Binder Syndrome

Binder syndrome is a congenital condition characterised by hypoplasia of the anterior part of the maxilla and nasal complex (midfacial hypoplasia) resulting in a concave profile with a flat nose and a relative prognatism of the mandible.¹

Nasomaxillary hypoplasia, maxillonasal dysostosis, maxillonasal dysplasia, Binder association, Binder phenotype, Binder type.

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Binder syndrome is an uncommon condition. The condition equally affects both genders.² The incidence is unknown because mild cases may go unnoticed or chondrodysplasia punctate cases are diagnosed as Binder syndrome as the facial abnormalities are quite similar.³

The etiology of Binder syndrome is unknown, but it is likely heterogenic. Disturbance of the development of the nasal septum in the early prenatal period (until 14 weeks of gestation) causes congenital facial anomalies such as Binder phenotype.⁴ Von Binder postulated originally that the structural defects are caused by rhinocephalic dysplasia, which he called ‘maxillonasal dysostosis’.⁵ Quarrell reviewed the clinical features of the disorder and concluded that it does not represent a single nosologic entity but that it has to be considered an association or a phenotype.²
In most cases with Binder syndrome nasal protrusion is more affected than nasal height. The length of the nasal bone is usually normal. The columella is shortened with an absent nasal spine (bony base of columella). There is perialar flatness, the nostrils are horizontal or comma shaped. The upper lip is convex with a stretched and shallow Cupid’s bow. The poor protrusion of the maxilla creates a relative prognatism of the mandible (reverse overbite).
Binder syndrome can occur isolated or be associated with a genetic condition. Chondrodysplasia punctate is the most common associated genetic condition. Some authors consider Binder syndrome as a mild form of chondrodyplasia punctate.⁶ Associations have been described between Binder syndrome and prenatal vitamin K deficiency7^,8, prenatal Warfarine⁹, phenytoin and alcohol exposure^10,11 and maternal autoimmune disease.¹²
 

The facial anomalies in Binder syndrome may be isolated. Possible associated anomalies are skeletal anomalies (especially rhizomelic shortening and cervical spine anomalies.)¹³ Postnatally, hearing impairment, strabismus, nasal mucosa atrophy, hypoplastic frontal sinuses and microdontia of the central upper incisors may become evident. At an older age patients may show hypoplasia of terminal phalangeal of the hand and patchy distortion of vertebrae, a residuum of vertebral clefting.¹ 
There is no proof that Binder syndrome is associated with lower IQ.²
 

Most cases are sporadic, although an autosomal recessive inheritance with reduced penetrance or a multifactorial genetic background is suggested.^{2, 14}

Diagnosis is made on the typical appearance of the face: a concave profile with a flat nose and relative prognatism of the mandible. Three-dimensional rendered ultrasound may be very helpful in recognizing Binder syndrome^8,9,15,16 and three-dimensional multiplanar ultrasound is useful to identifying the exact midsagittal profile view. Objective measurements as an increased naso-frontal angle and a decreased maxillo-nasal mandible angle may support the diagnosis.^{17, 18} MRI may be of help in evaluating the airway, confirming the facial findings and detect cervical spine abnormalities.¹⁹

A typically flat nose is also seen in conditions like chondrodysplasia punctate and Wolff- Hirschhorn syndrome (Greek warrior helmet.)^3,6,17,20 Keutel syndrome and Robinow syndrome share some features with Binder syndrome, such as midfacial hypoplasia.^21,22
Craniosynostose syndromes, frontonasal dysplasia, holoprosencephaly and facial clefts can also give the impression of a flat nose in the profile view.
In many syndromes, like trisomy 21, Pallister Killian syndrome, Stickler syndrome, Robinow syndrome, Aarskog syndrome and skeletal anomalies the phenotype is characterised by a generally small nose.²³ It should be remembered that the shape of the nose is influenced by racial differences and familial traits, especially later in pregnancy.
 

As the phenotype of Binder syndrome is best visible in the profile, care has to be taken to identify the exact midsagittal profile plane. Three-dimensional ultrasound is very useful to evaluate the face and to find the exact midsagittal profile view.^8,9,15,16 When an abnormally flat fetal nose is suspected, the woman should be referred to an expert center for an advanced ultrasound examination to rule out associated anomalies and genetic consultation.

The prognosis for isolated Binder syndrome is good. Adolescents may seek medical attention for cosmetic reasons or orthodontic problems. When Binder syndrome is part of a genetic condition the prognosis is variable and depends on the kind and severity of the underlying condition.

