Antley-Bixler syndrome

Philippe Jeanty, MD, PhD Luiz Eduardo Machado, MD Renato Ximenes, MD

*Centro de Treinamento em Diagnóstico por Imagem, Salvador – Bahia – Brasil #Centrus, Campinas, Brazil

Synonyms:   Trapezoidocephaly-synostosis syndrome, multisynostotic osteodysgenesis with long bone fractures.

Definition:   The Antley-Bixler syndrome is a rare disorder which includes musculoskeletal, craniofacial, and urogenital anomalies. The most common skeletal anomalies are radiohumeral synostosis, craniosynostosis, multiple joint contractures, arachnodactyly, femoral and ulnar bowing, camptodactyly, synostoses of carpal and tarsal bones, clubfoot, and vertebral body anomalies. The facial anomalies include: midface hypoplasia often with choanal stenosis or atresia, proptosis, a "pear-shaped nose", and dysplasic ears.

Case report:  see Case 32

This 32 year-old G2P0 patient recently delivered a newborn that died elsewhere with multiple malformations. Typical images of the examination of the current pregnancy are shown below. During the examination the fetus did not move much and the flexion of the elbows remained constant. When the mother saw the 3D images (obtained with an Aloka SSD1700 Dynaview II), she said: “This baby is the same as my first baby !”.

Note the exophtalmia/proptosis, the low nasal bridge, the alteration of the cranial contour at the level of the coronal suture (craniosynostosis)....


and in those beautiful 3D images, the micrognathia, brachycephaly, low set ears. Although this was not appreciable from the static images we also knew that the fetus kept his elbows in a flexed position, suggesting that this was a localized joint anomaly, not a generalized anomaly as would exist in the arthrogryposes.


The fetus survived 15 minutes. Note the chest hypoplasia.


Note the similarity with the images presented in Smith's Recognizable patterns of Human Malformation [1]

History:  First reported in 1975 by Antley and Bixler

Prevalence:   Rare, less than 30 cases up to date. The count is made difficult by the fact that several cases have been reported twice in the literature in different journals but by the same authors ( [2] ,22 ), (,20 ) and ( [4] ,18 ) or may have been reincluded in subsequent publications ( [5] , [6] ).

Etiology:  Autosomal recessive.

Pathogenesis:   Several pathogenesis have been suggested:

  • A few cases have been possibly linked to congenital adrenal hyperplasia associated with pregnancy luteoma
[7] [10] [11] [12] [14]

Sonographic findings:

The cardinal findings include the midfacial hypoplasia, craniosynostosis and the radiohumeral synostosis. Sonographic and other findings are listed in the table below [15] ,, [17] ,:




·        Craniosynostosis

·        Brachycephaly

·        Frontal bossing


·        Proptosis of the eyes (=exophtalmos)

·        Anteverted nostrils

·        Choanal atresia or stenosis

·        Midface hypoplasia


·        Synostosis of the radius & humerus and less commonly the ulna and humerus

·        Narrow rib cage

·        Bowing of the femur / ulna

·        Arachnodactyly with bulbous finger tip

·        Camptodactyly

·        Club-feet

·        Hypoplasia of the body of the scapula [19]

·        Multiple contractures


·        Cardiac defects

·        Imperforate anus

·        Urogenital anomalies (ambiguous genitalia)

The prenatal diagnosis was made several times3 ,16 ,.

Differential diagnosis:  Many of the syndromes with craniosynostosis such as Crouzon and Pfeiffer have similar appearances.

Associated anomalies: See table above. There is one case with associated trisomy 21 [21] .

Prognosis:   One third of affected children are alive, and some have had quite satisfactory development. Some patients with the syndrome have normal intelligence, which suggests a normally developing brain.

Recurrence risk:  25%

Management:   Early survival depends in the release of the upper airway obstruction. Longer-term survival depends on the severity of associated malformations. Cranial vault remodeling to relieve craniosynostosis is important for the prevention of mental impairment22 , [23] , [24] .

Support groups:

FACES: The National Craniofacial Association

The Children's Craniofacial Association


[1] Jones (Ed.) Antley-Bixler syndrome in Smith's Recognizable patterns of Human Malformation p 378

[2] Bottero L, Cinalli G, Labrune P, Lajeunie E, Renier D Antley-Bixler syndrome. Description of two new cases and a review of the literature. Childs Nerv Syst 1997 May;13(5):275-80

[3] Savoldelli G, Schinzel A Prenatal ultrasound detection of humero-radial synostosis in a case of Antley-Bixler syndrome. Prenat Diagn 1982 Jul;2(3):219-23

[4] Butler MG, Hassell S, Feingold M, Tunnessen WW Jr Picture of the month. Antley-Bixler syndrome. Am J Dis Child 1991 Jun;145(6):701-2

