17 Developmental Defects of the Craniofacial Complex and Orthopedic Disorders


Developmental Defects of the Craniofacial Complex and Orthopedic Disorders

J. Timothy Wright DDS, MS

Michael Milano DMD

Luiz Andre Pimenta DDS, MS, PHD

I. Background

Dentists are confronted with diagnostic and treatment challenges for patients with hereditary conditions and unique environmental exposures. Developmental and hereditary disorders vary in their prevalence, morbidity, and need for unique oral health-care management approaches. Providing optimal oral health care is predicated on having a basic understanding of the patient’s underlying systemic and craniofacial condition, their current and future risk for developing oral pathology, and having the skills to manage their oral health needs. Depending on complexity, this can involve a team of oral and medical health-care providers. This chapter reviews some of the more common hereditary conditions affecting the skin, teeth, and bones, and presents dental management approaches.

Description of Disease/Condition

Hereditary Conditions Affecting the Teeth

Thousands of genes are expressed during tooth formation, so it is not surprising that there are many diverse hereditary conditions known to affect teeth. The defects can manifest as changes in the number, shape, size, and/or composition of the teeth. These conditions are genetically and clinically diverse in their presentations and can occur as part of a syndrome or can be isolated to the teeth. Two of the better known hereditary conditions affecting the composition and structure of teeth are amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DGI). These conditions can be challenging to diagnose and manage depending on the specific subtype and its manifestations.

Amelogenesis Imperfecta (AI)

  • Most commonly classified into three main categories based on the nature of the enamel defect.1
  • Hypoplastic: thin enamel (see Fig. 17.1).
  • Hypomineralized: hypocalcified or hypomaturation.

Figure 17.1 Hypomaturation amelogenesis imperfecta in a young female.


Dentinogenesis Imperfecta (DGI)

DGI and dentin dysplasia type II (DD-II) are the most common hereditary dentin disorders and have an autosomal dominant inheritance. DGI can occur in association with osteogenesis imperfecta (OI) (type DGI-I) or as an isolated defect of teeth (type DGI-II) (see Fig. 17.2).

Figure 17.2 Blue-gray coloration, enamel fracturing, and severe attrition associated with DGI-II.


Hereditary Conditions Affecting the Skin

Many hereditary conditions affect the development of the skin and/or the ectoderm and its appendages. Affected individuals can have increased fragility of the skin or have a lack of development of ectodermally derived appendages and thus can have altered tooth formation.

Ectodermal Dysplasias (EDs)

  • Characterized by abnormal development of ectodermally derived tissues, such as skin, hair, nails, sweat glands, and dentition (see Fig. 17.3).
  • The current definition of an ED is any condition having two or more affected tissues that are of ectodermal origin.

Figure 17.3 Conical-shaped incisors and hypodontia in an X-linked hypohidrotic ectodermal dysplasia (HED) affected 4-year-old male.


Epidermolysis Bullosa (EB)

  • Represents a spectrum of conditions having blistering and mechanical fragility of the skin as their hallmark feature (see Fig. 17.4).
  • Given the developmental and structural complexity of the skin, it is not surprising that there is tremendous genetic heterogeneity and marked phenotypic variation in the EB disorders.

Figure 17.4 Blistering of the skin and oral mucosa in a patient with recessive dystrophic epidermolysis bullosa.


Orofacial Clefts (OFCs)

OFCs are congenital malformations characterized by incomplete formation of structures involving the nasal and oral cavities: lip, alveolus, hard and soft palate. OFC may also vary in size, from a defect of the soft palate only to a complete cleft that extends through the bone of the hard palate. Because the lips and the palate develop separately, it is possible for a child to be born with a cleft lip (CL) only, cleft palate (CP) only, or the combination of both cleft lip and palate (CLP) (see Fig. 17.5).

Figure 17.5 Frontal view of a newborn with unilateral complete cleft lip and palate (a); occlusal view of the cleft palate (b).

