• Users Online: 438
  • Print this page
  • Email this page


 
 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 8  |  Issue : 2  |  Page : 109-116

Craniofacial syndromes: Literature review and a proposed classification


Department of Oral and Maxillofacial Surgery, Lady Hardinge Medical College and SSK Hospital, New Delhi, India

Date of Submission22-Jan-2022
Date of Decision14-Feb-2022
Date of Acceptance26-Jul-2022
Date of Web Publication2-Sep-2022

Correspondence Address:
Jaspreet Kaur Deo
Department of Oral and Maxillofacial Surgery, Lady Hardinge Medical College and SSK Hospital, Connaught Place, New Delhi - 110 001
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jigims.jigims_9_22

Rights and Permissions
  Abstract 


Syndromes can potentially affect every part of the craniofacial system. While they have been described individually in the literature, there is lack of a classification system encompassing the entities affecting the craniofacial region. The purpose of this review was to provide clinicians an approach to categorize syndromes according to the morphostructural characteristics, which can aid in diagnostic ease and treatment planning.

Keywords: Classification, craniofacial, syndrome


How to cite this article:
Deo JK. Craniofacial syndromes: Literature review and a proposed classification. J Indira Gandhi Inst Med Sci 2022;8:109-16

How to cite this URL:
Deo JK. Craniofacial syndromes: Literature review and a proposed classification. J Indira Gandhi Inst Med Sci [serial online] 2022 [cited 2022 Oct 2];8:109-16. Available from: http://www.jigims.co.in/text.asp?2022/8/2/109/355325




  Introduction Top


The term “syndrome,” derived from Greek, is defined as a group of clinical signs and symptoms occurring together, characterizing a particular condition.[1] Over 2700 syndromes have been described in the literature with newer ones being recognized over a passing time.[2] Syndromes can be congenital and acquired. Congenital syndromic anomalies affect 0.02–0.03% of all newborns.[3]

Craniofacial growth is a complex phenomenon involving the fusion of several embryonic processes (frontonasal, median nasal, lateral nasal, maxillary, and mandibular) as well as mesodermal and neural crest cell migration. This entire framework rests on underlying genetic pathways involving a dynamic interplay of the individual processes. Isolated gene defects can alter these pathways, leading to maldevelopment of the brachial arches, and the level of involvement determines the severity of presentation. These deformities can be caused by a variety of etiological factors, including chromosomal aberrations, specific gene mutations, and teratogens [Figure 1].[4]
Figure 1: Etiology of craniofacial deformities

Click here to view


Chromosomal aberrations such as trisomy, mosaicism, and translocation have been linked to specific syndromes. Gene mutations have been linked to the specific syndromes including fibroblast growth factor receptor (FGFR) 1, FGFR2, FGFR3, PTCH, keratin16, keratin17, GNAS1, SH3BP2, cystic fibrosis transmembrane conductance regulator, homeostatic iron regulator (HFE), etc.[5],[6],[7],[8] A wide range of human teratogens capable of causing congenital abnormalities during the organogenesis period have been identified including drugs (angiotensin-converting enzyme inhibitors, anticonvulsants, cyclosporin, methotrexate, tetracycline, thalidomide, warfarin, etc.), substance abuse (alcohol, smoking, cocaine, lysergic acid diethylamide, etc.), heavy metals (lead, mercury, etc.), radiation, maternal illness (Cushing's syndrome, hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypothyroidism, insulin-dependent diabetes mellitus, obesity, etc.), and intrauterine infections (syphilis, rubella, cytomegalovirus, etc.).[9] Maternal periconceptional smoking increases the risk of congenital malformations by 13%.[10]

Syndromes can have different types of inheritance patterns which include:[11],[12]

  1. Monogenic


  2. 1.1 Autosomal (dominant or recessive)

    1.2 X-linked (dominant or recessive)

    1.3 Y-linked

    1.4 Mitochondrial

  3. Chromosomal (deletion/duplication/nondisjunction/inversion/translocation)
  4. Complex or multifactorial inheritance.


The exact etiology is yet unknown for many syndromes. However, concurrent advancements in cytogenetics and molecular biology have helped delineate these entities. The spectrum of morphological severity ranges from mild as seen in lip pits to severe craniosynostosis, leading to perinatal mortality.

