Teunissen-Cremers syndrome: a clinical, surgical, and genetic report.
OBJECTIVE
To describe clinical and radiologic features, results of ear surgery, and genetic analysis in three families with Teunissen-Cremers syndrome.


METHODS
Case series.


METHODS
Tertiary referral center.


BACKGROUND
The NOG gene encodes the protein noggin, which has antagonist action in osteogenesis. Malformation of bones and joints may result from defects in noggin. Teunissen-Cremers syndrome is caused by mutations in the NOG gene. Two mutations in this gene were reported previously. The proximal symphalangism-hearing impairment syndrome, also caused by mutations in the NOG gene, is characterized by proximal symphalangism, conductive hearing loss, and occasionally synostoses.


METHODS
We examined nine affected members of three Dutch families. Reconstructive middle ear surgery was performed in five patients (nine ears), and we sequenced the NOG gene in these families.


RESULTS
Affected members had conductive hearing impairment, hyperopia, and broad thumbs and first toes with brachytelephalangia. Surgery manifested stapes ankylosis with additional incudal fixation frequently in the fossa incudis. Air-bone gaps decreased to less than 10 dB in six ears. Genetic analysis revealed three new mutations in the NOG gene.


CONCLUSIONS
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.
Weekamp
H H
HH
Departments of Otorhinolaryngology-Head and Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Kremer
H
H
Hoefsloot
L H
LH
Kuijpers-Jagtman
A M
AM
Cruysberg
J R M
JR
Cremers
C W R J
CW
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000844:Ankylosis / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D001301:Audiometry, Pure-Tone; D001844:Bone Conduction / Q000235:genetics / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002352:Carrier Proteins; D002508:Cephalometry; D002648:Child; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D005532:Foot Deformities, Congenital / Q000175:diagnosis / Q000235:genetics; D005838:Genotype; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics; D006314:Hearing Loss, Conductive / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006801:Humans; D006956:Hyperopia / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009998:Ossicular Prosthesis; D010641:Phenotype; D012022:Reflex, Acoustic / Q000235:genetics / Q000502:physiology; D013199:Stapes / Q000002:abnormalities*; D013200:Stapes Mobilization; D013576:Syndactyly / Q000175:diagnosis / Q000235:genetics; D013577:Syndrome; D013580:Synostosis / Q000175:diagnosis / Q000235:genetics; D013933:Thumb / Q000002:abnormalities; D014057:Tomography, X-Ray Computed; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein