Andrew L. Sonis and Brian Grove
While dental caries and its consequences represent the most common oral pathology encountered in children, both localized and systemic conditions of noncariogenic origin may manifest themselves in the mouth and surrounding tissues. This chapter will review some of the common and uncommon pathologies observed in or around the oral cavity of children.
SOFT TISSUE PATHOLOGY
ANGIONEUROTIC EDEMA
Angioneurotic edema is an allergic reaction often involving the oral soft tissues (see Chapter 189). Antigens precipitating this reaction include food and latex allergies, vaccines, insect bites, and medications. Typically, facial edema follows exposure to the antigen and may include swelling of intraoral soft tissues, potentially resulting in airway embarrassment. Initial management is provided with antihistamines. More aggressive therapy may require the administration of corticosteroids.1–10
ANKYLOGLOSSIA
Ankyloglossia (tongue-tie; Fig. 378-1) is a congenital anomaly of the tongue characterized by a short and sometimes anteriorly inserted frenulum. The clinical significance of ankyloglossia is a matter of controversy, particularly as it relates to breastfeeding difficulties such as sore nipples, poor infant weight gain, neonatal dehydration, and shortened breastfeeding duration. Infants with ankyloglossia and associated problems with latching may benefit from frenectomy. Rarely in the older child will it interfere with speech or contribute periodontal problems. Recent studies suggest some advantage of laser frenectomy over traditional surgical frenectomy relative to pain and recovery times.11–13
FIGURE 378-1. Ankyloglossia (tongue tied). A short lingual frenum may interfere with feeding or speech and may necessitate surgical intervention.
BACTERIAL INFECTIONS
Dental caries is the most common bacterial infection in the mouth that may progress to abscess and cellulitis if left untreated. (The caries process is described in Chapter 374). Non-tooth-related intraoral bacterial infections are relatively uncommon. Extraoral bacterial infections tend to be far more common (see Chapter 367). Several other systemic conditions that have bacterial etiologies can present with oral lesions. These include streptococcal infections (see Chapter 285), diphtheria, tuberculosis, cat-scratch disease, actinomycosis, gonorrhea, and syphilis.
BITE INJURIES
Accidental self-inflicted bite injuries are quite common in children, especially after having received intraoral local anesthesia. Not infrequently, children who have received a mandibular nerve block for dental treatment will chew their lip, buccal mucosa, or inner lip unknowingly, resulting in a significant area of epithelial necrosis accompanied by edema. Sites most frequently involved are the lateral border and tip of the tongue, buccal mucosa, and lower lip. The injury usually presents as a macerated, irregular lesion with painless white necrotic areas of epithelium surrounding the ulcerated surface. Treatment, if necessary, is supportive and palliative since these areas of trauma rarely, if ever, become secondarily infected.17
FIGURE 378-2. Cheilitis. The habit of chronic lip-licking can result in significant inflammation of the perioral tissues. Severe cases typically respond well to topical steroids.
CHEILITIS
Cheilitis (Fig. 378-2) is a common inflammatory disorder in children. It typically arises from the chronic habit of licking the lips and perioral skin. Less frequently, cheilitis or angular cheilosis (perlèche) may occur from mechanical irritation, malocclusion, atopic dermatitis, fungal infection (typically candidiasis), bacterial infection, or nutritional deficiencies. The clinical features of cheilitis are erythema, mild edema, and thin scaling formation of the lips and perioral areas. When due to chronic lip-licking, treatment should be directed at breaking the habit. Empirically, this may be accomplished with lip balms with undesirable tastes. In severe cases, topical steroids, with or without fungicidal and bactericidal activity, may be beneficial. Obviously, in cases where a nutritional deficiency is thought to be the underlying etiology, nutritional supplements are indicated.18-20
CONGENITAL EPULIS
Congenital epulis (Fig. 378-3) or gingival granular cell tumor of the newborn is a relatively rare lesion typically arising from the maxillary anterior alveolus. Far more common in females (8:1), it presents as a smooth, firm, pedunculated soft-tissue lesion attached to the alveolus by a broad base. It can range in size from several millimeters to several centimeters, with larger lesions frequently being detected in utero.
