Syndromes Affecting Bone

Key points

  • Look beyond the primary jaw pathology for clues of syndromic involvement. Observe the skin, and always consider extrafacial skeletal involvement.

  • Study Gorlin’s Syndromes of the Head and Neck and similar references to increase your “rolodex” of known syndromes.

  • Review the natural history of the pathology and develop a perspective for whether there is an active process and/or a progressive process.

Introduction

This article is a clinical description of genetic diseases that affect facial bones, giving rise to dysmorphic facies. It is by no means complete, rather it is meant to serve as an outline of skeletal anomalies that can provide structure for oral and maxillofacial surgeons to screen the patients that they encounter. The reader should have access to other sources, such as Gorlin Syndromes of the Head and Neck , Sixth Edition; Smith’s Recognizable Patterns of Human Malformation by Jones; and The Management of Genetic Syndromes by Cassidy and Allanson.

When evaluating bone diseases of the jaws and considering a syndromic etiology, the clinician needs to first characterize what is observed. Is the process radiolucent or radiopaque? Does this condition result in skeletal dysplasia, hyperplasia, or hypoplasia? Is this a local, monostotic, regional, or polyostotic phenomena? Finally, what other abnormalities are present in this patient. Is this observed bony pathology a component of a constellation of findings, that is, a syndrome involving multiple pathologic entities? If there are multiple disorders, are they associated with potential for genetic transmission?

Although today there seems to be a limited number of conditions that affect the maxillofacial skeleton that are truly genetic in order, as our ability to understand the human genome and characterize individuals and their genetic sequence increases, undoubtedly many more clusters of genetically coded phenotypic expressions will be identified. In addition, what appears outwardly as an external independent source of disease or deformity may turn out to be genetically predetermined. For example, there is no doubt that medication-related osteonecrosis of the jaw (MRONJ) can be related to the use of bisphosphonates that inhibit osteoclast formation. However, it is becoming apparent that there are clusters of patients with genetic sequences that increase susceptibility to this class of drugs, rendering the patient increasingly susceptible to MRONJ. That being said, there are classic syndromes that affect bone and are associated with other physical abnormalities that are genetically transmitted. These are illustrated in this article.

Introduction

This article is a clinical description of genetic diseases that affect facial bones, giving rise to dysmorphic facies. It is by no means complete, rather it is meant to serve as an outline of skeletal anomalies that can provide structure for oral and maxillofacial surgeons to screen the patients that they encounter. The reader should have access to other sources, such as Gorlin Syndromes of the Head and Neck , Sixth Edition; Smith’s Recognizable Patterns of Human Malformation by Jones; and The Management of Genetic Syndromes by Cassidy and Allanson.

When evaluating bone diseases of the jaws and considering a syndromic etiology, the clinician needs to first characterize what is observed. Is the process radiolucent or radiopaque? Does this condition result in skeletal dysplasia, hyperplasia, or hypoplasia? Is this a local, monostotic, regional, or polyostotic phenomena? Finally, what other abnormalities are present in this patient. Is this observed bony pathology a component of a constellation of findings, that is, a syndrome involving multiple pathologic entities? If there are multiple disorders, are they associated with potential for genetic transmission?

Although today there seems to be a limited number of conditions that affect the maxillofacial skeleton that are truly genetic in order, as our ability to understand the human genome and characterize individuals and their genetic sequence increases, undoubtedly many more clusters of genetically coded phenotypic expressions will be identified. In addition, what appears outwardly as an external independent source of disease or deformity may turn out to be genetically predetermined. For example, there is no doubt that medication-related osteonecrosis of the jaw (MRONJ) can be related to the use of bisphosphonates that inhibit osteoclast formation. However, it is becoming apparent that there are clusters of patients with genetic sequences that increase susceptibility to this class of drugs, rendering the patient increasingly susceptible to MRONJ. That being said, there are classic syndromes that affect bone and are associated with other physical abnormalities that are genetically transmitted. These are illustrated in this article.

Osteopetrosis

Genetics

Osteopetrosis is autosomal recessive in its neonatal form and is often called marble bone disease. The autosomal dominant form, often called late onset, is more benign in its clinical nature and is divided into a Type 1 and Type 2 expression. The prevalence is about 1 in 250,000 births. There is a higher incidence of this condition in Costa Rica, Saudi Arabia, and Denmark (1/20,000).

Clinical features

Osteopetrosis is a generalized disease of bone in which there is failure of normal bone remodeling by resorption or an overproduction of bone. Various defects in osteoclast or osteoblast function have been implicated. As a consequence, the bone becomes dense and radiopaque with a radiographic homogeneity between the cortical and medullary bone ( Fig. 1 ). There are various clinical forms of this disease. The worst outcomes are seen with the neonatal form, Albers-Schönberg disease. This entity is generally fatal, although early bone marrow transplantation can slow the progression of the disease process. Most patients do not live beyond adolescence.

