generally pleased with the efforts (see Fig. 31-4). Longitudinal computed tomography scanning and magnetic resonance imaging reassessment are useful to follow the disease process, because residual neurofibromatosis generally remains, and malignant transformation may occur.

Background

Hemihyperplasia was first described by Meckel in 1822.¹⁹² Many comprehensive reviews have been published since that time.^{173,174,181,182} In patients with hemihyperplasia, the enlarged area may run the gamut from a single digit to a single limb to unilateral facial enlargement to involvement of half of the body.^{168–170,179,183,187,189,198,199,203,206–208} In some patients, the defect is limited to a single tissue type (e.g., muscular, vascular, skeletal, nervous system).²⁰⁴

The etiology and pathogenesis of hemihyperplasia are poorly understood, with a variable range of clinical abnormalities having been described.171,175,178 This fact—in combination with the large number of reported sporadic cases—is suggestive of etiologic heterogeneity. When the face is involved, asymmetry is usually evident at birth, and it may become accentuated or at least more of a concern with age, especially at puberty.^{180,188,190,192,196,200–202} The involved bones have been found to be unilaterally enlarged, often with accelerated bone age on the affected side. A variety of non-neoplastic abnormalities of the limbs, teeth, skin, central nervous system, cardiovascular system, liver, kidneys, and genitalia have also been observed.

Various neoplasms have been reported in association with hemihyperplasia, including Wilms tumor, adrenal cortical carcinoma, and hepatoblastoma to name but a few.172,176,177,184–186,191 In the study by Hoyme and colleagues of 104 cases of isolated hemihyperplasia, tumors developed in 3.8% of patients.¹⁸⁶ The neoplasms associated with hemihyperplasia have been found to have an embryonal origin. Patients with hemihyperplasia should be screened with ultrasound for tumors every 6 months for the first 4 years of life and probably less frequently thereafter until the age of 7 years.^176,184

Any and all ipsilateral facial structures may be involved, including the bones of the cranium, the orbit, the zygoma, the maxilla, and the mandible.193–195 Premature development and eruption of the teeth occur, as does macrodontia of varying degrees. Unilateral enlargement of the tongue and its papillae is also a frequently observed feature. The overall facial soft tissues are increased in thickness, size, and volume. The eyeball and even the brain may be enlarged on the affected side.

Hemihyperplasia of the face should be distinguished from hemimandibular hyperplasia (HMH), which is a three-dimensional enlargement of the whole hemimandible but not of the other facial structures.193–195 Furthermore, in patients with HMH, no other aspects of the body are enlarged, and no predisposition to tumors has been identified. HMH was first reported by Adams in 1836.¹⁸² Epidemiologic data suggest that there is equal incidence of HMH in both sexes and in all ethnic groups. Obwegeser drew the distinction between HMH and hemimandibular elongation.^193–195 He also clearly differentiated these conditions from hemihyperplasia of the face (see Chapter 22).

Author’s Approach to Reconstruction in Patients with Hemihyperplasia

Procedures to improve facial symmetry and Euclidian proportions for the individual with hemihyperplasia of the face are offered when feasible (Fig. 31-5).¹⁹⁷ Overzealous attempts to debulk the soft-tissue enlargement (e.g., resection of the parotid gland, resection or liposuction of the deep layer soft tissues of the cheek) may result in damage to the facial nerve or introduce an “operated” look and are thus generally discouraged.²⁰⁵ Surgery should be directed at regions and tissue layers that are most amenable to safe improvement. Orthodontic treatment in combination with orthognathic surgery is often a fruitful approach. A maxillary Le Fort I osteotomy to bring the maxillary dental midline back to the facial midline; to correct canting; and to adjust the vertical dimension, horizontal projection, and arch width is frequently useful. This is combined with bilateral sagittal split ramus osteotomies of the mandible to reposition the jaw and also to recontour the inferior border. An oblique osteotomy of the chin for repositioning and also to recontour the inferior border is carried out (see Fig. 31-5).

