Deafness, Congenital, with Inner Ear Agenesis, Microtia, and Microdontia via the FGF3 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
2219 FGF3$490.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

No large-scale studies have been conducted on sequence variants in the FGF3 gene, thus its clinical sensitivity is unclear. Of the seven available reports on pathogenic sequence variants in the FGF3 gene, two were case reports (Dill et al. 2011; Singh et al. 2014), whereas five were small-scale family studies consisting of 1 to 3 families, with each family having 2 to 21 affected members (Tekin et al. 2007; Alsmadi et al. 2009; Riazuddin et al. 2011; Sensi et al. 2011; Schaefer et al. 2014).

See More

See Less

Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 FGF3$990.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

Total Price









Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features

Congenital deafness with inner ear agenesis, microtia, and microdontia, also known as deafness with labyrinthine aplasia, microtia, and microdontia (LAMM) or Michel aplasia, microdontia, and malformation of the inner ear, is characterized by profound congenital sensorineural hearing loss combined with slightly smaller ears (type I microtia) and smaller teeth (microdontia) that are often widely spaced apart (Alsmadi et al. 2009). The ears of LAMM patients generally show shortened auricles, particularly at the crura of the antihelix. Computed tomography imaging of the temporal bones of LAMM patients often show complete bilateral absence of structures of the inner ear, which include the cochlea, vestibule, and semicircular canals. However, the middle ear of LAMM patients remains intact. Although physical examination of individuals with LAMM generates normal results, they are generally delayed in motor development during infancy, mainly due to impaired balance that is caused by the absence of structures of the inner ear. Despite their hearing impairment, LAMM patients have normal cognitive abilities and do not experience difficulties in writing or reading. Certain patients with LAMM may present less prominent dental as well as external ear features, yet their inner ear often present structural abnormalities (Riazuddin et al. 2011). The symptoms of small ears and teeth are also observed in patients with lacrimoauriculodentodigital (LADD) syndrome (Mathrawala and Hegde 2011).


Congenital deafness with inner ear agenesis, microtia, and microdontia is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the fibroblast growth factor 3 (FGF3) gene, which is located in chromosome 11q13.3 (Casey et al. 1986). The FGF3 gene consists of 3 coding exons that encode a 239-amino acid oncoprotein, which is mainly expressed in the rhombencephalon during fetal development when inner ear induction occurs, acting as a signal for the formation of the otic vesicle (Frenz et al. 2010). Disease-causing sequence variants in the FGF3 gene have also been implicated in three other disorders, namely, otodental syndrome (characterized by grossly enlarged molar teeth and high-frequency sensorineural hearing loss), craniosynostosis (a birth defect that involves premature fusion of the skull bones of an infant, thereby changing the growth pattern of the skull), and odontoma-dysphagia syndrome (presents with grossly enlarged, clustered teeth, slight facial abnormalities, and difficulty to swallow) (Gregory-Evans et al. 2007; Grillo et al. 2014). To date, a total of about 20 pathogenic FGF3 sequence variants have been reported, which include 10 missense/nonsense and 4 small deletions that cause LAMM, 3 gross deletions that cause otodental syndrome, and 2 gross insertions that cause craniosynostosis, and 1 gross insertion that causes odontoma-dysphagia (Human Gene Mutation Database).

Testing Strategy

Testing is accomplished by amplifying the coding exons of the FGF3 gene and ~10 bp of adjacent noncoding sequence, then determining the nucleotide sequence using standard dideoxy Sanger sequencing methods and a capillary electrophoresis instrument. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

Indications for Test

The ideal FGF3 test candidates are individuals who present with congenital, profound, autosomal recessive nonsyndromic hearing loss with complete absence of the inner ear, microtia, and microdontia.


Official Gene Symbol OMIM ID
FGF3 164950
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Alsmadi O. et al. 2009. European Journal of Human Genetics : Ejhg. 17: 14-21. PubMed ID: 18701883
  • Casey G. et al. 1986. Molecular and Cellular Biology. 6: 502-10. PubMed ID: 3023852
  • Dill P. et al. 2011. Molecular Genetics and Metabolism. 104: 362-8. PubMed ID: 21752681
  • Frenz DA. et al. 2010. American Journal of Medical Genetics. Part A. 152A: 2947-61. PubMed ID: 21108385
  • Gregory-Evans CY. et al. 2007. Human Molecular Genetics. 16: 2482-93. PubMed ID: 17656375
  • Grillo L. et al. 2014. Gene. 534: 435-9. PubMed ID: 24120895
  • Human Gene Mutation Database (Bio-base).
  • Mathrawala N.R., Hegde R.J. 2011. Journal of the Indian Society of Pedodontics and Preventive Dentistry. 29: 168-70. PubMed ID: 21911959
  • Riazuddin S. et al. 2011. Bmc Medical Genetics. 12: 21. PubMed ID: 21306635
  • Sensi A. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 1096-101. PubMed ID: 21480479
  • Singh A. et al. 2014. Indian Pediatrics. 51: 919-20. PubMed ID: 25432227
  • Tekin M. et al. 2007. American Journal of Human Genetics. 80: 338-44. PubMed ID: 17236138
Order Kits

Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
loading Loading... ×