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2001-02-18-10 Asphyxiating thoracic dystrophy © Sleurs www.thefetus.net/

Asphyxiating thoracic dystrophy

Elke Sleurs, MD*&, Werther Adrian Clavelli, MD

*Vrije Universiteit Brussel  and &Women’s Health Alliance, Nashville TN,

Diagnostico Maipu, Buenos Aires, Argentina 

Synonyms: Jeune syndrome (first described by Jeune et al.[1] in 1955), Jeune Thoracic Dystrophy, Thoracic-Pelvic-Phalangeal Dystrophy.

Definition: a rare autosomal recessive skeletal disorder characterized by a small thorax; brachymelia, predominantly of the rhizomelic type; pelvic abnormalities (hypoplastic iliac wing), and renal anomalies[2]. It has a variable phenotypic expression[3].

Prevalence: 0.14:10,0003,[4] 

Etiology and Pathogenesis: autosomal recessive. It is believed that the locus of the gene associated with Jeune syndrome may be situated on the short arm of chromosome 12[5].

Sonographic findings:

·         Flat, narrow chest (bell-shaped), with short, horizontal ribs associated with short limbs and brachydactyly seem to be the main features. The ribs do not reach more than halfway around the thorax. usually rhizomelic; square-shaped iliac wings2,[6]. The long bone shortening might not become sonographic apparent until 24-26 weeks of gestational age3.

·         Polydactyly is an inconstant feature of Jeune syndrome (approximately 14%)[7]. If present, usually asymmetric and the feet are also affected[8].

·         Thoracopelvic dysplasia should be considered when a low thoracic circumference and abdominal circumference ratio (<0.8) is observed[9].

·         Absence of fetal respiratory movement.

·         The main visceral abnormality is cystic dysplastic renal disease, which is progressive and not usually apparent before birth, althought association with oligohydramnios has been described3. If renal dysplasic disease is not found, polyhydramnios can appear.

·         Jeune should be thought of prospectively among the numerous cases of increased nuchal translucency with normal standard karyotype.

·         Associated anomalies are numerous as described later.

·         Prenatal diagnosis has been reported as early as 16 - 18 weeks of gestational age especially in cases of family history2,7.

Case:

The fairly normal limbs length (note the angulation of the femur and humerus). 

 

Short ribs causing a small chest

 

  

Normal spine (different from thanatophoric dysplasia)

An incidental cord cyst.

The narrow chest 

Differential diagnosis:

Ellis-van Creveld syndrome (chondro-ectodermal dysplasia):

  • Autosomal recessive (short arm of chromosome 4) skeletal dysplasia;

·         Characterized by short limbs, short ribs, postaxial polydactyly of the hands (feet are uncommonly affected8), dysplastic nails and teeth, peculiar upper lip;

·         50[10]-60% have a congenital heart disease (most commonly single atrium)[11].

·         The majority of survivors are of normal intelligence[12].

Short-rib polydactyly syndromes:

  • descriptive category for a group of lethal skeletal dysplasias characterized by a hypoplastic thorax, short ribs, short limbs, polydactyly and visceral abnormalities6,[13].
  • Recently Ho et al. suggested that the Verma–Naumoff syndrome (type 3 short-rib polydactyly syndrome) and Jeune syndrome are variants of the same genetic disorder[14].

Associated anomalies: Multiple organ anomalies are reported:

  • Associated liver disease: hepatic ductal hypoplasia[15], biliary cirrhosis and extensive fibrosis[16],[17];

·         Pancreatic cysts[18] and pancreatic fibrosis10,12;

·         Hirschsprung disease[19];

·         Agenesis of the corpus callosum, Dandy-Walker malformation15 and ventriculomegaly10;

·         Situs inversus10,12;

·         Single umbilical artery, polyhydramnios10,18;

·         Renal glomerular sclerosis12;

·         Increased nuchal translucency[20];

·         Visual loss and night blindness[21] (retinal degeneration);

·         Mild mental retardation12,[22];

·         Hypoplastic hair and skin, oligodontia22;

·         Cleft lip and/or palate3,[23].

Histopathology: Yang et al.[24] suggested 2 types of Jeune syndrome from clinicopathological examination:

type 1: radiologically: irregular metaphyseal ends,

histopathologically: irregular cartilage bone junction with patchy distribution of

physeal zone of hypertrophy;

            type 2: radiologically: smooth metaphyseal ends,
            histopathologically: diffusely retarded and disorganized physes with smooth 
            cartilage bone junctions.

Prognosis: 70% have a fatal outcome in the neonatal period10,11. Lung hypoplasia due to a small thoracic cage, causes often a fatal respiratory failure12,[25]. However surgical thoracic expansion (with methyl-methacrylate prosthesis) has been used successfully in some patients[26],[27].

Patients who survive respiratory failure may have an improvement in the relative growth of the thoracic cage and might have slight to moderate shortness of stature. In the other hand these survivors frequently may suffer from severe renal involvement, leading to renal insufficiency10,[28]. Amirou et al. reported a case of successful renal transplantation in a 10-year-old boy with Jeune syndrome28.