Background

Vascular anomalies fall into two groups: hemangiomas and vascular malformations. Mulliken and Glowacki were the first to clarify a biologic classification of vascular anomalies on the basis of endothelial properties.226,231,232 Those authors described how hemangiomas have a proliferative endothelium whereas vascular malformations have a stable endothelium.²¹⁸ Hemangiomas have a natural history that is characterized by initial proliferation, stability, and then at least partial involution (Figs. 31-6 and 31-7). Vascular malformations are present at birth, although they may not be clinically evident until sometime later during childhood. In general, vascular malformations grow commensurately with the child, but they may expand suddenly as a result of trauma, infection, or hormonal influences (Figs. 31-8 through 31-11). Vascular malformations generally occur sporadically, although inherited autosomal dominant entities do exist. The International Society for the Study of Vascular Anomalies classification system is based on Mulliken and Glowacki’s work.²²⁶ Vascular tumors include hemangiomas, Kaposiform hemangioendotheliomas, tufted angiomas, pyogenic granulomas, and hemangiopericytomas. Vascular malformations include capillary, venous, lymphatic, and arteriovenous conditions; malformations can also be mixed and include combinations of these. From a clinical perspective, it is useful to think in terms of the flow characteristics of the malformations (i.e., either slow flow or fast flow) and the type of vessel drainage.^{213–215,217,223–228}

Complications from vascular malformations include venostasis, ischemia, coagulopathy, disseminated intravascular coagulopathy, heart failure, and even death.²⁰⁹ Skeletal anomalies can occur as a result of intraosseous involvement, skeletal expansion, or skeletal compression (erosion). Any head and neck function can be affected by the presence of a vascular anomaly’s tumor-like mass.

The diagnostic imaging of vascular malformations primarily relies on radiographic modalities.²¹² Phleboliths are generally pathognomonic for venous malformations. Color Doppler ultrasound is an invaluable tool for the assessment of blood flow velocities and patterns of vascular lesions. Computed tomography plays an important role in the understanding of skeletal involvement. Magnetic resonance imaging is a useful non-invasive and non-ionizing test for the accurate depiction of soft-tissue relationships and allows slow-flow malformations to be accurately differentiated from high-flow malformations. Angiography and venography can play important diagnostic and therapeutic roles in the management of specific vascular malformations. Advantages of venography include the clarification of lesion size and extent and of venous drainage patterns. Angiography can clarify arteriovenous shunting, the presence of macrofistulae and microfistulae, and the location of the lesion’s nidus. Therapeutic embolization via angiography with the use of particular materials or coils can be carried out.

Lymphatic Malformations

Lymphatic malformations are slow-flow anomalies.223,225,226,228 Macrocystic lesions are easier to deal with than microcysts. Microcystic lesions do not resolve spontaneously, and they are often harder to manage surgically as a result of their close integration within the normal head and neck soft tissues that must be preserved. Only half of lymphatic lesions are recognized at birth, but the majority are evident by approximately 2 years of age. Skeletal and soft-tissue overgrowth are typical in the craniomaxillofacial region. Cervicofacial lymphatic malformations tend to present with skeletal distortions (e.g., mandibular overgrowth, malocclusion). There may be intraosseous involvement, but skeletal expansion and erosion (remodeling) as a result of mass effect are typical. Symptoms of localized swelling, pain, and erythema associated with infection are common. Significant complications include intralesional bleeding and infection that are often associated with rapid expansion and then moderate regression. Rapid swelling can lead to airway obstruction. Macrocysts may undergo involution if they are ruptured by trauma, or they may be treated via the injection of sclerosing agents or aspiration. However, surgical removal should be considered, when feasible. Complete resection is seldom possible because lymphatic malformations often surround and incorporate normal anatomy that is not deemed appropriate for resection (see Figs. 31-8 and 31-9).^{220–222,229,230} Orthognathic procedures would frequently be beneficial but are not often carried out.

Venous Malformations

Venous malformations are the most common form seen in the head and neck region.223,225,226,228 They are present at the time of birth, but they may not have been recognized, or they may have been misdiagnosed.^210,219 Histologically, they are composed of variably sized, thickened, dilated, spongy channels that are devoid of smooth muscle and lined by endothelial cells. Clinically, they are compressible subcutaneous masses that are often deep blue in color. They generally grow commensurate with the child but, as with lymphatic malformations, trauma, infection, and hormonal changes can cause rapid expansion. Venous malformations can involve any tissue layer (i.e., skin, mucosa, muscle, brain, bone, or viscera). Thrombosis within the malformation commonly leads to phlebolith formation. When present, phleboliths are pathognomonic and assist with the accurate diagnosis. Venous malformations are usually unilateral and result in significant facial asymmetry and dysfunction. They may affect speech, swallowing, chewing, breathing, vision, hearing, cognition, and jaw or neck range of motion. They may be intraosseous or have secondary effects on the bone (i.e., expansion, remodeling, or resorption). Treatment to reduce the size of venous malformations includes the injection of sclerosing agents in an attempt to damage the endothelial cells via intravascular thrombosis and fibrosis as well as partial surgical excision (see Figs. 31-8, 31-9, and 31-10).^{220,221,222,229}