Fig. 1
Montage of patient with sclerotic bones associated with osteopetrosis. ( A ) Bowed femur. ( B ) Dense vertebra with lack of normal spine. ( C ) Sclerotic mandible with multiple unerupted molars. ( D–F ) Enlarged calvarium. ( G, H ) Sclerotic and thickened zygoma and mandible. ( I ) Diffuse ostesclerosis noted on chest x ray. ( J–L ) Radiodense feet, hands, and pelvis.
( From Xue Y, Wang W, Mao T, et al. Report of two Chinese patients suffering from CLCN7-related osteopetrosis and root dysplasia. J Craniomaxillofac Surg 2012;40:416–20; with permission.)

The progressive density of affected bones without a resorptive phase promotes early fracture and encroachment on the cranial nerve foramina resulting in diminished vision, hearing, and fifth nerve function. Extramedullary hematopoiesis may result in hepatosplenomegaly and pancytopenia. Facial deformities, including frontal bossing and broad face, occur along with delayed dental eruption.

Differential diagnosis

Although the infantile neonatal form presents with a unique clinical presentation, the benign form of the disease, which can affect the mandible, cranium, and cervical spines with a sclerotic process, needs to be differentiated from other forms of osteosclerosis, such as Van Buchens disease, osteopathia straita, and sclerosteosis.

Treatment considerations for the oral and maxillofacial surgeon

Many unerupted teeth may occur. More than 30% of cases develop osteomyelitis de novo after dental extractions ( Fig. 2 ).

Fig. 2
Draining cutaneous fistulae secondary to chronic osteomyelitis, a common finding when the osteopetrotic jaws are subject to trauma, including dental extractions.
( Courtesy of D. Sarasin, DDS, Cedar Rapids, IA.)

Osteopathia striata with cranial sclerosis

Genetic

This condition is classified as autosomal dominant or X-linked dominant.

Clinical features

Osteopathia straita is a bone disease that is characterized by enlarged sclerotic craniofacial bones. The facial appearance is square and broad. Although dense and enlarged, the midface lacks projection ( Fig. 3 A). The encroachment on the cranial foramina results in cranial nerve dysfunction ( Fig. 3 B). More than 50% of patients have hearing loss. Along with characteristic craniofacial changes, the long bones demonstrate a peculiar linear striation giving a combed-through appearance ( Fig. 3 C). Other craniomaxillofacial features include frontal bossing, hypertelorism, hearing loss, cleft palate, bifid uvula, and a dense cranial base ( Fig. 3 D). Temporomandibular joint ankylosis has been described.

Fig. 3
( A ) Patient with osteopathia striata; note the pseudo prognathism secondary to maxillary hypoplasia. ( B ) This 3-dimensional (3D) cone-beam computed tomography (CT) image demonstrates diffuse sclerosis of the facial bones, orbits, and mandible. As time progresses, the foramina may close around existing nerves, causing hypoesthesia or dysfunction. ( C ) Long bone of a patient with osteopathia striata. Note longitudinal linear striations, as well as fracture of distal fibula. ( D ) Lateral cephalogram in patient with osteopathia striata. Note markedly thickened skull base, obliteration of maxillary sinus with sclerotic bone and density to skull, mandible, and cervical spines.
([ C ] Courtesy of E. Winn, MD, Long Island, NY.)

Other systemic findings include ventricular septal defect, atrial septal defect, laryngeal tracheal malacia, polydactyly, and syndactyly. This condition is a frequent feature of focal dermal hypoplasia.

Differential diagnosis

The craniofacial presentation needs to be differentiated from osteopetrosis as well as other craniosclerotic syndromes. However, the unusual linear striations of the long bones are almost pathognomonic, but can be seen in benign forms of osteopetrosis.

Considerations for the oral and maxillofacial surgeon

The maxillary growth deficiency when combined with mandibular enlargement may cause dentofacial deformity, creating a consideration for orthognathic surgery. Attempts to osteotomize this bone for repositioning poses great difficulty and warrants careful consideration.

Infantile cortical hyperostosis: Caffey Silverman syndrome

Genetics

There is both a familial and sporadic form. It seems that this is an autosomal dominant abnormality with incomplete penetrance and variable expressivity. It has been associated with a defect in chromosome q21. It is a prenatal form that is said to be autosomal recessive and is more prominent and often associated with early cytology.

Clinical features

This acute inflammatory process occurs with remarkable symmetry associated with swelling of the jaws. It is seen in neonates and infants from the time of birth to 20 months of age. This disease is characterized by painful burning and swelling over the face and jaws ( Fig. 4 A). This swelling might also involve the thorax and extremities ( Fig. 4 B). This is an inflammatory process accompanied by fever, with elevated white blood cell count and increased sedimentation rate. According to Eversole, “The histology is one of elevated periosteal new bone formation.” This may be related to congenital anomalies of the vessels supplying the periosteum and causing the involved bones to be hypoxic, become necrotic, and create overlying soft tissue inflammation and eventually new bone formation in the periosteum ( Fig. 4 C).

Jan 23, 2017 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Syndromes Affecting Bone
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