Asphyxiating thoracic dysplasia (ATD), also known as Jeune syndrome, is a rare inherited bone growth disorder (autosomal recessive skeletal dysplasia) that primarily affects the thoracic region. It was first described in 1955 by the French pediatrician Mathis Jeune. Common signs and symptoms can include a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (

polydactyly Polydactyly or polydactylism (), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes). Signs and symptoms In humans ...

). The restricted growth and expansion of the lungs caused by this disorder results in life-threatening breathing difficulties; occurring in 1 in every 100,000-130,000 live births in the United States. People who are affected with this disorder live short lives either only into infancy or early childhood. If they live beyond childhood, breathing problems can improve with age, but there is a possibility of developing severe kidney or heart problems. Several mutations in different genes such as ''

IFT80 Intraflagellar transport protein 80 homolog (IFT80), also known as WD repeat-containing protein 56, is a protein that in humans is encoded by the ''IFT80'' gene. Function IFT80 is part of the intraflagellar transport complex B and is necessary ...

'', ''

DYNC2H1 Cytoplasmic dynein 2 heavy chain 1 is a protein that in humans is encoded by the ''DYNC2H1'' gene. It is associated with Short rib-polydactyly syndrome type 3. It is also associated with Asphyxiating thoracic dysplasia. See also * dynein Dy ...

'', '' WDR19'', ''

IFT140 IFT140, Intraflagellar transport 140 homolog, is a protein that in humans is encoded by the ''IFT140'' gene. The gene product forms a core component of IFT-A complex which is indipensible for retrograde intraflagellar transport within the primary ...

'' and '' TTC21B'' have been identified in some families with the condition as possible causes of the disorder. Treatment is based on the signs and symptoms present in each person.

Types

Signs and symptoms

Jeune syndrome is a rare genetic disorder that affects the way a child’s cartilage and bones develop. It begins before the child is born and primarily affects the child's

rib cage The rib cage, as an enclosure that comprises the ribs, vertebral column and sternum in the thorax of most vertebrates, protects vital organs such as the heart, lungs and great vessels. The sternum, together known as the thoracic cage, is a semi- ...

pelvis The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also called bony pelvis, or pelvic skeleton). The ...

, arms and legs. Usually, problems with the rib cage cause the most serious health problems for children with Jeune syndrome. Their rib cages (thorax) are smaller and narrower than usual, which inhibits the child's lungs from developing fully or expanding when they inhale. The child may breathe rapidly and shallowly. They may have trouble breathing when they have an upper or lower respiratory infection, like pneumonia. Breathing trouble can range from mild to severe. In some children, it is not noticeable, aside from fast breathing; however, in others, breathing problems can be fatal. About 60% to 70% of children with this condition die from respiratory failure as babies or young children. Children with Jeune syndrome who survive often develop problems with their

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s, and over time they may experience

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. As a result, few children with Jeune syndrome live into their teen years. Children with Jeune syndrome have a form of

dwarfism Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...

. They are short in stature, and their arms and legs are shorter than most people’s.

Diagnosis

Jeune syndrome is a rare autosomal recessive

ciliopathy A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...

. This diagnosis is grouped with other chest problems called

thoracic insufficiency syndrome Thoracic insufficiency syndrome is the inability of the thorax to support normal respiration. It is frequently associated with chest and/or spinal abnormalities. Treatment options are limited, but include supportive pulmonary care and surgical o ...

(TIS). Diagnosis of Jeune syndrome can be made as early as before birth if signs and symptoms are apparent on an

ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...

; however, diagnosis after birth usually occurs through X-rays and genetic testing, such as the tests found on th
Genetic Testing Registry
(GTR).

Treatment

Medical care

In order to help relieve respiratory distress,

mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...

is required in most severe cases; while pulmonary infections that tend to lead to respiratory failure occur in less severe cases. In order to treat these infections, doctors may suggest antibiotics, endotracheal suctioning, or

postural drainage Postural drainage (PD) is the drainage of lung secretions using gravity. It is used to treat a variety of conditions that cause the build-up of secretions in the lungs. Uses Postural drainage is used to treat any condition that causes the build- ...

Surgical care

In severe cases, surgical action is needed; otherwise, failure to intervene can result in pulmonary damage and eventual fatality. Vertical expandable prosthetic titanium rib (VEPTR) surgery is the most common treatment for severe chest wall deformities. During this procedure, one or more titanium rods are attached to the ribs near the spine, which allow space for the patient’s lungs to develop. Small adjustments are made every four to six months through a small incision in the patient's back. Alternatively, lateral thoracic expansion is used to enlarge the chest wall by separating the ribs from their

periosteum The periosteum is a membrane that covers the outer surface of all bones, except at the articular surfaces (i.e. the parts within a joint space) of long bones. Endosteum lines the inner surface of the medullary cavity of all long bones. Structure ...

and covering them with titanium struts. This procedure is common among patients older than a year due to its safe and effective outcome. Chest reconstruction is another surgical procedure that promotes thoracic cage growth. It can be done as an enlargement of the thoracic cage by sternotomy and fixation with bone grafts, or a methylmethacrylate prostheses plate.

References

External links

{{Cytoskeletal defects Ciliopathy Cytoskeletal defects