ERUPTION HEMATOMA
An eruption hematoma (Fig. 378-4) is a soft tissue variant of the dentigerous cyst that develops around the crown of an erupting primary or permanent tooth. It is quite common and can occur in association with any erupting tooth. The lesion typically resolves on its own with the eruption of the underlying tooth. Rarely is it necessary to excise the roof of the cyst to allow for eruption of the involved root.
FIBROMA
The irritation fibroma is considered the most common childhood reactive lesion of the oral cavity. In the vast majority of cases, the lesion arises as a reaction to a local irritant. While the lesion may involve any oral anatomic site, the buccal mucosa and interdental gingiva are the most common sites in children. The lesion usually presents as an asymptomatic pedunculated or sessile growth secondary to irritation. Treatment is surgical excision with the elimination of any associated source of local irritation.22,23 Failure to remove the source of irritation will likely result in recurrence.
FIGURE 378-3. Congenital epulis. These benign neoplasms typically arise from the anterior maxilla and can range in size from several millimeters to centimeters. Excision of smaller lesions not interfering with function may be deferred several months to minimize anesthetic risk.
CANDIDIASIS
Candidiasis or candidosis is an infection with the yeastlike fungal organism Candida, the most common being Candida albicans. It often infects children and adults who are immunocompromised or who are on a prolonged course of antibiotic therapy. It is the most common oral fungal infection in humans and can be manifest in a variety of clinical presentations, which may make appropriate diagnosis difficult.24
Erythematous, or chronic atrophic candidiasis, may also be caused by immunosuppression, xerostomia, or chronic exposure to broad-spectrum antibiotic therapy. Patients often complain of a burning sensation on their tongue associated with a loss of filiform papilla and a denuded appearance of the tongue’s dorsal surface. Unlike the acute form characterized by sloughing white lesions, the erythematous form results in patchy lesions. Many forms of chronic candidiasis are asymptomatic, including central papillary atrophy and median rhomboid glossitis. In addition, angular cheilitis is a particular form of erythematous candidiasis that affects the commissures and is characterized by fissuring, erythema, and scalelike lesions. The treatment regimen is similar to that of acute candidiasis.24–27
FIGURE 378-4. Eruption hematoma. Often associated with an erupting primary tooth, these benign lesions are the result of hemorrhage into the cystic cavity surrounding the crown of the involved tooth.
Pseudomembranous candidiasis (acute) is the most common form of oral candidiasis, which is usually seen on the buccal mucosa, dorsum of the tongue, and soft-palate (eFig. 378.1 ). It is commonly known as thrush and appears as white cottage cheese–like lesions that can be removed by scraping. It is the most common manifestation of HIV infection in children. Topical antifungal medications are often the drug of choice for localized candidiasis. While compliance for the “swish and swallow” routine with these medications is readily accomplished by older patients, in the infected infant, appropriate delivery of the topical medication is often problematic. A foam-headed device (Toothette) is a useful aid in applying the medication to the infected oral mucosa. Pharmacotherapy includes Nystatin oral suspension, Clotrimazole troche, or systemic antifungal mediations such as ketoconazole or fluconazole.24–27
GEOGRAPHIC TONGUE (ERYTHEMA MIGRANS)
Geographic tongue (Fig. 378-5) is a harmless common disorder of unknown etiology that primarily affects the dorsal surface of the tongue, although it may occasionally involve other mucosal surfaces, including the buccal and sublingual mucosa. The involved area typically changes or “migrates” over several weeks or months, thus giving rise to the disorder’s name. Onset tends to be fairly rapid, with lesions typically persisting for several weeks, although occasionally they may last for several years. Patients are generally asymptomatic but may rarely complain of a “burning” sensation. No treatment is necessary; however, patients experiencing burning may benefit from palliative treatment with topical anesthetics.28
FIGURE 378-5. Geographic tongue (erythema migrans). Commonly appearing on the dorsal surface of the tongue, the lesion is characterized by localized atrophy of the filiform papillae. Less commonly, other oral mucosal surfaces may be involved.