Several classifications have proposed for individual craniofacial deformities such as Kaban and Pruzansky (1988),[13] and OMENS (1991) classification[14] for Hemifacial microsomia, and Tessier classification (1976) for craniofacial clefts.[15] Craniofacial syndromes have also been briefly described as those involving gingivodental tissues, branchial arches, orofacial clefts, and unusual facies.[16] However, a comprehensive classification system is lacking. Hence, this article attempts to comprehensively include syndromes based on clinical features in the craniofacial region and provides a nonexhaustive list of entities of each subtype.


  Classification Top


Syndromes involving the craniofacial region can be primarily divided into those affecting the soft and hard tissue. The classification focuses on the morphostructural craniofacial findings of the conditions. There can be syndromes affecting both the soft and hard tissue, as the underlying bony architectural defects manifest in deformities of the soft-tissue drape. The present classification is an attempt to simplify the understanding of these syndromes based on their key clinical findings.

Syndromes affecting the soft tissue

Syndromes affecting the craniofacial soft tissue involve the lip, tongue, salivary gland, orbit, skin–mucous membranes, and nervous and vascular systems [Figure 2].
Figure 2: Classification of craniofacial syndromes affecting the soft tissues

Click here to view


Failure of fusion of the embryonic facial processes produces median/paramedian orofacial clefts, which may involve the underlying hard tissue as well. About 36% of the orofacial clefts are syndromic.[17] True median cleft lip is rare with an incidence of 0.17%–0.61%[18],[19] and is associated with Majewski syndrome, Mohr syndrome (oral-facial-digital syndrome [OFDS] Type II), and Pai syndrome.[20],[21] Syndromes such as median facial dysplasia and van der Woude can present with bilateral or unilateral cleft lip. Popliteal pterygium syndrome manifests as popliteal webs, genitourinary anomalies, orofacial clefts, and lower lip pits.[22]

Lip pits are congenital sinuses manifesting commonly in the vermillion of the lower lip with or without discharge.[23] Van der Woude or lip pits syndrome consists of lip pits with or without cleft lip and palate. It is the most common facial cleft syndrome[24] and has been associated with interferon regulatory factor-6 gene mutation[25] and microdeletion at chromosome bands 1q32-q41.[26] Indications for surgical intervention include esthetics and chronic inflammation.[27]

Cheilitis granulomatosa or Miescher's syndrome is a chronic swelling of the lips due to histamine or bradykinin-mediated plasma leakage in the subcutaneous tissue. When associated with recurrent facial palsy and plicated tongue, it is termed as Melkersson-Rosenthal syndrome. It may be a manifestation of Crohn's disease, sarcoidosis, or orofacial granulomatosis.[28]

Malformations of the tongue have been previously classified as aglossia, microglossia, macroglossia, hemiatrophy, hemihypertrophy, long tongue, ankyloglossia, cleft or bifid tongue, and syndromes that cannot be classified in a special condition.[29] The tongue can have deep grooves on the dorsal surface which may be painless or associated with burning sensation, referred to as fissured tongue in Down's syndrome, Melkersson-Rosenthal syndrome, etc.[30]

Ankyloglossia (tongue-tie) is a consistent finding in PRS, OFDS, Meckel syndrome, Patau syndrome, Robinow Syndrome, short rib syndrome, alpha-thalassemia mental retardation Syndrome, Fraser Syndrome, and Wiedemann-Beckwith syndrome, wherein the lingual frenum is attached to the tip of the tongue or just distal to it, posing difficulty during breastfeeding and speech articulation. Management includes frenectomy and speech therapy.[31] Bilobed or bifid tongue can be associated with OFDS, Opitz G/BBB Syndrome, Klippel-Feil anomaly, and Larsen syndrome.[32],[33],[34],[35]

