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Ciliopathy

Jeune asphyxiating thoracic dystrophy

This condition is characterised by a small, narrow chest and short limbs, often leading to breathing difficulties. It is a ciliopathy, meaning it involves defects in tiny cell structures called cilia, and affects individuals from birth.

Autosomal recessive Ciliopathy OMIM:208500
1:100,000-130,000
Prevalence
Population estimate
25%
Inheritance
Autosomal recessive - chance of passing to each child
3
Associated genes
DYNC2H1, IFT80, WDR19

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
DYNC2H1 - 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

Jeune asphyxiating thoracic dystrophy (JATD), also known as asphyxiating thoracic dystrophy, is a rare genetic condition that impacts bone growth and development. The most distinguishing feature is a small, constricted rib cage, which can severely restrict lung development and breathing [PMID:31720490]. In addition to skeletal abnormalities, JATD can also affect other parts of the body, including the kidneys, liver, and eyes.

JATD is classified as a ciliopathy, a group of disorders caused by problems with cilia. Cilia are small, hair-like structures found on the surface of most cells in the body, where they play vital roles in cell signalling and movement of substances. Dysfunction in cilia can lead to a wide range of health issues affecting multiple organ systems.

The severity of JATD can vary significantly, even within the same family. While some individuals may experience life-threatening respiratory complications early in life, others might have milder symptoms and a better prognosis. The estimated prevalence of JATD is between 1 in 100,000 and 1 in 130,000 births.

Symptoms & clinical features

The primary symptoms of Jeune asphyxiating thoracic dystrophy relate to skeletal abnormalities. Infants are typically born with a characteristically small and narrow chest, often described as a 'bell-shaped' thorax. This limited chest cavity restricts lung expansion, leading to severe breathing difficulties, which can be life-threatening shortly after birth [PMID:31720490]. Babies with JATD often present with rapid breathing (tachypnoea) and may require respiratory support.

Other common skeletal features include short limbs, particularly in the upper arms and thighs (rhizomelic shortening), and short fingers and toes (brachydactyly). There may also be extra fingers or toes (polydactyly), and hip joint abnormalities [PMID:31720490]. Over time, some individuals may develop kidney problems, which can range from mild dysfunction to severe kidney failure, or liver complications. Less commonly, vision problems and retinal degeneration have been reported.

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Affected organs

Jeune asphyxiating thoracic dystrophy primarily affects the skeletal system, with the rib cage being most prominently involved. The narrow, short rib cage restricts lung development and function, making the lungs a critically affected organ. This can lead to severe respiratory insufficiency.

Beyond the skeleton and lungs, JATD can impact other organ systems. The kidneys are frequently affected, with potential issues including kidney cysts, kidney stones, and progressive kidney disease that can lead to renal failure. The liver may also be involved, with some individuals developing liver fibrosis. In some cases, the eyes can be affected, potentially leading to visual impairment due to retinal degeneration.

Multiple body systems
Multiple body systems
Systemic involvement
Cellular impact
Cellular impact
Mechanism at cellular level

Risks & severity

The severity of Jeune asphyxiating thoracic dystrophy is highly variable. In its most severe form, significant respiratory problems due to the small chest can be life-threatening shortly after birth, often requiring intensive medical intervention. Improvements in medical care, including advanced respiratory support, have increased survival rates for some infants [PMID:31720490].

For individuals who survive the neonatal period, long-term complications typically include chronic respiratory issues, progressive kidney disease, and sometimes liver problems. The risk of kidney failure can increase with age. While the condition can be life-limiting, the spectrum of severity means that some individuals may experience milder symptoms and have a longer life expectancy, particularly with careful medical management.

Genetic causes

Jeune asphyxiating thoracic dystrophy is a genetic condition caused by pathogenic changes (sometimes called mutations) in specific genes. These genes provide instructions for making proteins that are essential components of cilia, which are tiny, hair-like structures on the surface of cells. When these genes are altered, the cilia cannot function correctly, leading to the diverse symptoms seen in JATD.

Several genes are known to be associated with JATD. These include DYNC2H1, IFT80, and WDR19. For example, DYNC2H1 provides instructions for a protein that is part of the dynein-2 complex, which is crucial for moving materials within cilia, a process known as intraflagellar transport [PMID:27027010]. Pathogenic variants in any of these genes can disrupt this transport system, leading to the development of JATD. Research suggests that different genetic changes may contribute to the variation in disease severity observed in individuals.

  • DYNC2H1
    dynein cytoplasmic 2 heavy chain 1
    The DYNC2H1 gene provides instructions for a key protein involved in cilia function and intraflagellar transport, essential for cell signalling and skeletal development.
  • IFT80
    intraflagellar transport 80
  • WDR19
    WD repeat domain 19

Inheritance pattern

Jeune asphyxiating thoracic dystrophy has an autosomal recessive inheritance pattern. This means that a person must inherit two altered copies of the same gene - one from each parent - to develop the condition. Individuals who inherit only one altered copy of the gene are known as carriers. Carriers typically do not show symptoms of JATD, but they can pass the altered gene copy on to their children.

