Clinical Guidance

RAB18 deficiency results from biallelic pathogenic variants in RAB3GAP1, RAB3GAP2, RAB18, or TBC1D20 [, , , , ]. Biallelic loss-of-function variants in any one of these genes cause Warburg micro syndrome, which corresponds to the severe end of the phenotypic spectrum. Pathogenic variants that diminish but do not completely nullify gene expression or function can cause or contribute to Martsolf syndrome, which corresponds to the milder end of the phenotypic spectrum. Warburg micro syndrome comprises the majority (98/102 families) of molecularly confirmed RAB18 deficiency reported [, , , , , , , , , , , , , , , , , , , , ].

Source: GeneReviews — "RAB18 Deficiency"

Diagnostic Criteria

Suggestive Findings

RAB18 deficiency should be suspected in individuals with the following clinical and neuroimaging findings. Note: Findings indicated with an * are the basis of the diagnosis when molecular genetic testing either has not been performed or has not revealed biallelic pathogenic variants in one of the four known genes.

Clinical Findings

Ophthalmologic

Source: GeneReviews — "RAB18 Deficiency"

Differential Diagnosis

Array CGH may be useful in identifying pathogenic copy number variants associated with clinical findings similar to those in RAB18 deficiency . Similarly, TORCH screening may useful in determining whether prenatal infection is a potential cause of the clinical findings . Note that in RAB18 deficiency, prenatal onset of cataracts appears to be a consistent feature, a finding in contrast to other inherited conditions in which cataracts are a more variable manifestation or can arise postnatally. Differential diagnosis therefore includes some other syndromes with congenital cataracts. Table 2. Disorders to Consider in the Differential Diagnosis of RAB18 Deficiency

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with RAB18 deficiency, the evaluations (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis of RAB18 Deficiency

Source: GeneReviews — "RAB18 Deficiency"

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 — "RAB18 Deficiency"

Surveillance Guidelines

No formal surveillance guidelines exist for RAB18 deficiency. Suggested surveillance includes routine follow up with

• An ophthalmologist

• A neurologist

• A developmental specialist, such as a developmental pediatrician

• A feeding team and nutritionist

• An endocrinologist, especially in infancy to assess degree of hypogonadism and at the age that puberty typically would occur

• Hearing tests

Source: GeneReviews — "RAB18 Deficiency"