Most of individuals mutated in TBC1D20 are affected by Warburg micro syndrome, although a single family has been described with two sibs presenting with a milder phenotype more compatible with Martsolf syndrome. Individuals mutated in TBC1D20 generally have severe intellectual disability, with language acquisition being largely absent. In patients with Martsolf syndrome language is delayed, but it is acquired. Individuals with Warburg syndrome have severe motor dysfunction, are hypotonic as infants and do not have head control. Due to development of severe spasticity involving initially the lower limbs and subsequently the all four limbs (spastic quadriplegia), they are unable to walk. The progression of the disease can lead to respiratory dysfunction.
In Martsolf syndrome these symptoms are milder. Hypotonia is present in neonates but spasticity progresses more slowly and patients are usually able to walk with support. Both patients with Warburg micro syndrome and those with Martsolf syndrome have hypogenitalism, which in males can manifest with micropenis and/or undescended testicles. Typical ocular abnormalities in these patients are congenital cataracts, microphthalmia, microcornea, small pupils. Patients with TBC1D20 mutations can develop glaucoma. Despite cataract surgery, patients' vision remains poor due to progressive optic atrophy. Also visual impairment is less severe in Martsolf syndrome than in Warburg micro syndrome. Other neurological symptoms include microcephaly, which is not present at birth but develops later, epilepsy, which may or may not be present, and feeding difficulties, such as gastroesophageal reflux and dysphagia. Patients usually require the implantation of a gastrostomy tube to improve nutrition. Typical facial abnormalities are generally recognizable as deep-set eyes, broad nasal bridge, a narrow mouth, and large anteverted ears. MRI analysis reveals in these patients severe brain anomalies.