Hamartomas of the Tuber Cinereum Associated with X-Linked Deafness Show Signs of Pubertas Tarda Instead of Pubertas Praecox and No Gelastic Seizures-Long-Term Follow-Up of 12 Years.

ABSTRACT

PURPOSE: Hamartomas of tuber cinereum present as ectopic tissue in the hypothalamic region. Clinically, the usual hypothalamic hamartomas manifest themself by gelastic seizures and pubertas praecox. We observed an increased coincidence of the presence of X-linked recessive deafness DFNX2 (DFN3) and a hamartoma of the tuber cinereum. Initially five patients presented with hearing loss in childhood, two additional were already adults, not showing any characteristic symptoms for a hamartoma but signs of delayed puberty. METHODS: Seven patients who underwent computed tomography imaging due to a sensorineural hearing loss and had a hamartoma of the tuber cinereum in addition to X-linked deafness DFNX2 (DFN3) were included in a retrospective study. Patients underwent initial neurologic, endocrinologic, and genetic evaluation. Long-term follow-up was performed after 10 to 12 years. RESULTS: The average age at the initial exam was 12.9 years (range 4-29). All patients genetically proven nonsyndromic, X-linked deafness associated with the POU3F4 gene. Three out of six patients presented signs of delayed puberty. None of all seven showed any evidence of pubertas praecox or gelastic seizures at mean age of 17 years (range 17-29 years) at any time. CONCLUSION: Hamartomas of tuber cinereum are often coincident with DFNX2. Clinically, half of the cases are-in contrary to the usual pubertas praecox-associated with growth hormone deficiency and delayed puberty, in the sense of pubertas tarda, when coincident. Clinicians' and radiologists' knowledge and awareness of this rare combination are crucial to identify children early enough for hormone-sensitive treatment.