Teunissen-Cremers Syndrome: A Clinical, Surgical, and Genetic Report

Abstract

The Teunissen-Cremers syndrome is an entity in its clinical presentation, distinct from other syndromes with proximal symphalangism and hearing impairment. So far, in five families with Teunissen-Cremers syndrome, four truncating mutations and one amino acid substitution were found in the NOG gene. The majority of other mutations found in this gene are missense mutations, which might result in some residual protein activity. Reconstructive middle ear surgery is an option for treatment.

Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes

“…Hyperopia is another specific feature of NOG mutations, but high observation rate was found only in SABTT. Therefore, stapes ankylosis with high symphalangism and low hyperopia was sometimes categorized as proximal symphalangism-hearing loss syndrome (Weekamp et al, 2005). Taken together, the features of the present family showing a high prevalence of both stapes ankylosis and hyperopia could be classified as SABTT, rather than either SYM1 or proximal symphalangism-hearing loss syndrome.…”

“…Stapes ankylosis and symphalangism are some of the specific features in NOG mutations, and these features are recognized in not only in SABTTdwhich is mainly characterized by stapes ankylosis, hyperopia, broad thumbs and first toes, and hemicylindrical nosesdbut also in SYM1 and SYNS1. The observation rate of symphalangism was 5%e50% in SABTT, compared with 80%e87% in SYM1 and SYNS1 (Weekamp et al, 2005). Hyperopia is another specific feature of NOG mutations, but high observation rate was found only in SABTT.…”

“…The causes of SABTT phenotype were suggested to be associated with truncated or severe conformational change in the NOG protein at the finger 2 structure, which resulted in loss of C-terminal domain function or haploinsufficiency through mutated-protein mediated decay (Weekamp et al, 2005;Brown et al, 2002). Among previous SABTT cases (Table 1), seven cases lost the finger 2 structure by frameshift mutation or conforming truncated protein, and one case with changed conformation of the finger 2 structure associated with p.L203P (one amino acid change from leucine to proline), which resulted in a severely mutated protein structure due to proline's fixed structural angle (Weekamp et al, 2005).…”

“…Among previous SABTT cases (Table 1), seven cases lost the finger 2 structure by frameshift mutation or conforming truncated protein, and one case with changed conformation of the finger 2 structure associated with p.L203P (one amino acid change from leucine to proline), which resulted in a severely mutated protein structure due to proline's fixed structural angle (Weekamp et al, 2005).…”

Molecular and clinical delineation of the 17q22 microdeletion phenotype

“…[25][26][27][28][29] Two previously reported 17q22 microdeletion, patients were intellectually disabled. 7,8 All patients in our study, including patient 6, have intellectual disability and deletions of NOG and C17ORF67.…”