Clinical Guidance

Pathogenic variants associated with FLNA-OPD spectrum disorders are predicted to maintain the translational reading frame of FLNA and to produce full-length protein. These variants are clustered in discrete regions of the gene. Genotype-phenotype correlation is strong . The clinical presentation and position of the FLNA pathogenic variant can often broadly predict the phenotype. For example, MNS due to recurrent variants in exon 22 of FLNA are invariably associated with prenatal lethality in males; pathogenic variants in FLNA exons 2-4, associated with an FMD phenotype in females, are consistent with male survival.

Source: GeneReviews — "FLNA-Related Otopalatodigital Spectrum Disorders"

Penetrance

Penetrance in males with an FLNA pathogenic variant leading to an FLNA-OPD spectrum disorder is complete. Some obligate heterozygote females with FLNA pathogenic variants leading to FLNA-OPD1 have a normal clinical appearance. The proportion of heterozygous females with radiographic features of FLNA-OPD1 is unknown.

Source: GeneReviews — "FLNA-Related Otopalatodigital Spectrum Disorders"

Diagnostic Criteria

The FLNA-related otopalatodigital (FLNA-OPD) spectrum disorders, a heterogeneous group of disorders characterized primarily by a skeletal dysplasia of variable severity, include the following:

• Otopalatodigital syndrome type 1 (FLNA-OPD1)

• Otopalatodigital syndrome type 2 (FLNA-OPD2)

• Frontometaphyseal dysplasia type 1 (FLNA-FMD)

• Melnick-Needles syndrome (FLNA-MNS)

• Terminal osseous dysplasia (FLNA-TOD)

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care . No consensus clinical diagnostic criteria for FLNA-OPD spectrum disorders have been published.

Suggestive Findings

FLNA-OPD spectrum disorders should be suspected in an individual with the following clinical features , radiographic feat...

Source: GeneReviews — "FLNA-Related Otopalatodigital Spectrum Disorders"

Differential Diagnosis

Skeletal dysplasias of interest in the differential diagnosis of FLNA-related otopalatodigital (FLNA-OPD) spectrum disorders are listed in . Table 5. Genes of Interest in the Differential Diagnosis of FLNA-Related Otopalatodigital Spectrum Disorders

Management Guidelines

No clinical practice guidelines for FLNA-related otopalatodigital (FLNA-OPD) spectrum disorders have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with an FLNA-OPD spectrum disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 6.

FLNA-Related Otopalatodigital Spectrum Disorders: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Musculoskeletal

| • Clinical exam of extremities, joints, spine

• Complete skeletal survey w/scoliosis series if indicated

| To evaluate for contractures, joint subluxations/dislocations, scoliosis

Craniofacial

| Clinical exam for facial or skull growth asymmetry | To evaluate for craniosynostosis

Audiology eval | To evaluate for conduction sensorineural hearing loss

Clinical exam of palate referral to ENT as necessary | To evaluate for cleft palate subglottic stenosis

Respiratory

| Referral to pulmonologist if indicated | To evaluate for respiratory complications assoc w/thoracic hypoplasia

Cardiac

| Echocardiogram | To evaluate for septal defects, right ventricular outflow tract obstructive lesions, cardiomyopathy

Dental

| Dental eval | To evaluate for hypodontia, oligodontia

Genitourinary

| Renal tract ultrasound exam | To...

Source: GeneReviews — "FLNA-Related Otopalatodigital Spectrum Disorders"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "FLNA-Related Otopalatodigital Spectrum Disorders"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 8. FLNA-Related Otopalatodigital Spectrum Disorders: Recommended Surveillance

Source: GeneReviews — "FLNA-Related Otopalatodigital Spectrum Disorders"