Asphyxiating thoracic dysplasia: Difference between revisions

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'''Asphyxiating thoracic dysplasia''' ('''ATD'''), also known as '''Jeune syndrome''', is a rare inherited bone growth disorder that primarily affects the thoracic region. It was first described in 1955 by the French pediatrician Mathis Jeune.<ref>{{Cite journal|last=de Vries|first=J.|last2=Yntema|first2=J. L.|last3=van Die|first3=C. E.|last4=Crama|first4=N.|last5=Cornelissen|first5=E. A. M.|last6=Hamel|first6=B. C. J.|date=January 2010|title=Jeune syndrome: description of 13 cases and a proposal for follow-up protocol|journal=European Journal of Pediatrics|volume=169|issue=1|pages=77–88|doi=10.1007/s00431-009-0991-3|issn=0340-6199|pmc=2776156|pmid=19430947}}</ref> 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]]). The restricted growth and expansion of the lungs caused by this disorder results in life-threatening breathing difficulties.
[[File:JeunessyndromeL.png|thumb|213x213px|left|Lateral CXR of the same person above]]
'''Asphyxiating Thoracic Dysplasia (ATD)''', also known as '''Jeune Syndrome''', is a rare genetic disorder characterized by skeletal abnormalities that primarily affect the thoracic region. This condition leads to a narrow, bell-shaped chest, which can restrict lung development and function, often resulting in severe respiratory distress. First described by the French pediatrician Mathis Jeune in 1955, ATD encompasses a spectrum of clinical manifestations, including:


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]]'', ''[[DYNC2H1]]'', ''[[WDR12|WDR19]]'', ''[[IFT140]]'' 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.<ref>{{Cite web|url=https://rarediseases.info.nih.gov/diseases/3049/jeune-syndrome|title=Jeune syndrome {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|access-date=2019-11-14}}</ref>
* '''[[Narrow thorax]]'''
* '''[[Short ribs]]'''
* '''[[Shortened limbs]]'''
* '''[[Polydactyly]]''' (extra fingers and/or toes)
* '''[[Renal anomalies]]'''
* '''[[Hepatic fibrosis]]'''
* '''[[Retinal dystrophy]]'''


==Types==
The incidence of ATD is estimated to be between 1 in 100,000 to 130,000 live births. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to manifest the disease.


{| class="wikitable"
== Clinical Features ==
|-
! Type
! [[OMIM]]
! Gene
! Locus
|-
| ATD1
| {{OMIM|208500||none}}
| ?
| 15q13
|-
| ATD2
| {{OMIM|611263||none}}
| [[IFT80]]
| 3q
|-
| ATD3
| {{OMIM|613091||none}}
| [[DYNC2H1]]
| 11q
|}


==Signs and symptoms==
The clinical presentation of ATD is highly variable, ranging from mild forms with minimal respiratory involvement to severe cases leading to perinatal death. Key clinical features include:
[[File:JeunessyndromeL.png|thumb|213x213px|left|Lateral CXR of the same person above]]
 
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]], [[pelvis]], arms and legs.<ref>{{Cite web|url=https://ghr.nlm.nih.gov/condition/asphyxiating-thoracic-dystrophy|title=Asphyxiating thoracic dystrophy|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2019-11-14}}</ref> 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]]s, and over time they may experience [[kidney failure]]. As a result, few children with Jeune syndrome live into their teen years. Children with Jeune syndrome have a form of [[dwarfism]]. They are short in stature, and their arms and legs are shorter than most people’s.<ref>{{Cite journal|last=Jeune|first=M.|last2=Beraud|first2=C.|last3=Carron|first3=R.|date=1955|title=[Asphyxiating thoracic dystrophy with familial characteristics]|journal=Archives Françaises de Pédiatrie|volume=12|issue=8|pages=886–891|issn=0003-9764|pmid=13292988}}</ref>
=== Respiratory System ===
 
* '''Narrow, bell-shaped chest''': The hallmark of ATD is a constricted thoracic cavity due to short ribs, leading to respiratory insufficiency. Newborns may present with rapid, shallow breathing and may require respiratory support.
 
