Thanatophoric Dysplasia

By | June 10, 2022

Thanatophoric dysplasia is a developmental and growth disorder that is fatal. With a prevalence of 1:50,000, it is one of the rare diseases. Two types are distinguished.

What is thanatophoric dysplasia?

Thanatophoric dysplasia is a disease characterized by abnormal cartilage and bone growth. Thus, the disease is osteochondrodysplasia. There is one case of thanatophoric dysplasia per 20,000 to 50,000 births. However, the disease must be differentiated from platyspondolytic dysplasia of the Torrance type. For what does les stand for, please visit

Although the symptoms are similar, Torrance-type platyspondylotic dysplasia is a skeletal dysplasia with a typical platyspondylosis. Children born with thanatophoric dysplasia are smaller than normal. The bones are bent or shortened and the brain may be deformed. Even during pregnancy, the growth disorders are visible in the preventive medical check-ups.

A cure for the disease is not yet possible. Most children die between the 22nd week of pregnancy and the 7th day after birth. This period is also known as the perinatal period. However, there are also reports of long-term survivors who lived up to nine years.


Thanatophoric dysplasia is an inherited disorder that follows an autosomal dominant pattern of inheritance. In autosomal dominant inheritance, the specific allele is on one of the 22 autosomes. One partner allele is sufficient for the genetic information to show up in the phenotype. This means that it is sufficient if one parent passes on the defective allele. The mutation is in the FGFR3 region on chromosome 4 in section p15.3.

The area FGFR3 is the receptor 3 of the so-called fibroblast growth factor. As a result of the mutation, the bone growth of the affected children is disturbed. The cartilage cells receive growth-inhibiting signals. Disorders in the formation of bone tissue in the unborn child can already lead to malformations of the skeleton during pregnancy. The characteristic physical abnormalities develop.

Symptoms, Ailments & Signs

Children with thanatophoric dysplasia are smaller than healthy children. Compared to the body, the head appears very large. But this is because the body is too small. The supposed oversize of the head is therefore also referred to as pseudo-macrocephaly. In children with type I disease, the head has a distinct cloverleaf shape.

This means that the skull is strongly bulged on both sides in the area of ​​the temples and on the top. This shifts the ears towards the shoulders. Due to the flatness of the orbit, an exophthalmos forms. This may impair or prevent eyelid closure, which can lead to ulceration of the cornea.

This malformation is less common in type II thanatophoric dysplasia. Most children with thanatophoric dysplasia have a bulging forehead and a sunken bridge of the nose. The thorax (chest) is not properly formed and is therefore very narrow and narrow. The rib bones are too short. The long tubular bones of the body are also shortened and also bent.

This leads to micromelia. Micromelia is a congenital shortening of extremities. In type II, the femur is free of bends. The hands are too short for that. The hereditary malformation of the fingers is called short fingers or brachydactyly. Depending on the degree of severity, malformations of the brain can occur in different forms.

Diagnosis & course of disease

The first abnormalities appear in the affected children during the check-ups during pregnancy. Growth disorders can be diagnosed, and a cloverleaf skull may be visible on ultrasound. The neck also shows a pronounced transparency in the ultrasound image.

Nuchal translucency is caused by fluid buildup under the skin in the baby’s neck area. Polyhydramnios is also common. In the case of polyhydramnios, there is an above-average amount of amniotic fluid. The pregnant woman usually notices that the child hardly moves. The first suspected diagnosis is usually made by the ultrasound images.

During amniocentesis, the amniotic sac is punctured. The fetal cells are then examined to confirm the diagnosis. In thanatophoric dysplasia, the mutations in the FGFR3 gene are found on the fourth chromosome. In type I, the transmembrane receptor proteins that bind fibroblast growth factor are affected. In type II, the domains of the tyrosine kinase are affected.