(courtesy of Dr. Pedro Santiago—Director of Orthodontics and Craniofacial Orthodontist, Duke Cleft/Craniofacial Team)


Facial clefting variations
  • Cleft lip (cheiloschisis, CL)
  • Cleft palate (palatoschisis, CP)
  • Cleft lip and palate (cheilopalatoschisis, CLP)
  • Submucous cleft palate (SCP)

Defects of the Limbs and Skeleton

Amputation or “removal of a limb or other appendage of the body,” may be related to a surgical procedure or a vascular disturbance. Congenital “amputations” or developmental limb abnormalities are the result of growth inhibition during intrauterine development and are very diverse in their etiology.
Spinal Cord Injuries: Spinal cord injuries can be due to flexion, extension, or compression injuries to the spine. The location of the trauma has a direct impact on the individual’s functional deficit. Table 17.1 indicates the relationship between the level of the injury and the resulting functional deficit.
Scoliosis: Scoliosis is a lateral curvature of the spine, often with some rotation of the vertebrae. It ranges from mild to severe, and the degree of curvature can worsen over time. There are many diverse etiologies of scoliosis with a high percentage of cases in children being idiopathic.2
Spina Bifida: Neural tube defects are birth defects of the brain and spinal cord that are diverse in their etiology and clinical manifestations. The most common neural tube defect is spina bifida (myelomeningocele) where the fetal spinal column fails to close completely during the first month of fetal life.

Table 17.1. Clinical Features Related to Level of Spinal Cord Injury

Level of Spinal Cord Damage Associated Clinical Features
C1 to C4 Death secondary to respiratory paralysis
C4 to C5 Quadriplegia
C5 to C6 Arms paralyzed except for abduction and flexion
C6 to C7 Paralysis of hands and wrists but not arms
T11 to T12 Paralysis of legs above and below the knee
T12 to L1 Paralysis of the leg below the knee
S3 to S5 Loss of bladder and bowel control

C, cervical; T, thoracic; L, lumbar; S, sacral.

Physical manifestations of scoliosis
  • Lumbar area fatigue following extended standing or sitting
  • Muscular backaches
  • One hip more prominent than the other
  • One shoulder higher than the other


Hereditary Conditions Affecting the Teeth


There are seven genes known to cause AI, with several more likely to be identified in the near future and multiple phenotypes associated with allelic mutations in several of these genes. Collectively, the allelic and nonallelic AI-associated gene mutations result in many different AI types at the clinical and molecular levels. These genes all code for proteins that are important in enamel formation and mineralization.

Hereditary Dentin Disorders

  • OI
    • Associated with variable bone fragility that ranges from very mild to lethal at birth.
    • Caused by mutations in the genes that code for type I collagen and other genes involved in bone development.
  • DGI in association with OI (type DGI-I)
    • Associated with a marked decrease in dentin mineralization.
  • DGI as an isolated defect of teeth (type DGI-II)
    • Caused by mutations in the dentin sialophosphoprotein, a gene that codes for proteins that are critical for normal dentin mineralization.
    • Associated with a marked decreased in dentin mineralization.

Hereditary Conditions Affecting the Skin


There are many genes (over 50) known to cause ED, and many more will be discovered in the near future. Inheritance patterns include autosomal dominant, autosomal recessive, as well as the most frequently reported type, X-linked. If the mutated gene is critical for early oral epithelium events during tooth formation, such as invagination and proliferation of the oral epithelium, the result is likely to be missing teeth or hypodontia.


The most recent classification of EB identifies four major EB groupings (Table 17.2) and over 30 EB subtypes.3 The four major EB groups include intraepidermal EB (simplex), junctional EB, dermolytic EB (dystrophic), and mixed EB (Kindler syndrome).