Macroglossia (enlarged tongue) can be true or relative, presenting with feeding and swallowing difficulties, anterior open bite, prognathism, increased ramus to body angle, articulation errors with consonants, and upper airway obstruction.[36],[37] True macroglossia due to tissue overgrowth is seen in Beckwith-Wiedemann syndrome, cardiofaciocutaneous (CFC) syndrome, Klippel-Trenaunay-Weber syndrome, Simpson-Golabi-Behmel syndrome, Laband syndrome, Marfan syndrome, Tollner syndrome, Costello syndrome, Sotos syndrome, Perlman syndrome, and chromosomal abnormalities (4p deletion, 11p duplication, 17p11.2 deletion, and 9q34 deletion). Down syndrome can exhibit true or relative macroglossia.[38]

Maxillofacial trauma can cause orbital injuries, which may result in conditions such as superior orbital fissure syndrome (Rochon-Duvigneaud syndrome), orbital apex syndrome, and orbital compartment syndrome. Superior orbital fissure and orbital apex syndrome are caused due to compression of contents of the superior orbital fissure and optic canal, respectively. This results in ophthalmoplegia, pupillary dilation, ptosis, impaired direct pupillary reflex, loss of accommodation, and even blindness. Orbital compartment syndrome occurs due to acute rise in the intraocular pressure, secondary to retrobulbar hemorrhage, or displaced fracture segments. This is a surgical emergency requiring immediate decompression of the orbital contents.[39] Horner syndrome is a tetrad of miosis, anhidrosis, ptosis, and enophthalmos, which may be congenital or acquired, caused due to disruption of the oculosympathetic pathway.[40]

Vascular malformations can be arterial, venous, lymphatic, capillary, or combined. Syndromes associated with low-flow malformations include Adams-Oliver, blue rubber bleb nevus, Cutis marmorata telangiectatica congenita, Gorham-Stout, Klippel-Trénaunay, Maffucci, Proteus, and Sturge-Weber syndromes (SWS), whereas Cobb, Cowden, Ehlers-Danlos (Type 4), Osler-Weber-Rendu, Parkes Weber, and Wyburn-Mason syndromes demonstrate high flow. SWS is a congenital sporadic condition characterized by port-wine stain and vascular malformations of the leptomeninges and eye. Klippel-Trenaunay syndrome is characterized by a superficial vascular stain of the skin with soft tissue and bony hypertrophy of the affected limb, and varicose veins with or without deep venous anomalies. Proteus syndrome, coined by Weidemann, Burgio, and Aidenhoff in 1983, is characterized by hemihypertrophy of the hands and feet, exostosis, cranial hyperostosis, vascular anomalies, and epidermal nevi.[41],[42]

Syndromes involving the skin and mucous membranes can present with oral lichen planus, aphthous ulcers, hyperpigmented macules, and vesiculobullous lesions. Grinspan's syndrome is a triad of diabetes mellitus, hypertension, and oral lichen planus. Behcet's syndrome is a tetrad of uveitis, conjunctivitis, recurrent aphthae, and genital ulcers. CFC syndrome presents with distinct facial features (increased facial width, ptosis, and relative macrocephaly), cardiac abnormalities, intellectual disability, and cutaneous lesion (nevi, hemangiomas, xerosis, hyperkeratosis, and eczema). It is a part of RASopathies mediated by gene mutations in the Ras/mitogen-activated protein kinase pathway, which include Noonan syndrome and Costello syndrome as well.[43] Sweet syndrome is acute febrile neutrophilic dermatosis characterized by sudden onset fever and erythematous plaques.[44] Peutz-Jeghers syndrome is an autosomal dominant condition characterized by the association of small intestine hamartomatous polyps, hyperpigmented macules (eyes, nostrils, perianal area, and buccal mucosa), and predisposition for cancer.[45]

Syndromes affecting the salivary glands can produce hyper- or hypo-secretions owing to enlargement or aplasia. Sjögren's syndrome is an autoimmune disorder consisting of keratoconjunctivitis sicca, xerostomia, parotid enlargement, and association with diseases like SLE, rheumatoid arthritis, etc., It is linked with HLA-DR3 and HLA-B8.[46]

