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Pediatrics: Genetics and Metabolic Disease > Genetics
Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Article Last Updated: Jul 23, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Harold Chen, MD, MS, FAAP, FACMG, Professor, Departments of Pediatrics, Obstetrics and Gynecology, Pathology, Director of Perinatal Genetics and Genetic Laboratory Services, Louisiana State University Medical Center; Laboratory Director, Hema-Con Cancer Cytogenetics Laboratory, Gainesville, Florida
Harold Chen is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Human Genetics, and Teratology Society
Editors: James Bowman, MD, Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Hagop Youssoufian, MD, MSc, Vice President of Clinical Research, ImClone Systems Incorporated; Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System; Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
asphyxiating thoracic dysplasia, infantile thoracic dystrophy, thoracic-pelvic-phalangeal dystrophy, severely narrow thorax, congenital dwarfism, skeletal dysplasia, lung hypoplasia, renal lesions, renal failure, Jeune syndrome, asphyxiating thoracic dystrophy, bilateral microcystic renal disease, tubular atrophy, alveolar hypoventilation
Background
In 1955, Jeune et al described familial asphyxiating thoracic dystrophy in a pair of siblings with severely narrow thoraxes. This condition is also known as Jeune syndrome. Jeune syndrome, a potentially lethal congenital dwarfism, is a rare autosomal recessive disorder characterized by typical skeletal dysplasias, such as a narrow thorax and micromelia, with respiratory and renal manifestations. Respiratory symptoms widely vary from respiratory failure and infantile death to latent phenotype without respiratory symptoms.
Pathophysiology
Classic manifestations in infancy include dwarfism with short ribs, short limbs, and characteristic radiographic changes in the ribs and pelvis. The severity of clinical and radiographic features varies. All patients have small chests, but the degree of the respiratory distress varies from negligible to rapidly fatal. Lung hypoplasia, presumably due to a restricted thoracic cage, is the major cause of death in infancy. Renal lesions lead to progressive renal failure later in life. Variability in clinical, radiographic, and pathological manifestations may be related to genetic heterogeneity.
Frequency
United States
Incidence is estimated at 1 per 100,000-130,000 live births.
Mortality/Morbidity
- Although Jeune syndrome may be associated with bilateral microcystic renal disease, which may gradually progress to tubular atrophy and renal failure, the most common and prominent clinical presentation is alveolar hypoventilation. Alveolar hypoventilation is caused by impaired chest expansion as a result of short horizontally placed ribs.
- Furthermore, most patients with Jeune syndrome (approximately 60-70%) die from respiratory failure in early infancy and early childhood. Chronic renal failure may ensue in survivors.
- Few patients reach adolescence or adulthood.
Race
Jeune syndrome has no race predilection.
Sex
The syndrome is not associated with any sex predilection.
Age
Jeune syndrome may be detected at birth or during infancy because of typical clinical and radiographic signs.
History
Clinical presentations of lethal, severe, and latent forms of Jeune syndrome vary.
- Respiratory distress
- Respiratory distress may occur secondary to a small thorax. The thorax remains motionless, and respiration is entirely abdominal. Considerable supraclavicular and suprasternal retraction of the intercostal space may be present upon inspiration.
- Severe dyspnea and extreme cyanosis may occur. However, some infants have only respiratory symptoms in conjunction with infection.
- Some individuals with Jeune syndrome have no respiratory symptoms in infancy or childhood.
- Chest deformity of varying degree
- Short-limbed dwarfism
- Other symptoms: History may also reveal failure to thrive, gastroenteritis, recurrent rectal prolapse, diarrhea, congestive cardiac failure, puffy face, and ankle swelling.
Physical
- Dwarfism is noted.
- Thoracic findings are as follows:
- A long, narrow, and abnormally small thorax with reduced thoracic cage capacity; lung hypoplasia; and respiratory distress usually lead to early death.
- The small thorax usually improves with age for those who survive early childhood.
- Limbs exhibit variable micromelia and short digits with bulbous terminal phalanges and occasional postaxial polydactyly of the hands and feet.
- Eyes exhibit occasional retinal degeneration.
- Patients may have occasional intestinal malabsorption.
- Renal failure may develop during infancy, early adolescence, or second decade of life.
- Polyuria, polydipsia, and hypertension may be present during the second or third year of life.
- Occasional involvement of the liver may include prolonged neonatal jaundice, polycystic liver disease, hyperplasia of the bile ducts, and congenital hepatic cirrhosis.
- Occasional involvement of the heart may include cardiac failure secondary to increased pulmonary vascular resistance, thoracic constriction, alveolar hypoplasia, and possible intrinsic myocardial disease.
- Cystic changes of pancreatic ducts and pancreatic exocrine insufficiency may be present in long-term survivors of Jeune syndrome.
- Occasional involvement of the teeth, nails, and other organs may occur.
Causes
- Jeune syndrome is known to be genetically heterogeneous. One locus is at chromosome 15q13. Another locus is at chromosome 3q24-3q26.
