Penetrance

Penetrance of TBC1D24-related disorders appears to be high, at least for the conditions known to be inherited in an autosomal recessive pattern, but variable expressivity, even within the same phenotype, has been described. Penetrance is not different between males and females. DFNA usually manifests in the third decade of life.

Source: GeneReviews — "TBC1D24-Related Disorders"

Diagnostic Criteria

TBC1D24-related disorders comprise a continuum of distinct phenotypes:

• DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures)

• Familial infantile myoclonic epilepsy (FIME)

• Progressive myoclonic epilepsy (PME)

• Rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp (EPRPDC)

• Developmental and epileptic encephalopathy (DEE), including epilepsy of infancy with migrating focal seizures (EIMFS)

• Autosomal recessive nonsyndromic hearing loss (DFNB)

• Autosomal dominant nonsyndromic hearing loss (DFNA)

Suggestive Findings

A TBC1D24-related disorder should be suspected in individuals with the following clinical features, which have been reported in several phenotypes that comprise a phenotypic continuum (information on additional features is pro...

Source: GeneReviews — "TBC1D24-Related Disorders"

Differential Diagnosis

DOORS Syndrome Table 4. Genetic Disorders in the Differential Diagnosis of DOORS Syndrome

Management Guidelines

No clinical practice guidelines for TBC1D24-related disorders have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with a TBC1D24-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 6.

TBC1D24-Related Disorders: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Neurologic

| Neurologic eval to assess for risk of epilepsy | • EEG to assess overall degree types of seizures

• Baseline brain MRI

Clinical neurologic eval | • Neurologic exam to assess if a movement disorder or other neurologic involvement (e.g., dysarthria nystagmus, peripheral neuropathy) is present

• Head circumference to establish presence of microcephaly assess whether other cranial abnormalities are present

Neuropsychological eval to assess for neurodevelopmental delay /or degree of ID |

Audiologic

| Audiologic eval for hearing loss |

Ophthalmologic

| Ophthalmology eval to assess visual function |

Cardiac

| Cardiac eval to assess for congenital heart defects arrhythmia | Consider echocardiogram EKG

Renal

| Nephrology eval to assess for renal urinary tract anomalies (e.g., hydronephrosis, nephrocalcinosis) | Consider renal ultrasound

Dental

| Dental eval to assess for dental anomalies (e.g., delayed eruption, wide spacing, abnormal shape, size, number) |

Endocrine

| Endocrine eval for thyroid function |

Orthopedic

| Orthopedic eval to as...

Source: GeneReviews — "TBC1D24-Related Disorders"

Clinical Guidance

Individuals with a heterozygous TBC1D24 pathogenic variant causing autosomal dominant deafness (DFNA) should avoid excessive ambient noise, as it may exacerbate hearing loss.

Source: GeneReviews — "TBC1D24-Related 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. TBC1D24-Related Disorders: Recommended Surveillance

Source: GeneReviews — "TBC1D24-Related Disorders"