FLNA-related disorders, sequencing
Otopalatodigital Spectrum Disorders
|Clinical info||There are several different phenotypes that have been associated with mutations in the FLNAgene.
FLNA mutations have been reported for the otopalatodigital spectrum disorders which include OPD type 1 & type 2 (OPD1 & OPD2), frontometaphyseal dysplasia (FMD) and Melnick-Needles syndrome (MNS). Males are usually more severely affected than females, but females present with variable expressivity. While the primary manifestation is skeletal dysplasia, males may also have a range of congenital anomalies. The most severe types are lethal in males. Normal intelligence is common except for in males with OPD2.
Mutations in the FLNA gene have also been associated with X-linked periventricular heterotopia. This disorder is generally lethal in males and affected females present mid-teens with seizures. This is a neuronal migration disorder in which brain imaging should be used to help establish the diagnosis. Affected females may also have cardiovascular findings, strabismus, psychiatric disorders or learning problems.
There is also an X-linked periventricular heterotopia, Ehlers-Danlos variant. In addition to the heterotopias, these patients have hyperflexible joints, and aortic dilatation or aneurysms.
FLNA mutations have also been reported in cases of X-linked cardiac valvular dysplasia in males characterized by mitral and/or aortic valve regurgitation. Female carriers are asymptomatic.
X-linked chronic idiopathic neuronal intestinal pseudoobstruction is a result of abnormal gastrointestinal motility with recurrent symptoms. All reported affected individuals have been male.
|Indications||Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutation within a family to allow for carrier testing and prenatal diagnosis.|
|Associated Tests||The FLNA gene is also part of the XLID gene panel.|
|Detection||Otopalatodigital spectrum disorders have variable detection depending on the subtype. There are genotype-phenotype correlations with these disorders and specific regions of the gene. Sequencing will detect a mutation in 43% of OPD1, 69% of ODP2, 57% of FMD and almost all patients with MNS.
Sequencing of FLNA will detect a mutation in 98-100% of females with periventricular heterotopia when there is a family history, but only 26% of females will have a mutation when there is no family history.
There are not clear clinical detection rates for the other, rarer, phenotypes associated with mutations in FLNA.
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.|
|Turnaround time||6 weeks|
|Prenatal testing||Prenatal diagnosis is available if the familial mutation is known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.|
|CPT Codes||Unknown mutation: 81479
Known mutation: 81404
Deletion/Duplication Analysis: 81229
$2200 for sequencing
$700 for deletion/duplication analysis
Prenatal diagnosis for known mutation is $1000. Please contact the laboratory for more information.
Molecular Diagnostic Lab
The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.