Progressive hepatic dysfunction appears16 and may contribute to a poor long-term prognosis.

Survival to the fourth decade has occurred12.

Recurrence risk: autosomal recessive: 25%

Management: Termination of pregnancy can be offered before viability. Postnatal confirmation of the diagnosis is important for genetic counseling and future pregnancies.

Reviewers: Fernando Heredia, MD; Luc Gourand, MD.


[1] Jeune M, Beraud C, Carron R. Dystrophie Thoracique asphyxiante de caractère familial. Arch Fr Pediatr 1955;12:886

[2] Schinzel A, Savoldelli G, Briner J, Schubiger G. Prenatal sonographic diagnosis of Jeune syndrome. Radiology 1985;154(4):777-8

[3] Twining P, McHugo JM, Pilling DW. Textbook of Fetal Abnormalities. Churchill Livingstone, 2000. pp 254-5.

[4] Callen PW. Ultrasonography in obstetrics and gynecology. Wb. Saunders,  4th edition, 2000. The fetal musculoskeletal system. pp  359

[5] Nagai T, Nishimura G, Kato R, Hasegawa T, Ohashi H, Fukushima Y. Del(12)(p11.21p12.2) associated with an asphyxiating thoracic dystrophy or chondroectodermal dysplasia-like syndrome. Am J Med Genet 1995;55(1):16-8

[6] Benacerraf B. Ultrasound of fetal syndromes. Churchill Livingstone, 1998. pp 181-2.

[7] Lipson M, Waskey J, Rice J, Adomian G, Lachman R, Filly R, Rimoin D. Prenatal diagnosis of asphyxiating thoracic dysplasia. Am J Med Genet 1984 Jun;18(2):273-7

[8] OMIM database 208500

[9] Hsieh YY, Hsu TY, Lee CC, Chang CC, Tsai HD, Tsai CH. Prenatal diagnosis of thoracicopelvic dysplasia. A case report. J Reprod Med 1999;44(8):737-40

[10] Tongsong T, Chanprapaph P, Thongpadunggroj T. Prenatal sonographic findings associated with asphyxiating thoracic dystrophy (Jeune syndrome). J Ultrasound Med1999;18:573-6

[11] OMIM database #225500

[12] Jones KL. Smith’s recognazible patterns of human malformation. 5th edition, 1997. Jeune thoracic dystrophy. pp 340-1.

[13] OMIM database 263530

[14] 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. Am J Med Genet 2000 Feb 14;90(4):310-4
[15] Trabelsi M, Hammou-Jeddi A, Kammoun A, Bennaceur B, Gharbi HA. Asphyxiating thoracic dysplasia associated with hepatic ductul hypoplasia, agenesis of the corpus callosum and Dandy-Walker malformation.  Pediatrie 1990;45(1):35-8
[16] Labrune P, Fabre M, Trioche P, Estournet-Mathiaud B, Grangeponte MC, Rambaud C, Maurage C, Bernard O. Jeune syndrome and liver disease: report of three cases treated with ursodeoxycholic acid. Am J Med Genet 1999;87(4):324-8

[17] Whitley CB, Schwarzenberg SJ, Burke BA, Freese DK, Gorlin RJ. Direct hyperbilirubinemia and hepatic fibrosis: a new presentation of Jeune syndrome (asphyxiating thoracic dystrophy). Am J Med Genet Suppl 1987;3:211-20

[18] Hopper MS, Boultbee JE, Watson AR. Polyhydramnios associated with congenital pancreatic cysts and asphyxiating thoracic dysplasia. A case report. S Afr Med J 1979;56(1):32-3

[19] Aurora P, Wallis CE. Jeune syndrome (asphyxiating thoracic dystrophy) associated with Hirschsprung disease.Clin Dysmorphol 1999 Oct;8(4):259-63

[20] Ben Ami M, Perlitz Y, Haddad S, Matilsky M Increased nuchal translucency is associated with asphyxiating thoracic dysplasia. Ultrasound Obstet Gynecol 1997 Oct;10(4):297-8

[21] Casteels I, Demandt E, Legius E. Visual loss as the presenting sign of Jeune syndrome. Europ J Paediatr Neurol 2000;4(5):243-7
[22] Nagai T, Nishimura G, Kato R, Hasegawa T, Ohashi H, Fukushima. Y Del(12)(p11.21p12.2) associated with an asphyxiating thoracic dystrophy or chondroectodermal dysplasia-like syndrome. Am J Med Genet 1995;55(1):16-8

[23] Fleischer AC, Manning FA, Jeanty P, Romero R. Sonography in Obstetrics and Gynecology: Principles and Practice. Appleton &Lange, 5th edition, pp 472.

[24] Yang SS, Langer LO Jr, Cacciarelli A, Dahms BB, Unger ER, Roskamp J, Dinno ND, Chen H. Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrome spectrum: a clinicopathologic study.

Am J Med Genet Suppl 1987;3:191-207

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