* '''Pulmonary hypoplasia''': Underdevelopment of the lungs is common, contributing to breathing difficulties and increased susceptibility to respiratory infections.
 
=== Skeletal System ===
 
* '''Shortened limbs''': Both upper and lower limbs may be shorter than average, often accompanied by metaphyseal abnormalities.
* '''Polydactyly''': Extra digits on hands and/or feet are frequently observed.
* '''Pelvic anomalies''': Irregularities in pelvic bone development can occur, potentially affecting mobility.
 
=== Renal and Hepatic Involvement ===
 
* '''Renal disease''': Cystic kidney disease may develop, leading to impaired kidney function or chronic kidney disease.
* '''Hepatic fibrosis''': Liver involvement can result in fibrosis, potentially progressing to liver dysfunction.
 
=== Ocular Manifestations ===
 
* '''Retinal dystrophy''': Progressive retinal degeneration can lead to vision impairment or blindness.
 
== Genetic Basis ==
 
ATD is classified as a ciliopathy, a disorder arising from defects in the structure or function of cilia—microscopic, hair-like structures on the surface of cells. Mutations in several genes encoding proteins involved in ciliary function have been implicated in ATD, including:
 
* '''[[IFT80]]'''
* '''[[DYNC2H1]]'''
* '''[[WDR19]]'''
* '''[[IFT140]]'''
* '''[[TTC21B]]'''
 
These genetic mutations disrupt normal ciliary function, leading to the diverse clinical manifestations observed in ATD.
 
== Diagnosis ==
 
Diagnosis of ATD involves a combination of clinical evaluation, imaging studies, and genetic testing:
 
* '''Clinical Evaluation''': Assessment of physical characteristics such as chest shape, limb length, and presence of polydactyly.
 
* '''Imaging Studies''':
** '''[[Radiography]]''': X-rays reveal short ribs, narrow thoracic cavity, and pelvic anomalies.
** '''[[Ultrasonography]]''': Prenatal ultrasound can detect characteristic skeletal abnormalities.
 
* '''Genetic Testing''': Identification of mutations in genes associated with ciliary function confirms the diagnosis.
 
== Management and Prognosis ==
 
Management of ATD is multidisciplinary, focusing on addressing respiratory, renal, and orthopedic complications:
 
=== Respiratory Support ===
 
* '''Mechanical ventilation''': Necessary for newborns with severe respiratory distress.
 
* '''Surgical interventions''': Procedures such as the implantation of vertical expandable prosthetic titanium ribs (VEPTR) can expand the thoracic cavity, improving lung capacity and function.
 
=== Renal Management ===
 
* '''Monitoring''': Regular assessment of kidney function is essential.
 
* '''Interventions''': Management of renal impairment may include medication, dialysis, or kidney transplantation in severe cases.
 
=== Orthopedic Care ===
 
* '''Physical therapy''': Aims to improve mobility and strength.
 
* '''Surgical correction''': Addressing limb deformities or polydactyly to enhance function and appearance.
 
=== Prognosis ===


==Diagnosis==
The prognosis of ATD varies based on the severity of thoracic constriction and associated complications. Severe cases with significant respiratory involvement have a high mortality rate in infancy. However, individuals with milder forms may survive into adulthood, though they remain at risk for renal and hepatic complications.
Jeune syndrome is a rare autosomal recessive [[ciliopathy]].<ref name=":0" /> This diagnosis is grouped with other chest problems called [[thoracic insufficiency syndrome]] (TIS). Diagnosis of Jeune syndrome can be made as early as before birth if signs and symptoms are apparent on an [[ultrasound]]; however, diagnosis after birth usually occurs through X-rays and genetic testing, such as the tests found on the [https://www.ncbi.nlm.nih.gov/gtr/ Genetic Testing Registry] (GTR).<ref>{{Cite book|url=https://books.google.com/books?id=53Csy-mr1bsC&pg=PA673|title=Fetology: Diagnosis & Management of the Fetal Patient|last=Bianchi|first=Diana W.|last2=Crombleholme|first2=Timothy M.|last3=D'Alton|first3=Mary E.|date=2000|publisher=McGraw Hill Professional|isbn=9780838525708}}</ref>