Arteriovenous Malformations

Arteriovenous malformations are high-flow malformations with a direct connection between an artery and a vein, with no intervening capillary bed.223,225,226,228 These malformations are also present at birth, but they may have gone unrecognized or have been misdiagnosed as a more straightforward hemangioma. The confirmation of clinical diagnosis is helpful with color Doppler examination, which can determine flow rate, volume, and reversal of flow. Magnetic resonance imaging can determine the extent of the lesion and its relationship with the surrounding anatomy. Angiography can further clarify the lesion and be used for the therapeutic embolization of an arteriovenous malformations. If an arteriovenous malformation is well localized and can be reliably excised with satisfactory reconstruction, this is always a first choice (see Fig. 31-11). Unfortunately, larger, more extensive lesions are not surgically resectable. Superselective embolization performed by an experienced interventional radiologist with the placement of an ablative agent (e.g., absolute alcohol, sodium tetradecyl sulfate) to induce the destruction of the endothelium may be useful. Embolization that involves coils or particles is another technique for temporarily occluding flow. The ligation of feeding vessels or proximal embolization is generally avoided, because rapid collateralization tends to occur.^{220,221,222,229}

Capillary Malformations

Capillary malformations, which were previously referred to as port-wine stains, are intradermal vascular anomalies.223,225,226,228 They occur in less than 1% of newborns, and they have an equal distribution in male and female individuals.²¹⁶ They typically present as either pink or red cutaneous discolorations. They have a tendency to darken, thicken, and become nodular with age. Several conditions are associated with capillary malformations, including Sturge–Weber syndrome, which presents with capillary malformations in the trigeminal nerve distribution in combination with vascular anomalies of the leptomeninges, often with a seizure disorder, developmental delay, and eye involvement (i.e., glaucoma and retinal detachment).²¹¹ Proteus syndrome may also be associated with cutaneous vascular malformations.²¹⁵ When feasible, the treatment of capillary malformations with a pulsed dye laser should be considered.

Background

Velocardiofacial syndrome (VCFS) is a genetic condition that is characterized by abnormal pharyngeal arch development that results in defective development of the thymus, the parathyroid glands, and the conotruncal region of the heart. Shprintzen and colleagues first described this syndrome in1978.²⁴⁹ Since then, almost 200 different individual clinical features have been associated with VCFS.^233,240,247 No single individual has been found to have all of the described features. Affected individuals will present with unique facial features, and they may also have cardiac defects, palatal abnormalities, hypernasal speech, hypotonia, defective thymic development, and a variety of learning disabilities.²⁴⁸

Approximately 75% of individuals with VCFS have cardiac anomalies. The cardiac defects are usually of the conotruncal type.234,242 The most common variations include an interrupted aortic arch (50%), truncus arteriosus (35%), and tetralogy of Fallot (16%). Palatal abnormalities predispose these individuals to speech difficulties. Defective thymic development is associated with impaired immune function. Learning disabilities include overt developmental delay, psychiatric disorders, and musculoskeletal defects.²³⁸ Interestingly, ophthalmologic abnormalities occur in approximately 70% of individuals with VCFS; these may include bilateral cataracts, tortuous retinal vessels, and small optic discs.

Approximately 10% of individuals with VCFS will have DiGeorge syndrome, which consists of at least two of the three following features²³⁹:

Approximately 15% to 20% of patients with VCFS will be born with Pierre Robin sequence (see Chapter 4). Many individuals are mistakenly categorized as having CHARGE syndrome.

