Clinical features
Mutations in the TMEM231 gene may cause one of two disorders: Meckel-Gruber syndrome or Joubert syndrome. Meckel-Gruber syndrome is caused by a homozygous mutation in the TMEM231 gene (an identical mutation of both the paternal and maternal alleles or copies of the gene). On the other hand, Joubert syndrome is caused by a compound heterozygous mutation in the TMEM231 gene (two different mutations affecting the paternal and maternal alleles or copies of the gene).
Meckel-Gruber syndrome is more severe, usually presenting with oligohydramnios (deficiency of amniotic fluid during pregnancy), occipital encephalocele (sac-like protrusion of the brain and the membranes that cover it through an opening at the back of the skull), polydactyly (extra fingers and toes), and polycystic kidneys (fluid-filled cysts in the kidneys that may compromise kidney function). This disorder is usually lethal during the foetal stage or early infancy.
Joubert syndrome usually presents with oculomotor apraxia (absence of voluntary and controlled eye movement), a brain abnormality called molar tooth sign seen on MRI imaging, and developmental delay. Other features may include polydactyly and kidney cysts.
Prevalence
The prevalence of TMEM231-related conditions cannot be accurately estimated due to the limited number of cases reported.
Inheritance
Mutations of this gene can be passed on to the next generation in an autosomal recessive manner. This means that if both parents carry a mutation involving this gene (usually without displaying the disease), there is a greater chance that their children are going to inherit the mutations from both parents and display the disease. This is especially important to consider in consanguineous marriage, where the chance of both parents having the same mutation and passing it is greater.