Syndromes affecting the hard tissue

The hard-tissue component is subdivided into conditions afflicting the maxilla, mandible, or both. There may be excess or deficiency of either jaw, which can be true, or relative. Excess can be due to forward and downward positioning or enlarged size, while deficiency can be due to retropositioning or micrognathia. This discrepancy can be skeletal, dental, or combined, manifesting in a single (vertical, sagittal, or transverse) or multiple facial planes. Separate divisions categorize syndromes associated with cyst and tumors and conditions affecting the dentition [Figure 3].
Figure 3: Classification of craniofacial syndromes affecting the hard tissues

Click here to view


Syndromes affecting the midface

Midface excess

Human phenotype ontology describes midfacial excess as an abnormal anterior positioning of the infraorbital and perialar regions, increased nasolabial angle, or increased convexity of the face. Syndromes with this feature include Seckel 10 and Troyer syndrome.[47]

Seckel syndrome 10 is an autosomal recessive, microcephalic osteodysplastic dwarfism disorder with mental retardation, bird-like facies, and insulin resistance.[48] Troyer syndrome is a recessive familial spastic paraplegia with distal muscle wasting, named after the family in which it was first identified. Its features include but are not limited to, mental disability, dysdiadokinesia, midface hyperplasia, pes cavus, and nystagmus.[49]

Midface deficiency

Midface retrusion is a decreased projection of the midfacial structures due to hypoplasia or retroposition. At least 218 conditions show this feature as a consistent clinical finding.[50]

Syndromes associated with CLP/CP have a failure of fusion of the embryonic facial processes, resulting in different types of orofacial clefts. Based on a tri-center study, the incidence of CLP was 0.93/1000, and CP alone was 0.17/1000 in India, effectively meaning an infant is born with orofacial cleft every 20 min in the country.[51] Repair of the palatal defect causes fibrosis, which restricts the maxillary growth in the transverse and sagittal planes. Patients may have a concave facial profile with dish-face deformity, depressed malar arches, Class III malocclusion, anterior crossbite, and impacted and supernumerary teeth. Over 250 syndromes have been identified, wherein facial clefts are the primary feature. Some of these syndromes include Bamforth-Lazarus, Bartsocas-Papas, Binder, Branchio-oculo-facial, CHARGE, Cornelia de Lange, DiGeorge, Gorlin, Kabuki, Kallmann, Loeys-Dietz, Stickler, Miller, Siderius X-linked mental retardation, Median facial dysplasia, Fetal hydantoin, Fetal trimethadione, etc.[52] Median facial dysplasia is characterized by midline facial deficiencies, which may involve the corpus callosum. The compromised development of the midface results in very early dish face and severe maxillary hypoplasia.[53] Binder syndrome, also called nasomaxillary hypoplasia, was first described by Binder in 1962. It comprises arhinoid facies, reduced or absent nasal spine, maxillary hypoplasia, nasal and frontal sinus atrophy.[54]

Early sutural fusion or decreased activity of the growth centers due to FGFR gene mutation results in craniosynostosis syndromes. The FGFR gene encodes the tyrosine kinase receptor, which activates the RAS/MAPK, PI3K/AKT, and PKC pathways. These pathways regulate cell proliferation, differentiation, morphogenesis, and migration.[55] These encompass Apert, Antley-Bixler, Beare-Stevenson cutis gyrata, Crouzon, Jackson-Weiss, Bent Bone Dysplasia, Saethre-Chotzen, Muenke, and Pfeiffer syndrome. The cranial phenotype is determined by the onset and number of sutures involved.[6] Crouzon syndrome is an autosomal dominant disorder characterized by craniosynostosis, shallow orbits with proptosis, maxillary hypoplasia, cleft palate, or bifid uvula. Apert syndrome presents as midface hypoplasia, bicoronal synostosis, and complex syndactyly of the upper and lower limbs.[6],[55]

Syndromes affecting the mandible

Mandibular excess

Mandibular prognathia is an abnormally forward projection of the mandible in relation to the cranial base. The deformity is termed as the Habsburg jaw, after the Spanish Habsburg royal family who shared this distinctive trait.[56] Nearly 140 conditions exhibit this feature.[57]

Patients present with masticatory difficulties and reverse overjet due to a mainly horizontal growth pattern. Their definitive management includes orthognathic setback procedures such as sagittal split osteotomy, vertical ramus osteotomy, and genioplasty. Large discrepancies of over 6–8 mm are managed using bi-jaw procedures which bring the maxilla forward simultaneously.

