The TBC1D24 Mutation
What we know:
Mutations in the TBC1D24 gene can cause individuals to have epilepsy, deafness, shortened nails, fingers, and toes. Mutations in this gene may also cause hypotonia (low muscle tone), and developmental delays in babies and toddlers. If delays persist into teenage years and adulthood, then intellectual disabilities may be present.
There are cases in which only some features of the TBC1D24 gene mutation are present and some in which all features are present. There is a wide spectrum of severity in which these features will fall, and this severity varies based on each individual person.
When all features are present it is commonly referred to as DOORS syndrome; DOOR (deafness, onychodystrophy, osteodystrophy, and mental retardation). This syndrome is an inherited genetic disease, and is characterized by mental retardation, sensorineural deafness, abnormal nails, phalanges of the hands and feet, and variable
seizures.
In some cases, single dominant mutations can cause deafness, meaning only one copy needs to be mutated. The deafness, when present, has been addressed effectively by cochlear implants.
Generally, both inherited copies of TBC1D24 gene (the one one from the mother and the one from the father) need to have a mutation for an individual to be affected.
In any individual with TBC1D24 mutation, there can be abnormal facial, oral, and body movements in addition to the seizures. These abnormal movements may not correspond to seizure activity on an EEG. In some individuals, seizures are refractory to treatment, meaning that they are very difficult to treat with 1 or 2 anti-epileptic medications. Frequent medication changes and adjustments are a common occurrence. In some affected individuals, the neurological disease progresses/worsens. At the moment, it is not possible to predict which exact TBC1D24 mutations will cause a progression of the disease. Currently, observing a child over time is the only information available to us regarding progression of disease.
Unfortunately the things we don't know far outweighs the information we have to date. One of main goals is to change that, to support and fund research into this mutation and what that means for those affected.
Do you think your child may have a TBC1D24 mutation?
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Whole Exome Sequencing is a DNA blood test used to diagnose a TBC1D24 Mutation and other rare genetic disorders. Talk to your child’s geneticist to see if this is the right test for your family.
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Find out more here.
Common Symptoms
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Hypotonia
Low muscle tone; some babies and children have low tone all the time, some have low tone only when unwell.
Dystonia
Involuntary muscle contractions- twisting and repetitive movements.
Screaming Seizure
Babies often bring knees to chest and simultaneously scream. Their eyes may deviate, baby may turn red and may be stiff during these episodes. This has often been misdiagnosed by pediatricians as
“baby learning to poop.”
Eye roll/head movement
Some babies have displayed abnormal eye movements in conjunction with abnormal head movements. These movements occur together but are not synchronized and could look like baby has lost control of their eyes. May be misdiagnosed as reflux related.
Hard of Hearing or Deafness
Baby may fail hearing screens at birth and subsequent tests.
Blindness/ Cortical Visual Impairment
Some babies may not meet visual milestones such as “tracking” (appropriately following objects with eyes)
Global developmental delay
Babies and children may not reach typical milestones on time.
Ataxia
Impaired balance and coordination. Children or adults who are able to walk may do so with a “wide gait.”
Seizures
Various types, may be resistant to medications.
Tremors and Twitches
Can be considered part of a possible movement disorder, as some may not correlate with EEG seizure activity. Twitches/Tremors can start in the hands, feet, lips, mouth, and eyes. These can sometimes be extinguished by sleep or medication, otherwise may progress into seizures.
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DOORS (extension of Tbc1d24, that comes with it’s own set of symptoms)
D: deafness
O: onychodystrophy (Short or absent nails)
O: osteodystrophy ( developmental delay and intellectual disability)
R: mental retardation ( a term no longer used)
S: seizures