HAIRY TONGUE
An accumulation of keratin and elongation and hypertrophy of the filiform papillae of the tongue results in the clinical appearance of hairy tongue. While the etiology is unknown, it is correlated with several predisposing factors, including poor oral hygiene, mouthrinses containing sodium perborate, long-term antibiotics, steroid therapy, head and neck irradiation, and C albicans. Clinically, the elongated filiform papillae can range in color from white to brown to black. Although patients are typically asymptomatic, they may occasionally complain of a bad taste or halitosis. Treatment involves removing the precipitating factors and improved oral hygiene, including brushing the tongue. A unique form of hairy tongue is associated with HIV and is referred to as hairy leukoplakia. While this condition is usually observed in adults with HIV, there have been several reports of its occurrence in HIV-infected children. The lateral border of the tongue is most commonly affected bilaterally and is thought to be associated with Epstein-Barr virus infection.29-31
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
Melanotic neuroectodermal tumor of infancy is a rare condition that could potentially be confused with the congenital epulis. Similarities to the congenital epulis include its appearance in infancy (most common age being 1 to 3 months), it being more common in females (3:2), and it most commonly involving the anterior maxilla. However, unlike congenital epulis, the melanotic tumor of infancy is a locally aggressive lesion capable of causing significant tissue damage. It is believed the tumor arises from neural crest. The most common manifestation of the tumor is a soft tissue mass with an intact mucosal surface. The lesion may contain blue or black areas of pigmentation and may grow large enough to obliterate the labial buccal vestibule with resultant displacement and elevation of the lip. Pain is rarely associated with this tumor, whose growth rate is variable. Surgical excision or enucleation is the recommended treatment. Recurrence is relatively common, with rates as high as 20%.32
MUCOCELE
Mucoceles (Fig. 378-6) are the most common salivary gland problem of childhood. They typically arise in the mucosa of the lower lip as a result of trauma to a minor salivary gland, although they may occur less frequently on the buccal mucosa, soft palate, or upper lip. The extravasation of saliva into the surrounding soft tissue causes the formation of a pseudocyst. This lesion clinically appears as a painless, raised, dome-shaped lesion and may be clear, pink to red, or bluish in color, or it may be pale and fibrotic. Size is typically less than a centimeter in diameter. A common sign is a periodic reduction in swelling due to rupture and partial release of fluid, followed by recurrence due to new accumulations of fluid. While mucoceles will occasionally resolve spontaneously, most require surgical excision.33
NEONATAL CYSTS
Neonatal cysts (Fig. 378-7) are benign developmental lesions. Previously, they were differentiated based upon locations. Epstein’s pearls are remnants of epithelial tissue trapped during the palatal fusion that occurs during the 8th to 10th gestational week. Bohn’s nodules are remnants of mucous gland tissue found on the buccal or lingual aspects of the dental ridges. Dental lamina cysts are found along the crest of the ridges.1,4,8 These terms, however, are frequently confused and used synonymously. Currently, the terms palatal cysts (designating epithelial cells that persist at the site of fusion of the palatal shelves) and alveolar cysts (remnants of degenerating dental lamina on the buccal, lingual, or crest portion of the alveolar ridge), are used in descriptions to avoid confusion.4 Alveolar cysts have also been referred to as “gingival cysts” or “inclusion cysts” in some texts. The clinical description of palatal and alveolar cysts varies in color from white, to gray, to yellow nodules, in size from a pinhead to 3 mm, and in numbers from 1 to 6. The frequency of inclusion cysts is high in newborns, but they are rarely seen after 3 months of age. The prevalence in term infants varies from 65% to 85% for palatal cysts and depending on location, 9% for mandibular alveolar cysts to 36% for maxillary alveolar cysts. Prevalence is lower in premature infants.34 White infants are more likely to have palatal and alveolar cysts than African-American infants. No gender difference has been reported.
FIGURE 378-6. Mucocele. Trauma to the lower lip may result in occlusion of a minor salivary gland duct with extravasation of saliva into the surrounding soft tissue. Mucoceles are typically treated with surgical excision.
FIGURE 378-7. Neonatal cysts. These painless cysts are extremely common findings in infants. There are three forms: Bohn’s nodules (seen here), which typically present as multiple lesions on the buccal and lingual aspects of the alveolus; dental lamina cysts, which appear on the crest of the alveolus; and Epstein’s pearls, which present on the midline of the palate. None require any intervention and resolve spontaneously.