Mandibular deficiency

Patients with mandibular deficiency present with retrognathia, bird-like facies, Angle Class II malocclusion, increased overjet, and upper airway obstruction. Pierre Robin sequence, hemifacial microsomia, Goldenhar syndrome, Moebius syndromes, Nager syndrome, DiGeorge syndrome, and Treacher Collins syndrome exhibit this feature.

Pierre Robin sequence is a triad of micrognathia, glossoptosis, and cleft palate. Hemifacial microsomia and Goldenhar syndrome are part of the spectrum of oculo-auriculo-vertebral syndromes. These have been classified by Kaban, Pruzansky, and others based on the severity of the clinical findings. Pathologic dysregulation of the first and second branchial arches can cause hypoplasia of the midface, temporomandibular joint, orbits, ears, and overlying soft tissue. Treacher Collins syndrome is an autosomal dominant disorder associated with mutation of Treacle Ribosome Biogenesis Factor 1 gene. Moebius syndrome is characterized by mask-like facies and cranial nerve palsy (III, IV, V, VI, VII, IX, X, XII).[58]

Management includes the advancement of the mandible using functional appliances in the growth phase, orthognathic procedures, and distraction osteogenesis, following completion of growth spurts.

Syndromes associated with cyst and tumors

Syndromes associated with nonodontogenic cysts include Gardner syndrome and Hyperparathyroidism-jaw tumor syndrome, while odontogenic cysts include cleidocranial dysplasia, Maroteaux–Lamy syndrome, and Gorlin–Goltz syndrome.

Syndromes affecting the dentition

Syndromes can be associated with specific dental features such as taurodontism, talon cusp, impacted/supernumerary/missing teeth, and delayed/premature eruption of teeth.


  Conclusion Top


The management of syndromes is multidisciplinary and requires the involvement of a maxillofacial surgeon, orthodontist, pedodontist, endocrinologist, dermatologist, pediatrician, general surgeon, neurosurgeon, physiotherapist, and speech therapist. There is an overlap in the manifestations of several syndromes; however, specific findings set them apart from each other. While there have been several attempts to encompass this ever-expanding legion of entities, this paper brings them together in a morphostructural manner.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
”Syndrome.” Merriam-Webster.com Dictionary, Merriam-Webster. Available from: https://www.merriam-webster.com/dictionary/syndrome. [Last accessed on 2021 Apr 05].  Back to cited text no. 1
    
2.
Mandell HN. Dictionary of medical syndromes. JAMA 1990;264:2940.  Back to cited text no. 2
    
3.
Craniofacial Anomalies and Associated Birth Defects. Global Registry and Database on Craniofacial Anomalies. Report of a WHO Registry Meeting on Craniofacial Anomalies. Available from: https://www.who.int/genomics/anomalies/en/Chapter02.pdf. [Last accessed on 2021 Apr 05].  Back to cited text no. 3
    
4.
Cohen MM Jr. The Child with Multiple Birth Defects. 2nd ed. New York: Oxford University Press; 1997.  Back to cited text no. 4
    
5.
Genetic Alliance; District of Columbia Department of Health. Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Appendix G, Single-Gene Disorders. Washington (DC): Genetic Alliance; 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK132154. [Last accessed on 2021 Oct 08].  Back to cited text no. 5
    
6.
Wenger T, Miller D, Evans K. FGFR Craniosynostosis Syndromes Overview. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle. 1998. [updated 2020 Apr 30]. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK1455/. [Last accessed on 2021 Apr 05].  Back to cited text no. 6
    
7.
McLean WH, Rugg EL, Lunny DP, Morley SM, Lane EB, Swensson O, et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995;9:273-8.  Back to cited text no. 7
    