Thanatophoric dysplasia is always fatal. Growth disorders and the formation of a cloverleaf skull in the embryo very often occur during pregnancy. The latter often dies in the womb. In the case of a live birth, those affected almost always develop respiratory failure due to the deformed chest, which is accompanied by acute shortness of breath and often leads to death within the first fourteen days.

Very few children reach the first year of life, a higher age than ten years has not been documented in a patient with thanatophoric dysplasia. Due to the enormous emotional burden, the parents and other family members often need psychotherapeutic care in order to process the trauma.

When should you go to the doctor?

The person affected with this disease is dependent on medical examination and treatment so that further complications can be prevented. Self-healing cannot occur here either, so treatment by a doctor is essential. As a rule, the disease cannot be completely cured, so that the disease always leads to the premature death of those affected. Parents and relatives in particular should therefore also seek psychological treatment for this disease.

A doctor should be consulted if the person affected shows very severe malformations or malformations all over the body. This also leads to significant difficulties in the everyday life of the patient, so that they are always dependent on the help and care of relatives. As a rule, there are also mental problems, since there are also malformations in the brain. The disease can be diagnosed immediately after birth or by a pediatrician. The further treatment then depends on the exact symptoms and is carried out by a specialist.

Treatment & Therapy

The disease cannot be cured. Children usually die in the womb or a week after birth at the latest. There are very few long-term survivors. The oldest patient with thanatophoric dysplasia was ten years old. The lungs of the small patients cannot develop and unfold properly due to the too narrow and narrow chest, so that the children develop respiratory insufficiency.

The ventilation of the lungs is severely restricted. The children suffer from shortness of breath and usually die from respiratory failure. This failure is compounded by damage to the respiratory center. Due to the too small diameter of the occipital foramen, the brainstem is compressed with the respiratory center.

This process cannot be stopped, so that at most a symptomatic therapy is carried out. The parents remain in the hospital with their newborn and receive pastoral support. Pain-relieving and sedative medication may be given to the child.


Thanatophoric dysplasia is an inherited disease. There is currently no effective prevention of the disease.


Thanatophore dysplasia (TD) is an incurable disease. It’s genetic. The extent of the follow-up measures is determined by the course of the disease. As a rule, the affected children die within their first few hours or days of life from respiratory failure or compression of the spinal cord or brainstem.

In the event of the death of the affected child, aftercare focuses on coping with the bereavement of the first-degree relatives. Psychotherapy with a focus on “grief” is generally recommended by doctors to cope with grief. In a very small number of all cases of illness, the sick children can still experience childhood.

However, this requires significant medical intervention. In this case, the aftercare measures focus on the careful care of the affected child, depending on the parents’ wishes. As a follow-up treatment, support of the child’s breathing with ventilation and tracheostomy is continued. Excessive accumulation of fluid in the child’s skull can be avoided by inserting a shunt during follow-up care.

Depending on the course of the disease, depending on the current clinical picture, clinical stays may be necessary to improve or stabilize the child’s health. Psychotherapy with a focus on “preparing for death” is recommended for parents. In order to make the remaining time as positive as possible, a children’s hospice, for example, should be asked for assistance.

You can do that yourself

Individuals with thanatophore dysplasia suffer from a fatal condition associated with numerous ailments. For this reason there are no effective self-help measures, since even with the best possible medical therapy there is no prospect of curing the disease.

Since it is a congenital disease and the patients usually die shortly after birth or as a newborn, but at the latest in infancy, self-help measures are generally not their responsibility. Only the legal guardians are able to alleviate the symptoms of the sick child by taking suitable measures. The patient usually remains in the hospital after the birth. Parents can provide emotional support to the newborn through regular visits and try to reduce the child’s stress. However, it is usually not possible for the parents to stay in the clinic for a long period of time. Patients with thanatophoric dysplasia usually require mechanical ventilation.

If those affected survive the newborn age and are allowed to leave the hospital temporarily or even live at home with their parents, frequent medical check-ups are still necessary. Ultimately, a children’s hospice is a way to make death easier for the patient himself and his family.

Thanatophoric Dysplasia