Table 17.2. Epidermolysis Bullosa Phenotypes and Treatment


EB is caused by mutations in at least 14 genes.4 The causative genes for many of the EB subtypes code for proteins that are important in cell integrity, cell-to-cell adhesion and attaching the dermis and epidermis. Depending on the specific EB type, genetic mutation and thus missing or abnormal protein, there can be significant morbidity involving the soft and hard tissues of the craniofacial complex.

For example, Type VII collagen is critical for maintaining the integrity of the oral mucosa and skin. Consequently, individuals with Type VII collagen mutations (dystrophic EB) often have severely affected oral soft tissues that blister with minimal manipulation and frequently heal with scarring. Type VII collagen is not essential for normal tooth bud development so individuals with dystrophic EB typically have a normally developed dentition.

In contrast, laminin 332 is highly expressed during tooth development so individuals with mutations that affect laminin 332 function (junctional EB) have defects in the enamel of their teeth with generalized enamel hypoplasia. Individuals with recessive dystrophic and junctional EB are at increased risk for developing dental caries due to alterations in the soft tissue that make eating difficult and prolonged and home care difficult. The enamel defects in junctional EB produce additional risk for the development of dental caries.5


OFC is a defect of formation of the frontonasal process that gives rise to the nose, superior lip, maxilla, and primary palate, or is a defect of the fusion of the frontonasal process with the two maxillary processes. The pathogenesis of CL and CP is complex; the most widely accepted model is multifactorial inheritance, with interaction of genetic and environmental factors.6 Craniofacial defects such as CL and CP can occur as an isolated condition, or may be one component of an inherited disease or syndrome.

Defects of the Limbs and Skeleton

Amputation: Dysvascular amputations associated with diabetes account for the majority of amputations, more commonly affecting the lower extremities.7 This type of amputation has increased over the past several decades as the prevalence of diabetes has risen. Limb defects in newborns are highly variable in their etiology and manifestations of affecting digits and long bones.8 Vascular defects account for a high percentage of congenital limb defects.
Spinal Cord Injuries: The etiology of spinal cord injuries is diverse with trauma (automobile accidents, falls, and injury in sports activities or military service) being the most prevalent causes. Nontraumatic causes include arthritis, cancer, infections, or disk degeneration of the spine.
Scoliosis: Scoliosis can be divided into various categories based on etiology (congenital, paralytic, or idiopathic) or degree of curvature (functional or structural).9
Spina Bifida: This spinal defect is most commonly located in the lumbar, lower thoracic, or sacral regions and can involve up to six vertebral segments. Spina bifida has a multifactorial etiology with both environmental and genetic components. Maternal supplementation with folic acid during early pregnancy has helped reduce the frequency of this common developmental defect.10


Hereditary Conditions Affecting the Teeth


The AI conditions occur from about 1/700 to 1/15,000 depending on the population. It is believed that the prevalence in the United States is about 1:6000-8000.11

Hereditary Dentin Disorders

The prevalence of DGI-I is not known, although it is thought to occur in 30–50% of people with OI. DGI-III occurs in 1/8000 people in the United States.11 The incidence of DGI-I is 1/100,000.12

Hereditary Conditions Affecting the Skin


The hypohidrotic or ED types associated with diminished sweat gland formation are the most common.


The EB conditions are all rare with the milder forms (simplex) being more common than the severe forms.


OFCs are among the most common and treatable birth defects in the United States. Nonsyndromic OFC is the most common congenital malformation affecting on average of about 1/500–750 live newborns annually worldwide.13 CL with or without CP is the second most common condition in the United States, with an adjusted prevalence of 10.63/10,000 live births or 1/940 live births.14 The incidence of CL, with or without CP, varies among different ethnic populations and is presumed to be higher in developing countries. African-Americans have a lower prevalence rate compared with Caucasians.14 Risk factors that have been identified with CP include maternal behavior (including alcohol and tobacco use); nutrition, and multiple environmental exposures.15

Average prevalence of cleft lip and palate and number of births affected by these defects each year United States, 1999–2001
Prevalence* Annual Number of Cases
Cleft palate only 6.39 2567
Cleft lip with or without cleft palate 10.48 4209

* Prevalence per 10,000 live births.