No treatment is necessary.35
OBSTRUCTIVE SIALADENITIS
Obstructive sialadenitis occurs as the result of a sialolith or foreign body blocking the normal flow of saliva, most commonly from the submandibular gland. Patients often complain of a painful swelling related to meals. The swelling generally dissipates over several hours. Symptoms may include pain, erythema of the overlying skin, fever, and an elevated white blood cell count. Treatment includes antibiotics, salivary flow stimulation, and heat. Surgery may be indicated to remove the sialolith and to establish patency of the duct. In recurrent cases, excision of the submandibular gland may be necessary.36
PYOGENIC GRANULOMA
The pyogenic granuloma is a relatively common benign vascular lesion of the skin and mucosa that arises from an exaggerated tissue response to local irritation. Typically found on the gingiva in the the oral cavity, it can be found on the tongue, lips, and buccal mucosa. The granuloma appears as a painless, nodular, erythematous mass that is typically either pedunculated or sessile. The color ranges from bluish to purple and may resemble a hemangioma. The surface may be smooth or lobulated and is frequently ulcerated and covered with a whitish-yellow pseudomembrane. Probing or palpating this soft lesion will frequently result in bleeding. It grows rapidly and ranges in size from 5 to 10 mm. Since these lesions arise from an excessive tissue response to a local irritant, treatment involves both surgical excision and removal of the source of irritation. When on the gingiva, the irritant is typically calcified plaque (calculus), which must be removed from the tooth surface to prevent recurrence.37
RANULA
A ranula is a form of mucous-retention cyst that occurs on the floor of the mouth in association with the sublingual gland or, less frequently, the submandibular gland. While they may be congenital, most arise from trauma. The ranula presents as a smooth, dome-shaped, painless, fluctuant swelling. The color is typically bluish, but deep lesions may appear as normal mucosa. Smaller ranulas are typically excised, while larger lesions may require marsupialization.38-40
RECURRENT APHTHOUS STOMATITIS
Recurrent aphthae, or canker sores, are the most common forms of oral ulcerations in both children and adults. Epidemiological studies indicate that the prevalence of recurrent aphthous stomatitis (ARS) in the general population is between 2% and 50%, with onset typically occurring in childhood. These episodic ulcerations generally continue past childhood and adolescence and occur throughout the patient’s life span, with no age, sex, race, or geographic-related predilection.
There are three forms of the disorder: minor, major (Sutton’s disease), and herpeti-form. Minor aphthae are typically round, small (less than 10 mm in diameter), well-circumscribed ulcerations surrounded by an erythematous halo. These usually occur on movable or unbound (nonkeratinized) mucosa. Several may be present simultaneously. Healing is spontaneous within 7 to 10 days, usually without scarring.
Major aphthae are similar but are larger in size (greater than 1 cm in diameter), are generally much deeper, and may be debilitating. Healing may take 10 to 30 days and may result in scarring.
Herpetiform ulcers are very small (1 mm in diameter) and often occur in clusters. There is a tendency for adjacent ulcers to coalesce and form a larger affected area. Healing takes place usually within 7 to 10 days. The name results from the clinical manifestation resembling a recurrent intraoral herpetic infection. All three clinical types are associated with varying degrees of pain and discomfort, the extent of which depends on the location, size, and depth of the ulcers. The etiology of recurrent aphthous stomatitis is unknown, although an altered local immune response is the suspect. Precipitating factors include stress, endocrine alterations, allergies, trauma, and food hyper-sensitivity. Patients with frequent recurrences should be screened for potential underlying diseases such as anemia, nutritional deficiencies (eg, iron, folate, vitamin B12), diabetes mellitus, immunosuppression, and inflammatory bowel disease (Table 378-1). Treatment is primarily aimed at pain relief and accelerating the healing process. All therapies are palliative, and none have resulted in permanent remission.