[5] Yasui Y, Yamaguchi A, Itoh Y, Ueke T, Sugiyama K, Wada Y The first case of the Antley-Bixler syndrome with a consanguinity in Japan. Jinrui Idengaku Zasshi 1983 Sep;28(3):215-20

[6] Suzuki K, Kanda Y, Sugiyama K, Katoh T, Wada Y, Yasui Y Antley-Bixler syndrome in a sister and brother. Jinrui Idengaku Zasshi 1987 Sep;32(3):247-52

[7] Warmann S, Roth C, Gluer S, Fuchs J Congenital adrenal hyperplasia associated with maternal pregnancy luteoma and the Antley-Bixler syndrome. J Pediatr Surg 2000 Mar;35(3):528-30

[8] Roth C, Hinney B, Peter M, Steinberger D, Lakomek M Features of Antley-Bixler syndrome in an infant born to a mother with pregnancy luteoma. Eur J Pediatr 2000 Mar;159(3):189-92

[9] Zhang Y, Gorry MC, Post JC, Ehrlich GD Genomic organization of the human fibroblast growth factor receptor 2 (FGFR2) gene and comparative analysis of the human FGFR gene family. Gene 1999 Apr 1;230(1):69-79

[10] Chun K, Siegel-Bartelt J, Chitayat D, Phillips J, Ray PN FGFR2 mutation associated with clinical manifestations consistent with Antley-Bixler syndrome Am J Med Genet 1998 May 18;77(3):219-24.

[11] Okajima K, Robinson LK, Hart MA, Abuelo DN, Cowan LS, Hasegawa T, Maumenee IH, Wang Jabs E Ocular anterior chamber dysgenesis in craniosynostosis syndromes with a fibroblast growth factor receptor 2 mutation. Am J Med Genet 1999 Jul 16;85(2):160-70

[12] Gorlin RJ Patient described by Chun et al. may not present Antley-Bixler syndrome. Am J Med Genet 1999 Mar 5;83(1):64

[13] Reardon W, Smith A, Honour JW, Hindmarsh P, Das D, Rumsby G, Nelson I, Malcolm S, Ades L, Sillence D, Kumar D, DeLozier-Blanchet C, McKee S, Kelly T, McKeehan WL, Baraitser M, Winter RM Evidence for digenic inheritance in some cases of Antley-Bixler syndrome? J Med Genet 2000 Jan;37(1):26-32

[14] Pursley TJ, Blomquist IK, Abraham J, Andersen HF, Bartley JA Fluconazole-induced congenital anomalies in three infants. Clin Infect Dis 1996 Feb;22(2):336-40

[15] Kitoh H, Nogami H, Oki T, Arao K, Nagasaka M, Tanaka Y Antley-Bixler syndrome: a disorder characterized by congenital synostosis of the elbow joint and the cranial suture. J Pediatr Orthop 1996 Mar-Apr;16(2):243-6

[16] LeHeup BP, Masutti JP, Droulle P, Tisserand J The Antley-Bixler syndrome: report of two familial cases with severe renal and anal anomalies. Eur J Pediatr 1995 Feb;154(2):130-3

[17] Poddevin F, Delobel B, Courreges P, Bayart M Antley-Bixler syndrome: case report and review of the literature. Genet Couns 1995;6(3):241-6

[18] Hassell S, Butler MG Antley-Bixler syndrome: report of a patient and review of literature. Clin Genet 1994 Nov;46(5):372-6

[19] Mortier GR, Rimoin DL, Lachman RS The scapula as a window to the diagnosis of skeletal dysplasias. Pediatr Radiol 1997 May;27(5):447-51

[20] Schinzel A, Savoldelli G, Briner J, Sigg P, Massini C Antley-Bixler syndrome in sisters: a term newborn and a prenatally diagnosed fetus. Am J Med Genet 1983 Jan;14(1):139-47

[21] Feigin E, Udassin R, Seror D, Szold A, Ben Neriah Z, Glick B Antley-Bixler syndrome and esophageal atresia in a patient with trisomy 21. Clin Genet 1995 Jan;47(1):53-5

[22] Bottero L, Cinalli G, Labrune P, Lajeunie E, Marchac D, Renier D Antley-Bixler syndrome. Description of two new cases and review of the literature. Prognostic and therapeutic aspects. Ann Chir Plast Esthet 1997 Feb;42(1):48-55

[23] LeBard SE, Thiemann LJ Antley-Bixler syndrome: a case report and discussion. Paediatr Anaesth 1998;8(1):89-91

[24] Lauritzen C, Friede H, Elander A, Olsson R, Jensen P Dynamic cranioplasty for brachycephaly. Plast Reconstr Surg 1996 Jul;98(1):7-14

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