- Jeune syndrome is the first chondrodysplasia to be linked to a defect in intraflagellar transport (IFT) or primary cilia function.
- Recessive mutation in IFT80, which encodes a conserved intraflagellar transport protein, has been shown in Jeune syndrome.
Achondrogenesis
Achondroplasia
Cartilage-Hair Hypoplasia
Ellis-van Creveld Syndrome
Hypophosphatasia
Thanatophoric Dysplasia
Other Problems to be Considered
Diastrophic dysplasia Barnes syndrome (thoracolaryngopelvic dysplasia) (OMIM 187760): This is an autosomal dominant disorder characterized by a small bell-shaped thorax, laryngeal stenosis, and small iliac wing and pelvis. Short rib polydactyly syndrome type I (Saldino-Noonan syndrome) (OMIM 263530): This is a lethal condition of newborns characterized by hydropic appearance, postaxial polydactyly, severely shortened and flipperlike limbs, and striking metaphyseal dysplasia of tubular bones. The pelvis resembles that of Ellis-van Creveld syndrome and Jeune syndrome, with small ilia and osseous spurs projecting medially and laterally from the acetabular roofs. As in type II, polycystic kidneys, transposition of great vessels, and atretic lesions of the gastrointestinal and genitourinary systems occur. Short rib polydactyly syndrome type II (Majewski syndrome) (OMIM 263520): This is a lethal entity characterized by median cleft lip, preaxial and postaxial polysyndactyly, short ribs and limbs, genital abnormalities, and anomalies of epiglottis and viscera. Short rib polydactyly syndrome type III (Verma-Naumoff syndrome) (OMIM 26351): This is a lethal entity characterized by a short cranial base, bulging forehead, depressed nasal bridge, and flat occiput. Another difference is the radiologic appearance of the long tubular bones, which have a distinct corticomedullary demarcation, somewhat widened metaphyses, and marked longitudinal spurs. Short rib syndrome (Beemer-Langer syndrome) (OMIM 269860): This is a lethal entity characterized by hydrops, ascites, median cleft of the upper lip, narrow chest, and short bowed limbs.
Lab Studies
- Urinalysis
- Hematuria
- Proteinuria
- Defective urine concentrating capacity
- Arterial blood gas (ABG): Hypoxia and hypercarbia in room air reflect severe restrictive lung disease.
Imaging Studies
- Newborn and infant radiography
- Small and bell-shaped thorax with reduced transverse and anterior-posterior diameter
- Short and horizontally oriented ribs with irregular costochondral junctions and bulbous and irregular anterior ends
- Short squared iliac wings
- Trident appearance of acetabular margin
- Short limbs relative to trunk
- Variable limb-shortening
- Short phalanges, metacarpals, or metatarsals with or without polydactyly
- Premature ossification of the capital femoral epiphyses
- Childhood radiology
- Relatively large thorax with growth of ribs
- Short ilium with normal flaring of iliac wings
- Striking cone-shaped epiphyses and early fusion between the epiphyses and metaphyses of the distal and middle phalanges
- Short distal and middle phalanges
- Varying shortening of extremities relative to trunk
- Prenatal ultrasonography
- Detection of affected second- and third-trimester fetuses of at-risk families has been reported.
- Characteristic findings include a narrow thorax, short hypoplastic ribs, and short tubular bones.
- Other ultrasonographic findings include polyhydramnios and absent or feeble fetal respiratory movements.
Other Tests
- Pulmonary function testing may reveal severe restrictive lung disease.
Procedures
- Renal biopsy may reveal cystic tubular dysplasia with or without glomerular sclerosis.
Histologic Findings
- Lungs - Hypoplastic lungs due to a marked reduction in the number of alveolar ducts and alveoli (hypoplasia of alveoli)
- Cartilages - Irregular endochondral ossification with patchy distribution of physeal zone of hypertrophy and radiologically irregular metaphyseal ends (asphyxiating thoracic dystrophy type I) and diffusely retarded and disorganized physes with smooth cartilage bone junctions and radiologically smooth metaphyseal ends (asphyxiating thoracic dystrophy type II)
- Kidneys - Cystic renal dysplasia and hypoplasia, nephronophthisis or interstitial nephritis (diffuse interstitial and periglomerular fibrosis, round cell lymphocytic infiltration, hyalinized glomeruli, pericapsular thickening, thickened basement membrane, dilated or atrophic tubules), pyelonephritis with scarring, and distortion of renal parenchyma
- Liver - Periportal hepatic fibrosis, bile duct proliferation, and early cirrhosis
Medical Care
- Medical care is supportive.
- Mechanical ventilation is urgently required in the most severe cases, in which respiratory distress develops immediately after birth. Less-severe cases gradually progress to respiratory failure as a result of multiple recurrent pulmonary infections.
- Treat respiratory infections vigorously with antibiotics, endotracheal suctioning, and postural drainage.
- Nasogastric or gastrostomy feedings may be required.