VIRAL INFECTIONS
A variety of viral infections manifest with oral lesions. Condyloma acuminatum is a benign papillary lesion most commonly associated with human papillomavirus (HPV) 16 and 18 and is usually sexually transmitted (see Chapter 233). Squamous papilloma is also an HPV infection that can result in numerous exophytic white or pink fingerlike projections that resemble cauliflower or warts. The oral lesions are most commonly seen on the lips and on the palate, uvula, and dorsum of the tongue. They are transmitted through direct contact, and the only definitive treatment is excision, cryotherapy, or electrosurgery. Recurrence is rare.49,54
Epstein-Barr virus (EBV) causes several diseases that may have oral or maxillofacial manifestations, such as infectious mononucleosis, hairy leukoplakia, Burkitt’s lymphoma, and nasopharyngeal carcinoma (see Chapter 311). Enteroviruses, particularly Coxsackie virus are associated with febrile illnesses with oral vesicular lesions that may progress to an ulcer appearance (see Chapter 306 and Fig. 306-3). HIV infection predisposes an infected child to a myriad of characteristic oral lesions and manifestations, including candida, parotid enlargement, angular cheilitis, herpetic stomatitis, oral hairy leukoplakia, petechiae, aphthous stomatitis, linear gingival erythema, and cervical lymphadenopathy (see Chapter 315). Herpes simplex virus type 1 (HSV-1) causes both primary and recurrent herpetic gingivostomatitisthat is characterized by vesicular lesions on the gingival tissue, lips, tongue, buccal mucosa, and soft palate. These lesions will often appear in clusters and may frequently coalesce, creating large areas of painful ulcerations that resemble aphthous ulcerations (see Chapter 309 and Fig. 309-1). Intraoral lesions of measles (Koplik spots) are present prior to the rash on the skin and appear on day 2 or 3 (see Chapter 316 and Fig. 316-2). A more detailed discussion of each of these entities is provided in the referenced chapters and on the DVD.
Table 378-1. Differential Diagnosis of Intraoral Ulcers
HARD TISSUE PATHOLOGY
Intraoral hard tissue pathologies refer to conditions afflicting the skeletal components of the masticatory system, namely the maxilla, mandible, and alveolar bone, or the dentition. Both the skeletal conditions and anomalies of tooth number, size, shape, and color may manifest as isolated occurrences or may reflect an underlying systemic disturbance.
AGGRESSIVE AND MALIGNANT NEOPLASMS OF THE JAWS
Aggressive and malignant jaw neoplasms and tumors are rare in children. These include the melanotic neuroectodermal tumor of infancy (described elsewhere), Langerhans cell histiocytosis, Ewing’s sarcoma, primitive neuroectodermal tumor, osteosarcoma, and desmoplastic fibroma of bone.
Approximately 10% of Langerhans cell histiocytosis cases have oral involvement. Localized destruction of the tooth-supporting bone frequently results in mobile teeth, usually in the mandible.81,82 Typically, these hard tissue lesions are accompanied by soft tissue involvement characterized by localized ulceration and necrosis.
Ewing’s sarcoma and primitive neuroectodermal tumors involve the jaws in fewer than 3% of the cases. Typical symptoms are jaw enlargement frequently accompanied by pain.
Approximately 6% to 7% of all osteogenic sarcomas occur in the maxillofacial region. The most common clinical manifestations of osteosarcoma of the jaws is rapid enlargement of the affected bone that may or may not be accompanied with pain. Ulceration and paresthesia or anesthesias are commonly reported symptoms. One study found these lesions frequently misdiagnosed as odontogenic infections.83-88
BENIGN CYSTIC AND NEOPLASTIC LESIONS OF THE JAWS
Intraosseous benign cysts and tumors are typically classified as either odontogenic, meaning arising from tooth-forming tissues, or nonodontogenic. Most odontogenic cysts in children are associated with impacted teeth and are most frequently discovered from dental radiographs. Occasionally, these cysts will cause localized expansion that may be evident clinically. One odontogenic cyst of particular concern is the odontogenic keratocyst, which typically is multiple when associated with basal cell nevus syndrome. These cysts have a relatively high recurrence following excision. The nonodontogenic cysts and tumors that may present with facial enlargement include the aneurysmal bone cyst, fibro-osseous lesions, fibrous dysplasia, cherubism, and central giant cell granuloma. Biopsy is necessary to establish a definitive diagnosis.99
ATTRITION AND EROSION
After the initial mineralization process, tooth structure may be lost from a myriad of factors besides caries and traumatic fracture. These mechanisms include attrition, abrasion, and dental erosion (eFig. 378.2 ).