Pathophysiology

VCFS is now known to be a congenital disorder that is caused by a microdeletion at the Q11.2 band, which is located on the long arm (Q) of chromosome 22.235,243 The microdeletion is known to cause an abnormality of morphogenesis that affects the migration of the neural crest cells and therefore the early development of branchial arches. In approximately 90% of affected individuals, the disorder occurs as a result of a new mutation. In the other 10% of cases, the disorder is inherited from a parent in an autosomal dominant fashion. Affected individuals have a 50% chance of passing VCSF to each offspring.²⁴⁴

Epidemiology

The prevalence of VCFS is the United States is approximately 1 in 2000 live births. Internationally, the syndrome occurs in 1 in 4000 live births. The frequency of VCFS in newborns with isolated cleft palate is approximately 8%. There seems to be no gender predilection. The syndrome is present at birth, but it is often unrecognized until childhood or later.²³⁷ Although the heart defect or the cleft palate is generally detected soon after birth, the learning disorders and psychiatric illnesses may not become apparent until the school-aged years.²³⁶ Even then the correct diagnosis is not always made.

DiGeorge syndrome, which involves a total absence of the thymus and a severe T-cell immunodeficiency, is found in less than 0.5% of patients with VCFS.236,241,245 Most affected individuals have only partial defects, with impaired thymic development and variable defects in their T-cell numbers.

Author’s Approach to Reconstruction in Patients with Velocardiofacial Syndrome

Evaluation by clinicians who have experience with clefting usually centers around the issue of hypernasal speech and whether or not a palatal procedure is indicated. Concern about the location of the carotid arteries (when considering the use of a pharyngeal flap) is always part of the discussion.²⁴⁶

A percentage of teenagers with VCFS will present with a jaw deformity and malocclusion. These patients will benefit from a comprehensive orthodontic and surgical approach. They generally have a long face growth pattern (see Chapter 21) and require osteotomies of the maxilla, the mandible, and the chin region (Fig. 31-12).

Klippel–Feil Anomaly

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Down Syndrome

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Neurofibromatosis

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Hemihypertrophy of the Face

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176. Fraumeni, JF, Jr., Geiser, CF, Manning, MD. Wilms’ tumor and congenital hemihypertrophy: Report of five new cases and review of literature. Pediatrics. 1967; 40:886.

177. Fraumeni, JF, Miller, RW. Adrenocortical neoplasms with hemihypertrophy, brain tumors, and other disorders. J Pediatr. 1967; 70:129.

178. Furnas, DW, Soper, RT, Nickman, NJ, et al. Congenital hemihypertrophy of the face: Impersonator of childhood facial tumors. J Pediatr Surg. 1970; 5:344.

179. Gesell, A. Hemihypertrophy and twinning: Further study of the nature of hemihypertrophy with report of a new case. Am J Med Sci. 1927; 173:542.

180. Gonzalez-Crussi, F, Lee, SC, McKinney, M. The pathology of congenital localized gigantism. Plast Reconstr Surg. 1977; 59:411.

181. Gorlin, RJ, Cohen, MM, Jr., Levin, LS. Syndromes of the head and neck, ed 3. New York: Oxford University Press; 1990.

182. Gorlin, RJ, Meskin, LH. Congenital hemihypertrophy. J Pediatr. 1962; 61:870.

183. Haicken, BN. Congenital hemihypertrophy. Am J Dis Child. 1970; 120:373.

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185. Hennessy, WT, Cromie, WJ, Duckett, JW. Congenital hemihypertrophy and associated abdominal lesions. Urology. 1981; 18:576.

186. Hoyme HE, et al: The incidence of neoplasia in children with isolated congenital hemihypertrophy. David Smith Meeting on Malformations and Morphogenesis, Burlington, Vt, August 11–14, 1986.

187. Khanna, JN, Andrade, NN. Hemifacial hypertrophy: Report of two cases. Int J Oral Maxillofac Surg. 1989; 18:294.

188. Kogon, SL, Jarvis, AM, Daley, TD, et al. Hemifacial hypertrophy affecting the maxillary dentition. Oral Surg Oral Med Oral Pathol. 1984; 58:549.

189. Lenstrup, E. Eight cases of hemihypertrophy. Acta Pediatr Scand. 1926; 6:205.

190. Loh, HS. Congenital hemifacial hypertrophy. Br Dent J. 1982; 153:111.

191. Meadows, AT. Wilms’ tumor in three children of a woman with hemihypertrophy. N Engl J Med. 1974; 291:23.

192. Meckel, JF. Uber die seitliche asymmetrie im tierichen korper, anatomische physiologische beobachtungen und untersuchungen. Renger: Haile; 1822.