Standard obstetric care is recommended. Amniotic fluid volume should be monitored as polyhydramnios may develop. Postnatal respiratory impairment is not commonly reported but described in some case reports, therefore delivery in a tertiary center is advisable.^11,19

1. Online Mendelian Inheritance in men (OMIM). Bethesda, MD: National Centre for Biotechnology Information, National Library of Medicine. https://www.omim.org. 15505 Maxillonasal dysplasia, Binder type.
2. Quarrell OWJ, Koch M, Hughes HE. Maxillonasal dysplasia (Binder's syndrome). J. Med. Genet 1990;27:384-387.
3. Sheffield L J, Halliday JL, Jensen F. Maxillonasal dysplasia (Binder's syndrome) and chondrodysplasia punctata. (Letter). J Med Genet 1991;28:503-504.
4. Katsube M, Yamada S, Miyazaki R, Yamaguchi Y, Makishima H, Takakuwa T, Yamamoto A, Fujii Y, Morimoto N, Ito T, Imai H, Suzuki S. Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype. Prenatal Diagnosis 2017;37(9):907-915.
5. Binder von KH. Dysostosis maxillo-nasalis, ein arhinencephaler Missbildungskomplex. Deutsche Zahnaerztl Z 1962;17:438-444.
6. Sheffield L J, Halliday JL., Danks DM, Rogers JG, Poulos A, Morrison N Clinical, radiological and biochemical classification of chondrodysplasia punctata. (Abstract). Am J Hum Genet 1989;45 (suppl): A64.
7. Jaillet J, Robert-Gnansia E, Till M, Vinciguerra C, Edery P. Biliary lithiasis in early pregnancy and abnormal development of facial and distal limb bones (Binder syndrome): a possible role for vitamin K deficiency. Birth Defects Res A Clin Mol Teratol 2005;73(3):188-193.
8. Levaillant JM, Moeglin D, Zouiten K, Bucourt M, Burglen L, Soupre V, Baumann C, Jaquemont ML, Touraine R, Picard A, Vuillard E, Belarbi N, Oury JF, Verloes A, Vazquez MP, Labrune P, Delezoide AL, Gérard-Blanluet M. Binder phenotype: clinical and etiological heterogeneity of the so-called Binder maxillonasal dysplasia in prenatally diagnosed cases, and review of the literature. Prenat Diagn 2009;29(2):140-150.
9. Malik R, Agarwal G. Antenatally diagnosed Binder syndrome in newborn following maternal warfarin intake in first trimester. Case report JCR 2016;6(1):36-39. 
10. Leicher-Düber A, Schumacher R, Spranger J. Stippled epiphyses in fetal alcohol syndrome. Pediatr Radiol 1990;20(5):369–370. 
11. Seguin JH, Baugh RF, McIntee RA. Airway manifestations of chondrodysplasia punctate. International Journal of Pediatric Otorhinolaryngology 1993; 27(1);85-90.
12. Colin E, Touraine R, Levaillant JM, Pasquier L, Boussion F, Ferry M, Guichet A, Barth M, Mercier A, Gérard-Blanluet M, Odent S, Bonneau D. Binder phenotype in mothers affected with autoimmune disorders. J Matern Fetal Neonatal Med 2012;25(8):1413-1418.
13. Olow-Nordenram MAK, Radberg CT. Maxillo-nasal dysplasia (Binder syndrome) and associated malformations of the cervical spine. Acta Radiol 1984;25:353-360.
14. Olow-Nordenram M, Valentin J. An etiologic study of maxillo-nasal dysplasia: Binder's syndrome. Scand J Dent Res 1988;96:69-74.
15. Cook K, Prefumo F, Presti F, Homfray T, Campbell S. The prenatal diagnosis of Binder syndrome before 24 weeks of gestation: case report. Ultrasound Obstet Gynecol 2000;16(6):578-581.
16. Cuillier F, Cartault F, Lemaire P, Alessandri JL. Maxillo-nasal dysplasia (Binder syndrome): antenatal discovery and implications. Fetal Diagn Ther. 2005;20:301-305.
17. Jong de-Pleij EAP, Bilardo CM, Manten GTR. Look at the fetal nose 1; the naso-frontal angle. Ultrasound Obstet Gynecol 2017;50:297-298.
18. Jong-Pleij de EAP, Ribbert LSM, Manten GTR, Tromp E, Bilardo CM. Maxilla-nasion-mandible angle: a new method to assess profile anomalies in pregnancy. Ultrasound Obstet Gynecol 2011;37:562-569.
19. Blumenfeld YJ, Davis AS, Hintz SR, Milan K, Messner AH, Barth RA, Hudgins L, Chueh J, Homeyer M, Bernstein JA, Enns G, Atwal P, Manning M. Prenatally Diagnosed Cases of Binder Phenotype Complicated by Respiratory Distress in the Immediate Postnatal Period. J Ultrasound Med 2016;35(6):1353-1358.  
20. Byrne JL, Woodward P, Kennedy A. Prenatal diagnosis of Wolf‐Hirschhorn syndrome (4p‐) by 3D ultrasound. Ultrasound Obstet Gynecol 2012;409:266. 
21. Demirel G, Oguz SS, Celik IH, Erdeve O, Uras N, Dilmen U. A case of Keutel syndrome diagnosed in the neonatal period: associated with Binder phenotype. Genet Couns 2012;23(1):25-30.
22. Mazzeu J, Pardono E, Vianna-Morgante AM, Richieri-Costa A, Ae Kim C, Brunoni D, Martelli L, de Andrade CE, Colin G, Otto PA. Clinical characterization of autosomal dominant and recessive variants of Robinow syndrome. Am J Med Genet A  2007;143(4):320-325.
23. Jones KL. Smith’s Recognizable Patterns of Human Malformation. W.B. Saunders Company: Philadelphia, 1997.

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