Source: The Centers for Diseases Control and Prevention (CDC) National Birth Defects Prevention Network (NBDPN). 1999 to 2001 cleft lip and palate data collected from 11 states (Alabama, Arkansas, California, Georgia, Hawaii, Iowa, Massachusetts, North Carolina, Oklahoma, Texas, and Utah), adjusted for race-specific distribution of US live births.

Defects of the Limbs and Skeleton

Amputation: The prevalence of dysvascular amputations increases with the diabetic population age.7 Limb defects in newborns have a prevalence of about 0.8/1000 births.8
Spinal Cord Injuries: Overall males are more often afflicted than females. The prevalence is about 50/100,000 with cervical injury being the most common.16
Scoliosis: The U.S. adult prevalence of scoliosis is estimated at 8.3%, with women having twice the prevalence (10.7%) compared with men (5.6%).17
Spina Bifida: While it is reported that the worldwide incidence of all neural tube defects is thought to range from 1.0 to 10.0/1000 live births, spina bifida is one of the most common birth defects in the United States with a reported prevalence rate of 3.0–7.8/10,000 live births.18

c17uf001Coordination of Care between Dentist and Physician

Treatment of patients with OFC or other craniofacial anomalies is widely regarded as a multi-interdisciplinary enterprise from prenatal and family counseling through adulthood. Patients with other hereditary conditions of skin and bone may require consultation between dentist and physician to safely provide care to allow maintenance of the dentition. Referral to a physician for genetic testing may benefit patients with suspected hereditary conditions of the teeth and skin that may be first recognized in the dental office based on tooth appearance.

Treatment of OFC patients may involve craniofacial or cleft teams and centers, sometimes working in coordination with private practitioners. These centers provide a coordinated, multidisciplinary approach generally including experienced and qualified physicians and health-care professionals from different specialties, such as surgical (plastic and maxillofacial surgeons), ear, nose, and throat specialists; pediatric and general dentists; orthodontists; prosthodontists; speech therapists; psychologists; social workers; and allied health disciplines. Teams have become the standard in assessment and treatment of children with craniofacial anomalies like OFC.19 The role of dentistry in treating individuals with cleft and craniofacial anomalies is to provide comprehensive preventative and therapeutic oral health care.

c17uf002II. Medical Management

Identification/Medical History/Physical Examination/Laboratory Testing

Hereditary Conditions Affecting the Teeth


Genetic diagnosis is commercially available for several of the genes known to cause AI, thereby helping to confirm the diagnosis.

Hereditary Dentin Disorders

Several different tests are used to diagnose OI including evaluation of collagen formation by skin fibroblasts and gene sequencing. DGI-II is diagnosed clinically and can now be confirmed by gene sequencing.

Hereditary Conditions Affecting the Skin


Most individuals are diagnosed by their dermatologist using skin biopsies or in consultation with medical geneticists in the natal or neonatal period. Genetic testing can now be used to confirm most EB types.


Diagnosis is based on initial recognition of the predominant clinical features, which may be first noted in the medical or dental office. Molecular testing is available to confirm the diagnosis of many specific ED types.


Prenatal diagnosis can be performed at 13–14 weeks of gestation, when the soft tissues of the fetal face will be clearly visualized sonographically. Ideally, coronal view and axial planes are optimal for visualization of the fetal lip and palate in ultrasound images.20 Three-dimensional ultrasound21 and magnetic resonance imaging22 can also provide a clear image of the malformation and may enhance detection of isolated CP. Prenatal diagnosis of CLP is a reality today, and in cases of labial clefts detected during the prenatal period, parent’s psychological aspects can be discussed before the birth of the child. Not only technical preparation regarding the birth, but also a mor/>

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Jan 5, 2015 | Posted by in General Dentistry | Comments Off on 17 Developmental Defects of the Craniofacial Complex and Orthopedic Disorders
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