193. Obwegeser, HL. Descriptive terminology for jaw anomalies. Oral Surg Oral Med Oral Pathol. 1993; 75:138–140.

194. Obwegeser, HL. Mandibular growth anomalies: Terminology-aetiology-diagnosis-treatment. Berlin, Heidelberg, NY: Springer-Verlag; 2001.

195. Obwegeser, HL, Mekek, M. Hemimandibular hyperplasia—hemimandibular elongation. J Maxillofac Surg. 1986; 14:183–208.

196. Pollock, RA, Newman, MH, Burdi, AR, et al. Congenital hemifacial hyperplasia: An embryologic hypothesis and case report. Cleft Palate J. 1985; 22:173.

197. Posnick, JC. Other craniofacial syndromes: Klippel–Feil anomaly, neurofibromatosis, Down syndrome, micro-ophthalmia, hemifacial hyperplasia (hemi-hypertrophy). In: Posnick JC, ed. Craniofacial and maxillofacial surgery in children and young adults. Philadelphia: WB Saunders Co; 2000:503–527.

198. Reed, EA. Congenital total hemihypertrophy. Arch Neurol Psychiatry. 1925; 14:824.

199. Ringrose, RE, Jabbour, JT, Keele, DK. Hemihypertrophy. Pediatrics. 1965; 36:434.

200. Rudolph, DC, Norvold, RW. Congenital partial hemihypertrophy involving marked malocclusions. J Dent Res. 1944; 23:133.

201. Sculerati, N, Jacobs, JB. Congenital facial hemihypertrophy: Report of a case with airway compromise. Head Neck Surg. 1985; 8:124.

202. Spielman, WR, Marano, PD, Kolodny, SC, et al. True hemifacial hypertrophy: Report of case. J Oral Surg. 1971; 29:592.

203. Tommasi, AF, Jitomirski, F. Crossed congenital hemifacial hemihyperplasia. Oral Surg Oral Med Oral Pathol. 1989; 67:190.

204. Viljoen, D, Pearn, J, Beighton, P. Manifestations and natural history of idiopathic hemihypertrophy: A review of eleven cases. Clin Genet. 1984; 26:81.

205. Viteporn, S. Surgical-orthodontic treatment in hemifacial hypertrophy: A case report. Int J Adult Orthodon Orthognath Surg. 1993; 8:55.

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Vascular Malformations

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210. Berenguer, B, Burrows, PE, Zurakowski, D, et al. Sclerotherapy of craniofacial venous malformations: Complications and results. Plast Reconstr Surg. 1999; 104:1.

211. Burns, AJ, Kaplan, LC, Mulliken, JB. Is there association between hemangioma and syndromes with dysmorphic features? Pediatrics. 1991; 88:1257–1267.

212. Burrows, PE, Mulliken, JB, Fellows, KE, et al. Childhood hemangiomas and vascular malformations: Angiographic differentiation. AJR Am J Roentgenol. 1983; 141:483.

213. Cohen, MM, Jr. Vasculogenesis, angiogenesis, hemangiomas, and vascular malformations. Am J Med Genet. 2002; 108:265–274.

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215. Cohen, MM, Jr., Neri, G, Weksberg, R. Overgrowth syndromes. New York: Oxford University Press; 2002.

216. Enjolras, O, Mulliken, JB. The current management of vascular birthmarks. Pediatr Dermatol. 1993; 10:311.

217. Enjolras, O, Mulliken, JB. Vascular tumors and vascular malformations. Adv Dermatol. 1998; 13:375–423.

218. Folkman, J, D’Amore, PA. Blood vessel formation: What is its molecular basis? Cell. 1996; 87:1153.

219. Hein, KD, Mulliken, JB, Kozakewich, HPW, et al. Venous malformations of skeletal muscle. Plast Reconstr Surg. 2002; 110:1625.

220. Jackson, IT, Carreno, R, Potparic, Z, et al. Hemangiomas, vascular malformations, and lymphovenous malformations: Classification and methods of treatment. Plast Reconstr Surg. 1993; 91:1216.

221. Jackson, IT, Keskin, M, Yavuzer, R, et al. Compartmentalization of massive vascular malformations. Plast Reconstr Surg. 2005; 115:10.

222. Marler, JJ, Mulliken, JB. Current management of hemangiomas and vascular malformations. Clin Plast Surg. 2005; 32:99.