If both parents are carriers of a gene associated with JATD, there is a 25% (1 in 4) chance with each pregnancy that their child will inherit two altered copies and develop the condition. There is a 50% (2 in 4) chance that their child will be a carrier like them, and a 25% (1 in 4) chance that their child will inherit two unaffected gene copies and will not be a carrier or have the condition.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Diagnosis & testing

The diagnosis of Jeune asphyxiating thoracic dystrophy is often suspected based on characteristic clinical features observed at birth or during childhood, such as a narrow chest, short limbs, and breathing difficulties. Imaging studies, such as X-rays, can confirm the skeletal abnormalities.

Confirmation of JATD typically involves genetic testing. This can identify pathogenic variants in the genes known to be associated with the condition, such as DYNC2H1, IFT80, and WDR19. Genetic testing in the UK is usually accessed through the NHS Genomic Medicine Service (GMS) after a referral from a specialist clinician. The specific genetic test for JATD falls under certain R-codes within the GMS testing directory, facilitating accurate diagnosis and family planning. A clinical geneticist or genetic counsellor can help arrange and interpret these tests.

Management & lifestyle

Management for individuals with Jeune asphyxiating thoracic dystrophy is focused on addressing symptoms and preventing complications, often involving a multidisciplinary team. For newborns with severe respiratory compromise, immediate interventions such as respiratory support (e.g., ventilation) may be necessary. Surgical procedures to expand the chest cavity, such as vertical expandable prosthetic titanium rib (VEPTR) surgery, may be considered in some cases to improve lung function, although their suitability varies [PMID:22097951].

Ongoing care typically involves regular monitoring of kidney and liver function, with specific treatments provided as needed. Nutritional support and physiotherapy can also be important components of care. Families in the UK can access support through their local NHS trusts and specialist centres. Genetic counselling is offered to families to discuss the inheritance pattern, recurrence risks, and family planning options. Management plans are individualised and overseen by specialist paediatric teams.

UK care pathway

In the UK, individuals suspected of having Jeune asphyxiating thoracic dystrophy are typically referred to a paediatric specialist. If a genetic condition is suspected, a referral to a clinical genetics service is the next step. These services, part of the NHS Genomic Medicine Service (GMS), can arrange for appropriate genetic testing using the GMS testing directory and associated R-codes. Genetic counsellors within these services provide essential information and support, helping families understand the condition, its inheritance, and implications for future family planning.

Frequently asked questions

What is a ciliopathy?

A ciliopathy is a genetic disorder caused by problems with cilia, which are tiny, hair-like structures on the surface of most cells. Cilia are crucial for many cellular processes, including signalling and fluid movement. When they don't work correctly, it can lead to a wide range of symptoms affecting various organs.

How does Jeune asphyxiating thoracic dystrophy affect breathing?

Individuals with Jeune asphyxiating thoracic dystrophy typically have a very small, narrow rib cage. This restricted chest cavity prevents the lungs from expanding properly, leading to severe breathing difficulties. This can result in respiratory distress and inadequate oxygen intake, especially in infants.

Can Jeune asphyxiating thoracic dystrophy be detected before birth?

In some cases, characteristic features of Jeune asphyxiating thoracic dystrophy, such as a small chest or short limbs, may be visible on prenatal ultrasound scans. If these findings are noted, further investigations, including genetic testing of foetal samples, can be considered to confirm the diagnosis.

What is the long-term outlook for someone with JATD?

The long-term outlook for Jeune asphyxiating thoracic dystrophy varies significantly. While severe cases can be life-threatening in infancy due to breathing problems, improved medical interventions mean that many individuals survive. Long-term care often involves managing chronic respiratory issues, kidney problems, and other complications, with ongoing support from specialist medical teams.

If I have one child with JATD, what are the chances of a future child being affected?

If you have one child with Jeune asphyxiating thoracic dystrophy, it means both parents are carriers of an altered gene associated with the condition. With each subsequent pregnancy, there is a 25% (1 in 4) chance that another child will be affected. Genetic counselling can provide detailed information and support for family planning.

References

  1. Lehman AM, Eydoux P, Doherty D. Co-occurrence of Joubert syndrome and Jeune asphyxiating thoracic dystrophy. American journal of medical genetics. Part A. 2010. PMID: 20503315
  2. Kikuchi N, Kashiwa H, Ogino T. The Nuss technique for Jeune asphyxiating thoracic dystrophy repair in siblings. Annals of plastic surgery. 2010. PMID: 20606585
  3. Tuz K, Bachmann-Gagescu R, O'Day DR. Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. American journal of human genetics. 2014. PMID: 24360808
  4. Schmidts M, Hou Y, Cortés CR. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport. Nature communications. 2015. PMID: 26044572
  5. Shaheen R, Schmidts M, Faqeih E. A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies. Human molecular genetics. 2015. PMID: 25361962
  6. Faudi E, Brischoux-Boucher E, Huber C. A new case of KIAA0753-related variant of Jeune asphyxiating thoracic dystrophy. European journal of medical genetics. 2020. PMID: 31816441
  7. Ho NC, Francomano CA, van Allen M. Jeune asphyxiating thoracic dystrophy and short-rib polydactyly type III (Verma-Naumoff) are variants of the same disorder. American journal of medical genetics. 2000. PMID: 10710229
  8. Asseri AA, Alzoani AA, Almahdi M. Whole-Exome Sequencing Identifies DYNC2H1 Mutations as a Cause of Jeune Asphyxiating Thoracic Dystrophy Without Extra-Skeletal Organ Involvement. International medical case reports journal. 2024. PMID: 38550721
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor.