Autosomal dominant stapes fixation, syndactyly, and symphalangism in a family with NOG mutation: Long term follow-up on surgical treatment
Introduction
Syndromic congenital stapes fixation is rare, but can cause conductive hearing loss with early onset. In 1990, Teunissen and Cremers reported data on a family with conductive hearing loss caused by stapes ankyloses [1]. The affected family members had severe hyperopia, broad thumbs and first toes, brachytelephalangia and, in one case, symphalangism. The syndrome was reported within several other families and named Teunissen-Cremers syndrome [2,3]. Nine years later, genetic analysis found a mutation in the NOG gene to be responsible for the syndrome [4].
Since the first presentation of a mutation in the NOG gene, more than 35 mutations have been identified causing overlapping variations of the syndrome: Teunissen-Cremers syndrome [[1], [2], [3]], Proximal symphalangism [[5], [6], [7], [8]], Multiple synostoses syndrome/facioaudiosymphalangism syndrome [[6], [7], [8], [9], [10], [11], [12]], Tarsal-carpal coalition syndrome [8] and Bradydactyly type B [13]. In addition to heterogeneity among the syndromes, there are inter- and intrafamilial variations in phenotypes [8,10,14,15]. Consequently, it can be difficult to distinguish between the syndromes and clinical diagnoses and an unifying term, NOG-related symphalangism spectrum disorder (NOG-SSD), has been introduced [16].
The NOG gene encodes the protein Noggin which inactivates bone morphogenetic proteins (BMPs). Absence of Noggin increase BMP-activity, resulting in recruitment of the cartilage cells, hyperplasia and bone growth [17]. Patients with stapes ankyloses caused by NOG mutation and morphological changes in Noggin may have an increased risk of refixation of stapes after surgery [18].
The aim of this study is to present long term audiological results after stapedectomy in a Danish family with a NOG mutation not earlier described.
Section snippets
Ethics
The study was conducted in accordance with the Danish law for scientific ethics committee and approved by the Danish Data Protection Agency. Informed consent was obtained from all included patients or from parents of the children.
Subjects
The family was presented by P. Vase et al., in 1975, where five family members had a syndrome with conductive hearing loss, syndactyly and symphalangism [19]. At this follow up study, there were eight affected family members in four generations. The pattern of
Otologic and audiologic findings
None of the individuals had a history of trauma or noise damage. Two of the affected patients (II:2 and IV:2) had an anamnesis with middle ear infections. Patient IV:2 had tubulation of both tympanic membranes at the age of 2 years. The tympanic membrane was healed at the time of examination and there was no suspicion of glue or infection in the middle ear. Three patients (III:1, IV:1 and III:2) had gone through stapedectomy on one or both ears at the time of examination. The ears (n = 5) who
Discussion
Congenital or early onset of conductive hearing loss is rare. However, mutations in NOG can result in stapes ankyloses and conductive hearing loss. A wide range of mutations in NOG have been described, all resulting in autosomal dominant syndromes with various affection of joints and hearing loss [2,3,6,14,15,26,27]. The variety of phenotypes combined with relatively few patients in all ages complicates studies on epidemiology, treatment and prognosis.
In this study, we presented a family with
Conclusion
Though conductive hearing loss in children is most likely due to otitis media serosa or other affections in the middle ear, NOG mutations can cause early onset of conductive hearing loss. Family history and genetic testing may be useful in discriminating in these cases. Clinical findings and a family history of conductive hearing loss should lead to further evaluations. The literature is not consistent on the longterm effect of surgery, but results of this study indicates that stapedectomy may
Conflict of interest statement
None of the authors have any conflicts of interest and no funds have been granted.
Acknowledgement
We are grateful to the family members for their participation. We thank Poul Vase for early attention on the family and the syndrome, and Claus Barfoed for video and surgical reports.
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