The Genetically Based Diseases of the Jaw in Childhood: A Clinical Review

Review Article

Austin J Musculoskelet Disord. 2014;1(2): 1007.

The Genetically Based Diseases of the Jaw in Childhood: A Clinical Review

Picco P1, D’Alessandro M1* and Leoni M1

1Department of Pediatric Rheumatology, G. Gaslini Institute, Italy

*Corresponding author: D’Alessandro M, Department of Pediatric Rheumatology, G. Gaslini Institute, Largo Gaslini 5, 16147, Genoa, Italy

Received: August 06, 2014; Accepted: August 25, 2014; Published: August 26, 2014


Mandibular bone lesions may be the major symptom of several pediatric diseases with different etiology and severity. Some genetic disorders may herald with mandibular involvement: this unusual site of localization often represents a misleading clinical feature. Herein we review this topic focusing on the clinical and radiologic aspects. Moreover some differential diagnosis issues with mandibular lesions caused by infectious, inflammatory or neoplastic processes are discussed.

Keywords: Fibrous Dysplasia; Infantile Cortical Hyperostosis; Majeed Syndrome; Cherubism; Osteomyelitis


ICH: Infantile Cortical Hyperostosis; FD: Fibrous Dysplasia; MAS: McCune-Albright Syndrome; MS: Mazabraud Syndrome; CNO: Chronic Non-Bacterial Osteomyelitis; CDA: Congenital Dyserythropoietic Anemia; PD: Pustular Dermatosis; TRAP: Tart rate-Resistant Acid Phosphatase; DIRA: Defect Of Interleukin 1 Receptor Antagonist; CRMO: Chronic Recurrent Multifocal Osteomyelitis; SAPHO: Synovitis Acne Pustulosis Hyperostosis and Osteitis; STIR: Short Tau Inversion Recovery; JMCO: Juvenile Mandibular Chronic Osteomyelitis; ABC: Aneurismal Bone Cyst


Under the term of genetic mandibular disorders are gathered different diseases which are relatively uncommon in children and clinically heterogeneous for age of onset, severity and outcome. Although some of them are known from decades, only recently the causative genes of these disorders have been identified: furthermore the underlying pathophysiological mechanisms remain still poorly understood.

It is noteworthy that different stages of bone formation and remodeling as well as differentiation of stem/progenitor cells, matrix production, mineralization or bone desorption may be negatively affected [1]: despite the primary bone damage of these genetic disorders concerns the jaw morphogenesis, their clinical symptoms are usually characterized by an inflammatory lesion (severe pain, swelling, skin redness and warmth, limitation of movement such as difficulty in opening the mouth or chewing etc) mimicking more common bone diseases (e.g. infectious osteomyelitis, inflammatory osteitis, fractures, tumors): hence it is likely that inherited jaw disorders might be underdiagnosed.

As the number and the function of many genes encoding for proteins involved in bone metabolism are still to be defined, at present the clinical and instrumental criteria still represent the more useful tools in addressing towards the correct diagnosis. Conversely, the pediatricians must always have in mind these orphan diseases in the physical examination of a patient with inflammatory involvement of the jaw. A careful clinical evaluation of the patient is mandatory, searching for systemic (e.g. fever, widespread bone pain, weight loss) or extra-skeletal (e.g. precocious puberty, café-au-lait skin lesions) findings which have a pivotal role for the diagnosis. Furthermore biological assessment of calcium phosphate metabolism and imaging study (local and systemic) are useful diagnostic tools; bone biopsy still represents the gold standard for evaluating the structure and ruling out infectious or malignancies.

Molecular analysis, as a definitive diagnostic classification, may be proposed in selected cases on the basis of the above-mentioned clinical and instrumental evaluation.

Herein we synthetically review the genetically-based mandibular disorders that have their onset in pediatric age highlighting their clinical and radiological features: a large section will be focused on the differential diagnosis of these conditions and the most common misleading pitfalls.

Mandibular Disorders

Infantile cortical hyperostosis

Infantile Cortical Hyperostosis (ICH) is a rare cause of jaw swelling in early infancy. The disease, firstly reported by Roske [2] in 1930, was more extensively studied by De Toni in 1943. This pioneer of pediatrics and scientific founder of G Gaslini Institute where we are working are credited with having fully described the clinical aspects and recognized its genetic nature [3]. Caffey and Silverman reported other cases, reviewed their clinical and radiographic features and coined the term of infantile cortical hyperostosis [4,5].

Typically ICH occurs in the six months of postnatal age and no later than the second year of life. The babies affected disclose soft tissue swelling, bone hyperostosis with a clear subperiosteal hyperosteogenesis. Mandible is the most commonly involved bone: clavicle, radius and ulna, tibia and femur may be also affected. Since fever, severe bone pain, irritability and acute phase reactant positivity are usually found [6], ICH may be misdiagnosed with different disorders such as infectious osteomyelitis or autoinflammatory bone disease. A positive family history for a so-called neonatal osteomyelitis is an important diagnostic aid.

The disease has generally a benign, self-limiting course and its signs and symptoms spontaneously recover within few months without clinical recurrence: a bone scar may occasionally persist [7]. It is of note that anecdotal cases of ICH with recurrence during adolescence have been recently reported [8]: upon this finding, ICH should be considered in all pediatric patients suffering from auto inflammatory bone disorders.

The radiographic hallmarks of ICH is constituted by a typical subperiosteal cortical hyperostosis leading to an increase of cortical width and density associated to a laminated, well defined subperiosteal bone apposition [9]. The bone involvement have an asymmetrical multifocal distribution: rarely it is possible to observe widespread diffusion with a predominant inflammatory component [10] or atypical features, such as the coexistence of tumoral calcinosis [11].

In 2005 Gensure et al. [12] found that ICH patients are heterozygous for missense mutation 3040C/T in axon 41 of the gene COL1A1 altering residue 836 (R836C) in the triple-helical domain. This finding has been confirmed in other patients including a wide Italian family.

Although allelic COL1A1 mutations have been reported in Ehlers Danlos syndrome and osteogenesis imperfecta, individuals with R836C mutation do not have clinical features suggestive for these latter diseases.

More recently a prenatal-onset ICH case has been reported [13]: however the severe and persistent bone involvement, the absence of clinical inflammation and the not well-defined etiology suggest this ICH-like phenotype may be an independent clinical entity rather than a variant of ICH [14].

Fibrous dysplasia

Fibrous Dysplasia (FD) is a genetic not-inherited bone disorder that may affects both male and female patients. The actual prevalence of the disorder is difficult to assess considering that the disease is often misdiagnosed because of its subclinical course: anyway it has been roughly calculated that 5% to 7% of mandibular benign bone tumors are due to FD [15,16].

The disease may have a monostotic (70% of the cases) as well as a polyostotic course: usually the diagnosis is made before 30 years of age. The polyostotic variant is more frequent in younger patients. At present there is no evidence supporting a progression from monostotic into polyostotic form [17,18]. Although lesions may develop ubiquitously, skull and namely jaw is the most common site of localization [19-21].

Citation: Picco P, D’Alessandro M and Leoni M. The Genetically Based Diseases of the Jaw in Childhood: A Clinical Review. Austin J Musculoskelet Disord. 2014;1(2): 1007. ISSN:2381-8948