Cleidocranial Dysostosis, Unilateral Sensorineural Hearing Loss and Gait Disturbances: A Clear-Cut Case of Diagnostic Mimicry?

Sir,

Cleidocranial dysostosis was accurately described for the first time in 1871 [[3]]. It is inherited as an autosomal-dominant trait and was mapped to the chromosome 6 p21 [[3], [5]]. Recently, the human CBFA1 gene was identified as the corresponding gene [[2]]. It is characterised by patent fontanelles, wide cranial sutures, hypoplasia of the clavicles, short stature, supernumerary teeth, and other skeletal anomalies [[3]]. No consistent neurological abnormality has been associated with this disorder, although epilepsy and mental retardation has frequently been noted. Conductive deafness is common secondary to malformations of the cartilaginous structures and membranous bones of the middle ear. With exception of one spinal schwannoma [[4]], no central nervous system tumours or neoplastic features have been recorded thus far in patients with cleidocranial dysostosis.

We report on a case of a 16-year-old girl with a history of familial cleidocranial dysostosis (the girl's father and grandfather suffered from this disorder, both without neurologic involvement or hearing impairment). She exhibited typical features of this disorder, including dental dysplasia, maldevelopment of the clavicles, megalencephaly with open fontanelles, and cephalopelvic disproportion with bowlegs. At the age of 15 years, she underwent varisation osteotomy of the hips in another hospital. The postoperative course was complicated by a sudden loss of hearing with consecutive sensorineural hearing loss on the left side. Six months later, for the first time, she complained of disequilibrium with gait disturbances, rotatory vertigo, and headache. Despite progression of these symptoms and consultations of an ENT surgeon and a neurologist in ambulatory settings, the girl's complaints were attributed to the underlying disorder, e.g., possible malformations of the cartilaginous structures and membranous bones of the middle ear. Further diagnostic procedures were not performed. At the age of 16 years, she was admitted again to another hospital for removal of the metal osteosynthesis of the hips. Surgery was successfully performed, but the girl did not awake from general anaesthesia. Therefore, she was transmitted to our paediatric intensive care unit. On admission, she was stuporous and presented with abducens nerve palsy on the left side. Cranial magnetic resonance imaging showed hydrocephalus internus and a large tumour in the region of the left cerebellopontine angle (Fig. [1]) with a small branch into the internal auditory canal. Two days later, the tumour was totally resected. Histologic evaluation revealed a schwannoma WHO grade I. The post-operative course was uneventful, and the girl was discharged home ten days later in apparently good health.

Fig. 1 Gadolinium-enhanced coronal T₁-weighted magnetic resonance image: Oval-shaped tumour with homogenous contrast enhancement and compression of the cerebellum and brain stem.

The girl presented in this case report developed a sudden loss of hearing with sensorineural hearing loss after varisation osteotomy of her hips. Six months later, she complained of disequilibrium with gait disturbances, rotatory vertigo, and headache. These symptoms were erroneously attributed to her underlying disorder, not taking into account that these symptoms typically indicate a labyrinthine or cerebellar disorder. Why the girl did not awake from general anaesthesia after her second operation remains unclear. Possibly, the use of halothane or ketamine in a patient with an unrecognised elevation of intracranial pressure may have led to a further increase of intracranial pressure and, consecutively, to this comatose state [[1]]. Nevertheless, this accident forced us to perform a brain imaging, first bringing up the diagnosis of an eighth nerve (vestibular) schwannoma, which has not been described in patients with cleidocranial dysostosis before. Furthermore, this case report impressively demonstrates a possible pitfall emerging from overlooking characteristic symptoms of an intracranial space-occupying lesion in the face of similar symptoms that were attributed to a known and underlying disorder, although only a conductive hearing loss should have been anticipated in a patient with cleidocranial dysostosis.

References

• 1 Dayrell-Hart B, Klide A M. Intracranial dysfunction: Stupor and coma.  Vet Clin North Am Small Anim Pract. 1989;  19 1209-1222
• 2 Mundlos S, Otto F, Mundlos C, Mulliken J B, Aylsworth A S, Albright S. et al . Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia.  Cell. 1997;  89 773-779
• 3 Mundlos S. Cleidocranial dysplasia: Clinical and molecular genetics.  J Med Genet. 1999;  36 177-182
• 4 Pattisapu J, Miller J D, Sanford R A. Cleidocranial dysostosis and schwannoma.  Neurosurgery. 1986;  18 827-828
• 5 Zhang Y W, Yasui N, Ito K, Huang G, Fujii M, Hanai J. et al . A RUNX2/PEBP2αA/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia.  Proc Natl Acad Sci USA. 2000;  97 10549-10554