8.
Bhattacharya S, Mishra RK. Fibrous dysplasia and cherubism. Indian J Plast Surg 2015;48:236-48.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Hall JG, Weksberg R. Pediatric diseases and epigenetics. Medical Epigenetics. Academic Press, 2021. 377-406. [doi: 10.1016/b978-0-12-803239-8.00023-5].  Back to cited text no. 9
    
10.
Leonardi-Bee J, Britton J, Venn A. Secondhand smoke and adverse fetal outcomes in nonsmoking pregnant women: A meta-analysis. Pediatrics 2011;127:734-41.  Back to cited text no. 10
    
11.
Genetic Alliance; the New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. Appendix E, Inheritance Patterns. Washington (DC): Genetic Alliance; 2009. Available from: https://www.ncbi.nlm.nih.gov/books/NBK115561/. [Last accessed on 2021 Oct 08].  Back to cited text no. 11
    
12.
MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US). What are the Different Ways in Which a Genetic Condition Can be Inherited?. [Last updated on 2021 Apr 19]. Available from: https://medlineplus.gov/genetics/understanding/inheritance/inheritancepatterns. [Last accessed on 2021 Oct 08].  Back to cited text no. 12
    
13.
Kaban LB, Moses MH, Mulliken JB. Surgical correction of hemifacial microsomia in the growing child. Plast Reconstr Surg 1988;82:9-19.  Back to cited text no. 13
    
14.
Vento AR, LaBrie RA, Mulliken JB. The O.M.E.N.S. classification of hemifacial microsomia. Cleft Palate Craniofac J 1991;28:68-76.  Back to cited text no. 14
    
15.
Tessier P. Anatomical classification facial, cranio-facial and latero-facial clefts. J Maxillofac Surg 1976;4:69-92.  Back to cited text no. 15
    
16.
Bartzela TN, Carels C, Maltha JC. Update on 13 syndromes affecting craniofacial and dental structures. Front Physiol 2017;8:1038.  Back to cited text no. 16
    
17.
Cohen MM Jr. Syndromes with orofacial clefting. In: Cleft Lip and Palate: From Origin to Treatment. New York: Oxford University Press; 2002. p. 53-65.  Back to cited text no. 17
    
18.
Dube G, Jain S. Prevalence of true median cleft of upper lip as reflected from a small central Indian population: Attempt to report and review the true median cleft of upper lip. J Maxillofac Oral Surg 2018;17:508-13.  Back to cited text no. 18
    
19.
Hamzan MI, Sulaiman WA. True median cleft lip-15 years of review and prevalence. Cleft Palate Craniofac J 2020;57:1051-4.  Back to cited text no. 19
    
20.
Sakai N, Nakakita N, Yamazaki Y, Ui K, Uchinuma E. Oral-facial-digital syndrome type II (Mohr syndrome): Clinical and genetic manifestations. J Craniofac Surg 2002;13:321-6.  Back to cited text no. 20
    
21.
Pai GS, Levkoff AH, Leithiser RE Jr. Median cleft of the upper lip associated with lipomas of the central nervous system and cutaneous polyps. Am J Med Genet 1987;26:921-4.  Back to cited text no. 21
    
22.
Shkoukani MA, Chen M, Vong A. Cleft lip – A comprehensive review. Front Pediatr 2013;1:53.  Back to cited text no. 22
    
23.
Gorlin RJ, Cervenka J. Syndromes of facial clefting. Scand J Plast Reconstr Surg 1974;8:13-25.  Back to cited text no. 23
    
24.
Rintala AE, Ranta R. Lower lip sinuses: I. Epidemiology, microforms and transverse sulci. Br J Plast Surg 1981;34:26-30.  Back to cited text no. 24
    
25.
Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, et al. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nat Genet 2002;32:285-9.  Back to cited text no. 25
    
26.
Schutte BC, Basart AM, Watanabe Y, Laffin JJ, Coppage K, Bjork BC, et al. Microdeletions at chromosome bands 1q32-q41 as a cause of Van der Woude syndrome. Am J Med Genet 1999;84:145-50.  Back to cited text no. 26
    
27.
Guner U, Celik N, Ozek C, Cagdas A. Van der Woude syndrome. Scand J Plast Reconstr Surg Hand Surg 2002;36:103-5.  Back to cited text no. 27
    
