RAB18 Deficiency

Background and History: 

This syndrome was described by Mette Warburg and coworkers in 1993 as the Micro syndrome because many components of the eye are abnormally small. Since then this syndrome has been divided into at least 4 subtypes based on the specific mutation involved.

Clinical Correlations: 

Infants are sometimes born with a small head (microcephaly) and MRI studies reveal that many brain structures are abnormally small or deformed.  Psychomotor retardation and developmental delays are common and a few have seizures.  There is also an excess of facial hair and the base of the nose is unusually broad.  The ears seem to be rotated toward the back of the skull while the lower jaw appears to be abnormally small.  Newborns may seem unusually limp but spasticity in the limbs often develops later.  Male genitalia are abnormally small and short stature is common.

The eyeballs, cornea, and the openings between the eyelids are often small.  The optic nerves (that connect the eye to the brain) and the retinas usually have evidence of malfunction suggesting that vision is likely to be subnormal.  Cataracts are common while pupils often are small and do not react normally to light.


This is an autosomal recessive disorder in which mutations in both members of a specfic pair of genes are required for the disorder to be expressed.  Two normal appearing parents who each carry a mutation in single dose can expect that on average one out of four of their children will inherit this condition. 

Mutations in at least 4 different genes have been associated with this condition.

Diagnosis and Prognosis: 

The diagnosis can be suspected at birth based on the appearance of a child.  An MRI of the brain can help confirm the diagnosis.  It is important to obtain a full ophthalmologic examination to determine the nature of the eye abnormalities and a neurologist should do a complete examination of the nervous system.  There is no known treatment beyond supportive care but there is a wide range in the clinical characteristics among patients.  Warburg micro syndrome is a rare condition and more cases are needed to document the full nature of signs and symptoms. 

Additional Information
Autosomal recessive