The disease associated to an ADGRB3 pathogenic mutation is an ultrarare disorder, it is so far fully clinically characterized in a single family. Its full clinical picture is shown in case of biallelic mutation, consequently its inheritance can be considered as autosomal recessive. However, heterozygotes are not healthy, but they show a milder phenotype. Main clinical features in the homozygotes are cerebellar ataxia, intellectual disability, memory difficulties, and affective emotional issues, such as anxiety and mood instability. The comorbidity of seizures in childhood may lead to a more severe phenotype, including prominent psychiatric symptoms, such as inappropriate laughing, social closure, and hallucinations, and severe intellectual disability. The heterozygotes show a milder phenotype, ranging from normal cognitive function to hallucinations, mood alterations, aggression, psychomotor agitation, insomnia, anxious/depressive disorder, and restless legs syndrome. What should be kept in mind is that the above-mentioned phenotypic overview derives from two homozygous siblings, and two heterozygous parents. The presumable report of additional patients will certainly shed more light on the phenotypic range.
ADGRB3