Attrition is loss of tooth structure caused by tooth-to-tooth contact during mastication and occlusion. When the amount of tooth loss is extensive, it may begin affecting the appearance and function of the primary or permanent dentition. This wear may present in the form of habitual bruxism or involuntary grinding of the teeth. Bruxism is defined as an interruption of the normal rest position of the mandible during rest or sleep resulting from the forceful, rhythmic contractions of the masticatory musculature. It can be potentially harmful to the health of the oral tissues and restorative work. The prevalence of bruxism in children noted in the literature varies from 7% to 88%.86-89 This has been reported to occur in association with parasomnial activity and various dental, mental, neurological, and psychological risk factors. It has also been noted as a factor of other dental conditions such as malocclusion, eruption, or localized conditions, including mobile teeth, cuspal interferences, high restorations, and occlusal disharmony.89-91
Dental erosion is an irreversible dental hard-tissue loss due to acid exposure in the absence of bacterial involvement. Erosion may be caused by intrinsic factors, including recurrent vomiting (as in bulemia nervosa), regurgitation, gastroesophageal reflux (GER), or rumination. Extrinsic sources of acid are also possible causes of dental erosion such as diets composed of acidic foods and drinks, carbonated beverages, and alcohol. Continuous ingestion of acidic medications like chewable vitamin C and aspirin are also known causes of dental erosion.92,93
Gastroesophageal reflux has been associated with varying degrees of dental erosion of both the primary and permanent dentition.92-96
DISCOLORATION AND STAINING
The color of normal teeth varies and can be affected by a variety of factors, such as hygiene practices, diet, habits, bacteria, and underlying medical conditions. This discoloration can be classified as either extrinsic or intrinsic in nature (eFig. 378.3 ). Extrinsic stains, or superficial pigmentation of the enamel, are caused by such things as bacterial stains, tobacco, foods, restorative materials, and medications like iron supplements. Generally they can be removed with a thorough dental prophylaxis.
Intrinsic stains are secondary to endogenous factors, resulting in discoloration of the dentin. These may be secondary to hereditary conditions such as amelogenesis or dentinogenesis imperfecta. They may also be attributed to dental fluorosis, erythropoietic porphyria, hyper-bilirubinemia, and medications. Historically, tetracycline use in pregnant women and young children was one of the more common etiologies of intrinsic staining. Their ability to cross the placenta barrier and chelate calcium results in staining of both teeth and bone in the developing fetus and child.
FUSION AND GEMINATION
Fusion and gemination refer to two distinct conditions resulting in a similar clinical appearance of “twinned” or “double tooth.” They represent disturbances in the morphodifferentiation stage of tooth development.
Gemination is an attempt of a single tooth bud to divide, resulting in an incomplete formation of both the teeth and their clinical crowns. This may result in crowns that are partially or totally separate but have a single root canal. The total tooth count is normal. Fusion, however, is a complete joining of enamel or dentin of two distinct tooth buds. Usually there is one fewer tooth, unless this fusion occurs with an extra or supernumerary tooth. Fusion and germination are seen more commonly in the primary than in the permanent dentition.
HYPODONTIA
Congenitally missing teeth (tooth agenesis) are one of the most common dental diagnoses in the pediatric population. Missing teeth can occur in isolation or may be associated with an underlying syndrome or medical condition and can range from complete anodontia (all teeth) to hypodontia (one or more teeth). Additionally, these dental anomalies have been reported in children who have cleft lip, cleft palate, ectodermal dysplasia, Down syndrome, and Hallermann-Streiff (oculomandibulofacial) syndrome.
The most common missing permanent teeth are third molars, with prevalence rates reported at 9% to 37%. This is followed by mandibular second premolars and maxillary lateral incisors, depending on the population studied.
SUPERNUMERARY TEETH/HYPERDONTIA
Supernumerary teeth and conditions of hyperdontia occur when there is more than the normal complement of primary or permanent teeth. Overall, the prevalence of supernumerary teeth ranges from 1.5% to 3.9%. Single-tooth hyperdontia is most commonly found in the anterior maxillary region in the form of a mesiodens. A mesiodens is a supernumerary tooth (or teeth) that is present in the maxillary midline between the permanent central incisors and is often an incidental finding on dental radiographs. It is usually located palatally to the permanent incisors and may interfere with eruption or, if the incisors erupt, may result in a malposition. In the absence of timely eruption of the maxillary permanent incisors, referral to a pediatric dentist is appropriate, and removal may be necessary. Occasionally, supernumerary teeth may be found in the primary dentition and may signal the presence of extra permanent teeth as well.
Multiple supernumerary teeth may be a feature of several syndromes, including Gardner’s syndrome, cleidocranial dysplasia (CCD), cleft lip and palate, Hallermann-Streiff, Down syndrome, and chondroectodermal dysplasia.