==Treatment==
== Research and Future Directions ==


=== Medical care ===
Ongoing research aims to better understand the genetic and molecular mechanisms underlying ATD, with the goal of developing targeted therapies. Advances in prenatal imaging and genetic testing facilitate early diagnosis, allowing for timely interventions that may improve outcomes. Additionally, innovations in surgical techniques and respiratory support continue to enhance the quality of life for individuals with ATD.
In order to help relieve respiratory distress, [[mechanical ventilation]] 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]].


=== Surgical care ===
== See Also ==
In severe cases, surgical action is needed; otherwise, failure to intervene can result in pulmonary damage and eventual fatality. [[Vertical Expandable Prosthetic Titanium Rib|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.<ref>{{Cite web|url=https://www.chop.edu/conditions-diseases/jeune-syndrome|title=Jeune Syndrome|last=Philadelphia|first=The Children's Hospital of|date=2018-07-31|website=www.chop.edu|access-date=2019-11-14}}</ref> Alternatively, lateral thoracic expansion is used to enlarge the chest wall by separating the ribs from their [[periosteum]] 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 [[Median sternotomy|sternotomy]] and fixation with bone grafts, or a [[Methyl methacrylate|methylmethacrylate]] prostheses plate.<ref name=":0">{{Cite journal|date=2019-11-10|title=Asphyxiating Thoracic Dystrophy (Jeune Syndrome) Treatment & Management: Approach Considerations, Medical Care, Surgical Care|url=https://emedicine.medscape.com/article/945537-treatment#showall}}</ref>


== References ==
* '''[[Ciliopathy]]'''
{{reflist}}
* '''[[Skeletal dysplasia]]'''
* '''[[Polydactyly]]'''
* '''[[Pulmonary hypoplasia]]'''


== External links ==
== External links ==
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{{Ciliopathy}}
{{Ciliopathy}}
{{Cytoskeletal defects}}
{{Cytoskeletal defects}}
 
{{stub}}
[[Category:Ciliopathy]]
[[Category:Ciliopathy]]
[[Category:Cytoskeletal defects]]
[[Category:Cytoskeletal defects]]
{{dictionary-stub1}}

Latest revision as of 13:02, 19 March 2025

Asphyxiating thoracic dysplasia
Synonyms Jeune syndrome, asphyxiating thoracic chondrodystrophy, infantile thoracic dystrophy
Pronounce
Field
Symptoms Narrow chest, short ribs, shortened bones of the arms and legs, unusually shaped pelvis, and extra fingers and/or toes
Complications
Onset
Duration
Types
Causes
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment Mechanical ventilation, endotracheal suctioning, postural drainage, Vertical expandable prosthetic titanium rib (VEPTR), Lateral thoracic expansion, or other chest reconstruction surgeries.
Medication
Prognosis
Frequency 1 in 100,000 to 130,000
Deaths Mortality of affected: 60-70%


Lateral CXR of the same person above

Asphyxiating Thoracic Dysplasia (ATD), also known as Jeune Syndrome, is a rare genetic disorder characterized by skeletal abnormalities that primarily affect the thoracic region. This condition leads to a narrow, bell-shaped chest, which can restrict lung development and function, often resulting in severe respiratory distress. First described by the French pediatrician Mathis Jeune in 1955, ATD encompasses a spectrum of clinical manifestations, including:

The incidence of ATD is estimated to be between 1 in 100,000 to 130,000 live births. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to manifest the disease.