- Genetic counseling is indicated. The parents of a child affected with Jeune syndrome are obligatory carriers with a 25% recurrence risk.
Surgical Care
- Surgery is indicated only in the most severe cases in which failure to intervene will result in progressive pulmonary damage and eventual death. No data is currently available on long-term follow-up care of patients who have been surgically treated.
- Chest reconstruction and enlargement of the thoracic cage by sternotomy and fixation with bone grafts or a methylmethacrylate prosthesis plate provides patients with the time needed for thoracic cage growth. Bone grafting can completely fill midsternal defect, thus preventing lung herniation, and supplies equal support along the sternal wound edges, avoiding localized high-pressure areas. No ribs or iliac crest grafts have to be harvested from the patient. A methylmethacrylate prosthesis can be made before surgery, thus saving considerable anesthesia time. The prosthesis supplies support along the entire length of the sternal edges to prevent herniation of the heart and lungs. The material is inert and the prosthesis can be replaced later if a larger strut is needed.
- A second-stage procedure is needed to provide a better and more natural environment for further continuous expansion of the chest.
- A procedure of lateral thoracic expansion was recently described in Jeune syndrome. The chest wall is enlarged by dividing the ribs and underlying tissue in a staggered fashion so that either rib or periosteum covers the lung. New bone formation has been demonstrated, and viable enlargement has been obtained. This procedure has been found to be safe and effective in selected patients older than one year.
- A vertical expandable prosthetic titanium rib is a new and safe tool used to treat children with thoracic insufficiency syndrome. It may decrease carbon dioxide retention in some patients and may be most beneficial in younger children.
- Dialysis and renal transplantation are indicated for renal failure. Recently, cadaver renal transplantation was successful in a 10-year-old boy with Jeune syndrome type 2.
Consultations
- Clinical geneticist
- Radiologist
- Anesthesiologist
- Pediatric surgeon
Diet
No special diet is required.
Activity
No restriction of activities is required for survivors of this condition.
Drug therapy is currently not a component of the standard of care for this condition.
Further Inpatient Care
- Treat postoperative ventilatory problems, and minimize secondary damage to lungs caused by prolonged ventilatory support.
- Treat respiratory infections and cardiac insufficiency.
Complications
- Pneumothorax
- Mucous plugging of a bronchus
- Repeated infections
- Progressive herniation of lung through sternal defect
- Cardiac insufficiency
- Development of significant respiratory compromise after pectus excavatum repair
- Respiratory compromise generally develops years after the original pectus operation.
- Most patients exhibit severe growth retardation of the upper chest wall resulting in restrictive pulmonary function test results.
Prognosis
- Prognosis is difficult to predict in each individual case because frequent pulmonary complications and cystic renal lesions are not always directly related to severity of skeletal changes.
- Jeune syndrome is compatible with life, although respiratory failure and infections are often fatal during infancy.
- The severity of thoracic constriction widely varies. For those patients who survive infancy, the thorax tends to revert to normal with improving respiratory function. This suggests that the lungs have a normal growth potential and the respiratory problems are secondary to restricted rib cage deformity.
- Renal failure may ensue later. Renal involvement is the major prognostic factor in those patients who survive the respiratory insufficiency during infancy.
- Survivors are short in stature.
Patient Education
- Up-to-date information about the syndrome and resources should be available to the families. The following organizations can provide useful information:
- Jeune's Syndrome Support Network
c/o Kurt Hernon
1400 S Lakeview Boulevard
Lorain, OH 44052
Phone: 440-246-1578
email: kurage@centuryinter.net - Jeune Family Support Group
Asphyxiating Thoracic Dystrophy
3710 W Temperance
Lambertville, MI 48144
Phone: 313-854-8132 - Little People of America (LPA), Inc.
PO Box 745
Lubbock, TX 79408
Phone: 888-LPA-2001
email: LPADataBase@juno.com - International Skeletal Dysplasia Registry
Cedars-Sinai Medical Center
444 S San Vicente Boulevard, Suite 1001
Los Angeles, CA 90048
Phone: 310-855-7488
e-mail: mpriore@mailgate.csmc.edu - International Center for Skeletal Dysplasia
St Joseph Hospital
7620 York Road
Towson, MD 21204
Phone: 410-337-1250
Medical/Legal Pitfalls
- Failure to give genetic counseling after confirmation of the diagnosis
- Recurrence risk is 25%.
- Prenatal diagnosis by ultrasonography is possible in the second trimester.
| Media file 1:
An infant with Jeune syndrome. Note the narrow chest and shortened upper extremities. |
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| Media file 2:
A child with Jeune syndrome. Note long narrow thorax with respiratory difficulty. |
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| Media file 3:
Note cystic renal dysplasia on the left kidney and renal hypoplasia on the right kidney. |
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| Media file 5:
Note the shortened upper extremity with acromelic shortening. |
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Asphyxiating Thoracic Dystrophy (Jeune Syndrome) excerpt Article Last Updated: Jul 23, 2007
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