223. Mulliken, JB. Cutaneous vascular anomalies. Semin Vasc Surg. 1993; 6:204–218.

224. Mulliken, JB. Vascular anomalies. In: Aston SJ, Beasley RW, Thorne CHM, eds. Grabb and Smith’s plastic surgery. ed 5. Philadelphia: Lippincott-Raven; 1997:191.

225. Mulliken, JB, Fishman, SJ, Burrows, PE. Vascular anomalies. Curr Probl Surg. 2000; 37:517.

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227. Mulliken, JB, Murray, JE, Castaneda, AR, et al. Management of a vascular malformation of the face using total circulatory arrest. Surg Gynecol Obstet. 1978; 146:168.

228. Mulliken, JB, Young, AE. Vascular birthmarks: Hemangiomas and malformations. Philadelphia: Saunders; 1998.

229. Posnick, JC. Hemangiomas and vascular malformations of the head and neck: Evaluation and management. In: Posnick JC, ed. Craniofacial and maxillofacial surgery in children and young adults. Philadelphia: WB Saunders Co; 2000:564–596.

230. Pribaz, JJ, Morris, DJ, Mulliken, JB. Three-dimensional folded free-flap reconstruction of complex facial defects using intraoperative modelling. Plast Reconstr Surg. 1994; 93:285.

231. Takahashi, K, Mulliken, JB, Kozakewich, HPW, et al. Cellular markers that distinguish the phases of hemangioma during infancy and childhood. J Clin Invest. 1994; 93:2357.

232. Vikkula, M, Boon, LM, Mulliken, JB. Molecular genetics of vascular malformations. Matrix Biol. 2001; 20:327.

Velocardiofacial Syndrome

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234. Carotti, A, Digilio, MC, Piacentini, G, et al. Cardiac defects and results of cardiac surgery in 22q11. 2 deletion syndrome. Dev Disabil Res Rev. 2008; 14:35–42.

235. Cuneo, BF. 22q11. 2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. Curr Opin Pediatr. 2001; 13:465–472.

236. De Smedt, B, Swillen, A, Ghesquiere, P, et al. Pre-academic and early academic achievement in children with velocardiofacial syndrome (del22q11. 2) of borderline or normal intelligence. Genet Couns. 2003; 14:15–29.

237. Digilio, MC, Angioni, A, De Santis, M, et al. Spectrum of clinical variability in familial deletion 22q11. 2: from full manifestation to extremely mild clinical anomalies. Clin Genet. 2003; 63:308–313.

238. Dyce, O, McDonald-McGinn, D, Kirschner, RE, et al. Otolaryngologic manifestations of the 22q11. 2 deletion syndrome. Arch Otolaryngol Head Neck Surg. 2002; 128:1408–1412.

239. Eberle, P, Berger, C, Junge, S, et al. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11. 2 microdeletion and partial DiGeorge syndrome. Clin Exp Immunol. 2009; 155:189–198.

240. Goldberg, R, Motzkin, B, Marion, R, et al. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. 1993; 45:313–319.

241. Goldmuntz, E. DiGeorge syndrome: new insights. Clin Perinatol. 2005; 32:963–978.

242. Goldmuntz, E, Clark, BJ, Mitchell, LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. 1998; 32:492–498.

243. Kelly, D, Goldberg, R, Wilson, D, et al. Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11. Am J Med Genet. 1993; 45:308–312.

244. McDonald-McGinn, DM, Zackai, EH. Genetic counseling for the 22q11. 2 deletion. Dev Disabil Res Rev. 2008; 14:69–74.

245. McLean-Tooke, A, Spickett, GP, Gennery, AR. Immunodeficiency and autoimmunity in 22q11. 2 deletion syndrome. Scand J Immunol. 2007; 66:1–7.

246. Mehendale, FV, Sommerlad, BC. Surgical significance of abnormal internal carotid arteries in velocardiofacial syndrome in 43 consecutive hynes pharyngoplasties. Cleft Palate Craniofac J. 2004; 41:368–674.

247. Ryan, AK, Goodship, JA, Wilson, DL, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997; 34:798–804.

248. Shprintzen, RJ. Velo-cardio-facial syndrome: 30 years of study. Dev Disabil Res Rev. 2008; 14:3–10.

249. Shprintzen, RJ, Goldberg, RB, Lewin, ML, et al. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. 1978; 15:56–62.