Numb chin syndrome is a sensory neuropathy of the inferior alveolar branch of the trigeminal nerve, characterized by unilateral numbness of the chin, the lower lip and the buccal and gingival mucosa. We report a girl with acute lymphoblastic leukemia of B-cell type who initially presented with numb chin syndrome resulting from skull base infiltration.

Key words: B-ALL, Complications, Cranial nerve involvement, Numb chin syndrome.

A 9-year-old girl presented with a two week history of increasing fatigue, fever, night sweat and weight loss. Physical examination revealed firm and painless right-sided fronto-parietal swellings. There was no lymphadenopathy or hepatosplenomegaly. The girl also reported unilateral hypoesthesia of the left chin, the lower lip, and the gingival and buccal mucosa for one month. There were no other neurological symptoms. MRI of the head showed multiple bone lesions with contrast-enhancement of the extra- and intracranial soft tissue at different locations (frontal, right temporo-parietal, left sphenoid and left mastoid). Complete blood count was within normal limits, but LDH (2315 U/L) and uric acid (16.9 mg/dL) were highly elevated. Typical Burkitt blasts were seen in the blood smear and the bone marrow was completely replaced by blasts. Cerebrospinal fluid showed no evidence of leukemic cells. The patient was treated according to the prospective multicenter trial B-NHL BFM 04 with intensified central nervous system (CNS) treatment including repeated applications of intrathecal chemotherapy with prednisone, methotrexate, and cytosine arabinoside. She achieved complete remission after the first course of chemotherapy and the symptoms improved. Numb chin syndrome resolved completely after three courses of chemotherapy. Cranial lesions also decreased in size on follow-up MRI. The child achieved complete remission.

Numb chin syndrome in malignancies results from invasion of the mandibular canal or mental foramen by mandibular metastases or from invasion of the mental nerve and/or the alveolar nerve itself. In addition, subcutaneous mental metastasis or enlarged lymph nodes can cause compression of the inferior alveolar nerve before its entry into the mandibular canal. Metastatic infiltration of the proximal root of the mandibular nerve at the skull base and intracranial leptomeningeal invasion may also lead to NCS. "Paraneoplastic" NCS has rarely been described resulting from antibody production against the Gasserian ganglion [1].

The association of NCS with malignancies of B-cell type, as seen in our patient, is an interesting phenomenon. Fenaux, et al. [6] described 10 of 18 adult patients with B-ALL presenting with NCS. The authors considered that the presence of isolated NCS, which was observed in four patients, was diagnostic of CNS involvement and recommended additional CNS treatment for these patients. Kuroda, et al. [7] reported on the involvement of the trigeminal nerve root in a 57-year old man with Burkitt cell acute leukemia. They demonstrated heavy infiltration of leukemic cells and destruction of axons and myelin by leukemic cells in a post-mortem study of the trigeminal nerve.

Skull base infiltration is frequently observed in children with malignancies of B-cell type [5, 8-10]. Choi, et al. [10] reported four children with B-cell lymphoma experiencing visual disturbances or visual loss due to central skull base (sphenoid bone) involvement. Burkitt lymphoma involving the clivus has also been reported in three children; with two of them having sixth cranial nerve palsy [8]. Seixas, et al. [5] recently described the first case of skull base infiltration in a child with Burkitt leukemia and clinical signs of NCS. Cavernous sinus involvement led to paresis of the right oculomotor nerve and ultimately to NCS. Tumors of the clivus commonly present with diplopia and cranial nerve palsies, especially of the sixth cranial nerve. Other cranial nerves such as the trigeminal nerve exit the skull through the foramen ovale and might be damaged by skull base infiltration, giving the symptoms of NCS, as seen in our patient. Cranial MRI revealed leukemic infiltration of the sphenoid in our patient explaining the symptom of numb chin syndrome. This was interpreted as cranial nerve infiltration. Therefore, a more intensive CNS therapy was administered in this patient.

We conclude that NCS in children with malignancies of B-cell type, with or without detectable infiltrations of the skull base, should be interpreted as cranial nerve involvement and consequently treated with intensified CNS therapy.

Contributors: JP: Primary responsibility for acquisition of data and writing the manuscript. She will act as guarantor of the case report. HL: drafted the case report and helped to write the manuscript; MB and CU: revised the article critically for important intellectual content. The final manuscript was approved by all authors.

Funding: None.

Competing interests: None stated.

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