Recurring gnathodiaphyseal dysplasia in two Russian brothers

Abstract

Two Russian brothers presented with recurring benign facial bone tumors and progressive limb bowing. The association of fibro-osseous jawbone lesions and long-bone bowing with cortical thickening suggested the diagnosis of gnathodiaphyseal dysplasia, in the absence of arguments in favor of fibrous dysplasia. Gnathodiaphyseal dysplasia is a rare autonomic dominant syndrome due to a mutation of the TMEM16E gene. The extreme and recurring phenotype of these two patients illustrates the variable expressivity of this disease. Differential diagnosis with other benign facial bone tumors is discussed.

The association between benign facial bone tumors and long-bone anomalies is strongly suggestive of polyostotic fibrous dysplasia (FD), or of McCune-Albright syndrome if endocrine disorders and abnormal skin pigmentation are reported (MAS, OMIM #174800). Fibro-osseous lesions of the jawbones occurring in conjunction with postcranial skeletal deformations are described in other extremely rare cases.

The authors report the case of two Russian brothers presenting with facial tumors resembling familial cemento-osseous dysplasia (COD) and long-bone malformations associated with bowing and cortical thickening. This phenotype was suggestive of gnathodiaphyseal dysplasia (GDD, OMIM #166260), a recently identified syndrome .

GDD is part of a pathological spectrum of benign facial bone tumors including FD/MAS, COD and cemento-ossifying fibroma (COF) . The main problem with GDD is the differential diagnosis with FD/MAS . GDD has distinctive long-bone lesions and specific pathological characteristics, but its natural history, and in particular the risk of associated malignancies, is poorly known due to the very low prevalence of the disease . GDD is caused by mutations in the TMEM16E (transmembrane protein 16E) gene , while FD is caused by activating missence mutations of the GNAS1 (guanine nucleotide binding protein, α-stimulating 1) gene . The two cases reported here document the evolution of GDD over 15 years and underline its clinical, radiological and pathological specificities.

Case report

An 8-year-old boy from the region of Rostov-on-Don in South-Western Russia was admitted in 1998 for a mandibular mass that had been increasing in volume for the last 5 years. He had under gone a subtotal mandibulectomy at the age of 3 years. Pathology reports showed non-specific fibro-osseous jawbone lesions. When the patient was first referred, the tumor had recurred and needed a secondary surgical treatment. A subtotal mandibulectomy with reconstruction using a titanium plate was performed ( Fig. 1 ). 6 years after surgery, in 2004, a large maxillary tumor had developed and required a third operation ( Fig. 2 ). In 2007, the evolution of the facial tumors seemed to have stopped ( Fig. 3 ), but during the previous 4 years, severe bowing of the long bones and deformation of the thoracolumbar spine had occurred ( Fig. 3 ), causing scoliosis and a pathological fracture of the left radius and ulna in 2004.

Fig. 1
Older brother. Clinical and gross pathological aspect of the jawbone tumor at 8 years of age: mandibular overgrowth, teeth loss and ‘Akenathen chin’ aspect.

Fig. 2
Older brother. Clinical, radiological and gross pathological aspect of the jawbone tumors at 14 years of age: asymmetrical maxillary overgrowth; mandibular reconstruction using a titanium plate performed at the age of 8 years.

Fig. 3
Older brother. Bowing of long bones and scoliosis at 17 years of age.

The patient’s brother, born in 1992, presented with a mandibular tumor in 2002 and a maxillary tumor in 2005. Between 2005 and 2007, the volume of both tumors steadily increased ( Fig. 4 ). At the age of 14 years, pathological fractures of the lower extremities and of the right radius and ulna required surgical treatment ( Fig. 4 ). In 2007, he benefited from subtotal mandibulectomy. Pathological examination showed a cemento-ossifying fibroma in its psammomatoid variant ( Fig. 5 ). Surgery of the maxillary tumor is planned for 2009.

Fig. 4
Younger brother. Mandibulary overgrowth and long-bone bowing at 15 years of age; pathological fractures of the right radius and ulna.

Fig. 5
Younger brother. 15 years of age. Standard profile skull X-ray and CT scans showing overgrowth and dysplastic changes of the mandibulary and maxillary bones in tooth-bearing areas, with radiolucent lines between teeth and radio-opaque lesions; the maxillary sinuses are filled with pathological tissue; the tiny scattered radio-opaque spots correspond to psammomatoid bodies; pathology shows fibro-osseous lesions with scattered psammomatoid bodies.

Both brothers had normal height and weight for their age. They were free of endocrine disorders and their cognitive development was not affected. Neither of the patients had café-au-lait skin pigmentation, Lish nodules or neurofibroma. Sclera were white in both cases. No joint hypermobility was reported. The tumoral lesions were not tender at any stage of their evolution. The biochemical markers of bone metabolism were normal. Owing to the lack of material, genetic screening for the GNAS1 and the TMEM16E genes was not carried out.

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Feb 8, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Recurring gnathodiaphyseal dysplasia in two Russian brothers
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