Clinical Features[edit]

The clinical presentation of ATD is highly variable, ranging from mild forms with minimal respiratory involvement to severe cases leading to perinatal death. Key clinical features include:

Respiratory System[edit]

  • Narrow, bell-shaped chest: The hallmark of ATD is a constricted thoracic cavity due to short ribs, leading to respiratory insufficiency. Newborns may present with rapid, shallow breathing and may require respiratory support.
  • Pulmonary hypoplasia: Underdevelopment of the lungs is common, contributing to breathing difficulties and increased susceptibility to respiratory infections.

Skeletal System[edit]

  • Shortened limbs: Both upper and lower limbs may be shorter than average, often accompanied by metaphyseal abnormalities.
  • Polydactyly: Extra digits on hands and/or feet are frequently observed.
  • Pelvic anomalies: Irregularities in pelvic bone development can occur, potentially affecting mobility.

Renal and Hepatic Involvement[edit]

  • Renal disease: Cystic kidney disease may develop, leading to impaired kidney function or chronic kidney disease.
  • Hepatic fibrosis: Liver involvement can result in fibrosis, potentially progressing to liver dysfunction.

Ocular Manifestations[edit]

  • Retinal dystrophy: Progressive retinal degeneration can lead to vision impairment or blindness.

Genetic Basis[edit]

ATD is classified as a ciliopathy, a disorder arising from defects in the structure or function of cilia—microscopic, hair-like structures on the surface of cells. Mutations in several genes encoding proteins involved in ciliary function have been implicated in ATD, including:

These genetic mutations disrupt normal ciliary function, leading to the diverse clinical manifestations observed in ATD.

Diagnosis[edit]

Diagnosis of ATD involves a combination of clinical evaluation, imaging studies, and genetic testing:

  • Clinical Evaluation: Assessment of physical characteristics such as chest shape, limb length, and presence of polydactyly.
  • Imaging Studies:
    • Radiography: X-rays reveal short ribs, narrow thoracic cavity, and pelvic anomalies.
    • Ultrasonography: Prenatal ultrasound can detect characteristic skeletal abnormalities.
  • Genetic Testing: Identification of mutations in genes associated with ciliary function confirms the diagnosis.

Management and Prognosis[edit]

Management of ATD is multidisciplinary, focusing on addressing respiratory, renal, and orthopedic complications:

Respiratory Support[edit]

  • Mechanical ventilation: Necessary for newborns with severe respiratory distress.
  • Surgical interventions: Procedures such as the implantation of vertical expandable prosthetic titanium ribs (VEPTR) can expand the thoracic cavity, improving lung capacity and function.

Renal Management[edit]

  • Monitoring: Regular assessment of kidney function is essential.
  • Interventions: Management of renal impairment may include medication, dialysis, or kidney transplantation in severe cases.

Orthopedic Care[edit]

  • Physical therapy: Aims to improve mobility and strength.
  • Surgical correction: Addressing limb deformities or polydactyly to enhance function and appearance.

Prognosis[edit]

The prognosis of ATD varies based on the severity of thoracic constriction and associated complications. Severe cases with significant respiratory involvement have a high mortality rate in infancy. However, individuals with milder forms may survive into adulthood, though they remain at risk for renal and hepatic complications.

Research and Future Directions[edit]

Ongoing research aims to better understand the genetic and molecular mechanisms underlying ATD, with the goal of developing targeted therapies. Advances in prenatal imaging and genetic testing facilitate early diagnosis, allowing for timely interventions that may improve outcomes. Additionally, innovations in surgical techniques and respiratory support continue to enhance the quality of life for individuals with ATD.

See Also[edit]

External links[edit]

Diseases of cilia
Structural
Signaling
Other/ungrouped



Cytoskeletal defects
Microfilaments
IF
1/2
3
4
5
Microtubules
Membrane
Catenin


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