DOORS syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 9, 2017
StartDiseasesDOORS syndrome

DOOR syndrome is a genetic disorder. DOORS is an acronym for deafness, onychodystrophy, osteodystrophy, retardation, and S for seizures. Onychodystrophy means deformed nails, while osteodystrophy means deformed bones. People born with DOORS syndrome may have some or all of these signs. It is also referred to as DOORS syndrome.

Contents

Definition & Facts

Some features of DOORS syndrome occur before birth. There is an unusual volume of amniotic fluid, or polyhydramnios during the pregnancy and an increased nuchal fold. The nuchal fold scan measures how much amniotic fluid has collected at the back of the neck of the fetus. An increase indicates an abnormality.

DOORS syndrome is an extremely rare condition, and as of 2017 there have only been 50 known cases of it. It affects boys and girls equally. Medical experts do not know how prevalent it is.

Symptoms & Complaints

Most signs of DOORS syndrome are seen at birth. The child is deaf, though this might not be noticeable until they are older. The problem involves the child’s inner ear, which can’t send electrical signals to the hearing centers in the brain.

DOORS syndrome babies may lack nails or have short nails. The texture, color and shape of the nails may be abnormal. Their fingers and toes may be unusually short because the growth of the bones in the digits is abnormal, and they may have odd fingerprints where every finger has an arch pattern. Some children have an extra bone in the big toe or thumb, which makes the thumb look like another finger. This is called triphalangeal thumb

Children with DOORS syndrome have intellectual disabilities and developmental delays that may be mild or severe. The child’s deafness often contributes to their intellectual disability, but DOORS syndrome children are also late in sitting, crawling, and walking as well as speech.

They may have visual problems such as cataracts, severe near-sightedness, detached retinas, or crossed eyes (strabismus). Some suffer from peripheral neuropathy, or problems with how the nerves send sensory signals from the hands and feet to the brain. This problem makes it hard for the child to feel pain.

Other symptoms are an unusually wide nose, a smaller than normal head (microcephaly), and wide ridges in both the upper and lower jaw. The roof of the mouth can be unusually high or narrow, and there might be a short membrane between their tongue and the bottom of their mouth. Sometimes the teeth are very small and their enamel is thin and insufficient. There may be congenital heart defects or defects in the urinary tract.

DOORS syndrome patients are commonly afflicted with seizures. These begin before the child is a year old and present as grand mal seizures. Some babies begin to have seizures when they are six weeks old. These seizures can exacerbate a child's intellectual disability.

These seizures can progress to a dangerous condition called status epilepticus, where the child has fallen unconscious, and the seizures are continuous. Status epilepticus is a medical emergency, and the child must be seen by a health professional as soon as possible.

Some DOORS syndrome patients have high amounts of an acid called 2-oxoglutarate in their blood plasma and their urine. Doctors do not know why this is, but elevated levels of this acid may indicate a more severe type of DOORS syndrome. Other patients have low levels of thyroid hormone or hypothyroidism.

Causes

Scientists know that DOORS syndrome is caused by genetic factors and that a copy of the mutated gene needs to be inherited from both parents. Researchers point to the TBC1D24 gene as a cause of DOORS syndrome. Doctors do not know the exact function of the protein this gene produces, though it is active in many organs in the body, especially in the brain and the specialized, hair-like cilia found in the patient’s inner ear. These cilia, called stereocilia, respond to sound waves and help the person hear.

There is speculation that the TBC1D24 protein supports the movement of vesicles inside cells. These vesicles carry proteins around the cells. The TBC1D24 protein may help cells fight off damage from free radical molecules. The mutation in the TBC1D24 gene is thought to destroy the protein, but researchers do not know why this leads to DOORS syndrome. However, some DOOR syndrome patients do not have the TBC1D24 mutation.

Another gene called SMARCB1 is also implicated in DOORS syndrome. Sometimes, the parents of a DOORS syndrome patient are closely related to one another and have a higher chance of carrying the genes for this rare disorder.

Diagnosis & Tests

Doctors suspect DOORS syndrome by noting the baby’s abnormal bone growth, nails, and fingerprints. Imaging tests such as X-rays can show extra bones in the thumb or the big toe and the underdeveloped bones in the other fingers and toes. These signs tell the doctor that the child should be tested for deafness.

Children who have seizures can be diagnosed through EEG, or electroencephalography, computed tomography (CT) scans, or magnetic resonance imaging (MRI) scans. The EEG picks up the electrical signals from the brain, while the other scans show the structure of the brain tissue.

Treatment & Therapy

Treatment of DOORS syndrome is tailored to the symptoms of each patient and requires the help of many specialists. These include pediatricians, neurologists, physical therapists, social workers, audiologists and surgeons. It is important to treat the child’s deafness to improve their ability to speak and communicate overall.

Physicians prescribe medications for seizures, though these medications may not always work, and other professionals help the child and their family cope with developmental and intellectual disabilities. DOORS syndrome babies who have trouble feeding may be fed through a feeding tube.

Prevention & Prophylaxis

There is no way to prevent DOORS syndrome as of 2017. Prospective parents who possess the mutated gene can be provided with genetic counseling. There are too few people with the disorder for researchers to establish a firm prognosis for the long term.