What are the other Names for this Condition? (Also known as/Synonyms)

• Autosomal Recessive Deafness-Onychodystrophy Syndrome
• Deafness-Onychodystrophy-Osteodystrophy-Intellectual Disability Syndrome
• DOORS Syndrome

What is Digitorenocerebral Syndrome? (Definition/Background Information)

• Digitorenocerebral Syndrome, also known as DOORS Syndrome, is a multiple congenital anomalies-intellectual disability syndrome characterized by sensorineural hearing loss (deafness), onychodystrophy, osteodystrophy, mild to profound intellectual disability, and seizures
• The disorder is caused by mutations in the TBC1D24 gene (16p13.3) encoding a protein involved in the regulation of membrane trafficking
• Digitorenocerebral Syndrome is transmitted in an autosomal recessive manner

(Source: DOORS Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Digitorenocerebral Syndrome? (Age and Sex Distribution)

• Digitorenocerebral Syndrome is a very rare congenital disorder that is seen at an incidence rate of less than 1 in 1 million 
• The presentation of symptoms may occur at birth
• Both males and females may be affected

What are the Risk Factors for Digitorenocerebral Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Digitorenocerebral Syndrome can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Digitorenocerebral Syndrome? (Etiology)

• Digitorenocerebral Syndrome is caused by mutations in the TBC1D24 gene (16p13.3) encoding a protein involved in the regulation of membrane trafficking 
• The disorder is inherited in an autosomal recessive manner

(Source: DOORS syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected)

What are the Signs and Symptoms of Digitorenocerebral Syndrome?

The signs and symptoms of Digitorenocerebral Syndrome may vary in type and severity among the affected individuals. The signs and symptoms may include:

• Profound sensorineural deafness 
• Small or absent nails
• Short distal phalanges of hands and feet.  
• Long, finger-like thumbs 
• Facial abnormalities, such as
• Broad nasal bridge 
• Anteverted nares
• Long philtrum
• Thin upper vermilion 
• Low set ears 
• Craniosynostosis (abnormal shape of skull)
• Optic atrophy leading to the following:
• Blindness
• Retinal detachment
• Strabismus
• Nystagmus, 
• High myopia 
• Cataracts 
• Developmental delay, which can range from mild delays in early motor milestones to generalized and lifelong hypotonia 
• Seizures (often generalized tonic-clonic) 
• Behavioral problems
• Dental malformations (hypoplastic enamel, abnormal size of teeth) 
• Internal organ malformations (congenital heart defects, unilateral renal agenesis, cystic kidney, duplicated kidney) 

(Source: DOORS syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Digitorenocerebral Syndrome Diagnosed?

Digitorenocerebral Syndrome is diagnosed on the basis of the following information:

• Patients are checked for each of the 5 major characteristics by conducting X-rays of the hands and feet, a brain stem auditory evoked response test for hearing loss, and an electroencephalogram (EEG)
• Elevated levels of 2-oxoglutaric acid in the urine and plasma have repeatedly been reported in both patients with and without aTBC1D24mutation. If present, Digitorenocerebral Syndrome (DOORS syndrome) is suspected, although elevated levels can also occur in other disorders
• Molecular genetic testing identifying aTBC1D24mutation may confirm the diagnosis but absence of the mutation does not mean a diagnosis of Digitorenocerebral Syndrome (DOORS syndrome) is incorrect

(Source: DOORS syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Digitorenocerebral Syndrome?

The complications of Digitorenocerebral Syndrome may include:

• Seizure-related complications such as:
  • Trauma/injury: Seizures can lead to fall injuries affecting the head, or cause bone fractures
  • Status epilepticus is a seizure that lasts longer than normal. A time duration of 30-60 minutes is generally considered a minimum requirement for usage of the term Status Epilepticus, to describe the condition. It is considered a serious life-threatening condition and is a medical emergency
  • Psychological issues; especially depression, anxiety, and in some cases suicidal tendencies are noted
  • Complications during pregnancy: There is a potential for reduction in fertility. Certain anti-epileptic medications increase the risk of birth defects
  • Sudden unexplained deaths with Epilepsy: This phenomenon is not well understood, but could be related to disturbances in the heart's rhythm or due to breathing problems
• Hearing and vision loss
• A sense of isolation

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Digitorenocerebral Syndrome Treated?

There is no cure for Digitorenocerebral Syndrome, since it is a genetic condition. The treatment is supportive and may involve:

• Long-term management involves regular ophthalmologic and hearing tests as well as neurological exams such as EEGs 
• A feeding tube may be necessary in infants with feeding difficulties 
• Antiepileptic medication may be used to prevent or decrease the frequency of seizures but is not always effective

(Source: DOORS syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Digitorenocerebral Syndrome be Prevented?

• Digitorenocerebral Syndrome may not be preventable, since it is a genetic disorder
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Digitorenocerebral Syndrome? (Outcomes/Resolutions)

• Life expectancy in Digitorenocerebral Syndrome is usually normal 
• Intellectual disability is lifelong, but there is no known correlation between clinical manifestations and cognition 
• The number of known adults with this disorder is at present too small to predict the long term prognosis

(Source: DOORS syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Digitorenocerebral Syndrome:

Digitorenocerebral Syndrome is also known by the following names: 

• Deafness-Onychodystrophy-Osteodystrophy-Intellectual Disability-Seizures Syndrome
• Deafness-Onychoosteodystrophy-Intellectual Disability Syndrome
• DRC Syndrome

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/