28.
Cancian M, Giovannini S, Angelini A, Fedrigo M, Bendo R, Senter R, et al. Melkersson-Rosenthal syndrome: A case report of a rare disease with overlapping features. Allergy Asthma Clin Immunol 2019;15:1.  Back to cited text no. 28
    
29.
Shafer WG, Hine MK, Levy BM. A Text Book of Oral Pathology. Bangalore: Prism Books; 1993. p. 25-6.  Back to cited text no. 29
    
30.
Emmanouil-Nikoloussi E, Kerameos-Foroglou C. Congenital syndromes connected with tongue malformations. Bull Assoc Anat (Nancy) 1992;76:67-72.  Back to cited text no. 30
    
31.
Chaubal TV, Dixit MB. Ankyloglossia and its management. J Indian Soc Periodontol 2011;15:270-2.  Back to cited text no. 31
[PUBMED]  [Full text]  
32.
Mihci E, Tacoy S, Ozbilim G, Franco B. Oral-facial digital syndrome type 1. Indian Pediatr 2007;44:854-6.  Back to cited text no. 32
    
33.
Orhan D, Balci S, Deren O, Utine EG, Başaran A, Kale G. Prenatally diagnosed lethal type Larsen-like syndrome associated with bifid tongue. Turk J Pediatr 2008;50:395-9.  Back to cited text no. 33
    
34.
Parashar SY, Anderson PJ, Cox TC, McLean N, David DJ. Multidisciplinary management of Opitz G BBB syndrome. Ann Plast Surg 2005;55:402-7.  Back to cited text no. 34
    
35.
Widgerow AD. Klippel-Feil anomaly, cleft palate, and bifid tongue. Ann Plast Surg 1990;25:216-22.  Back to cited text no. 35
    
36.
Rizer FM, Schechter GL, Richardson MA. Macroglossia: Etiologic considerations and management techniques. Int J Pediatr Otorhinolaryngol 1985;8:225-36.  Back to cited text no. 36
    
37.
Núñez-Martínez PM, García-Delgado C, Morán-Barroso VF, Jasso-Gutiérrez L. Congenital macroglossia: Clinical features and therapeutic strategies in paediatric patients. Bol Med Hosp Infant Mex 2016;73:212-6.  Back to cited text no. 37
    
38.
Balaji SM. Reduction glossectomy for large tongues. Ann Maxillofac Surg 2013;3:167-72.  Back to cited text no. 38
[PUBMED]  [Full text]  
39.
Bonanthaya K, Panneerselvam E, Manuel S, Kumar VV, Rai A, editors. Oral and Maxillofacial Surgery for the Clinician. Springer Nature; India. 2021.  Back to cited text no. 39
    
40.
Salvesen R. Horner syndrome. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003. p. 648.  Back to cited text no. 40
    
41.
Garzon MC, Huang JT, Enjolras O, Frieden IJ. Vascular malformations. Part II: Associated syndromes. J Am Acad Dermatol 2007;56:541-64.  Back to cited text no. 41
    
42.
Nozaki T, Nosaka S, Miyazaki O, Makidono A, Yamamoto A, Niwa T, et al. Syndromes associated with vascular tumors and malformations: A pictorial review. Radiographics 2013;33:175-95.  Back to cited text no. 42
    
43.
Pierpont ME, Magoulas PL, Adi S, Kavamura MI, Neri G, Noonan J, et al. Cardio-facio-cutaneous syndrome: Clinical features, diagnosis, and management guidelines. Pediatrics 2014;134:e1149-62.  Back to cited text no. 43
    
44.
von den Driesch P. Sweet's syndrome (acute febrile neutrophilic dermatosis) J Am Acad Dermatol 1994;31:535-56.  Back to cited text no. 44
    
45.
McGarrity TJ, Amos CI, Baker MJ. Peutz-Jeghers Syndrome. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle. 2001 [updated 2021 Sep 2]. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK1266/. [Last accessed on 2021 Oct 08].  Back to cited text no. 45
    
46.
Krishnamurthy S, Vasudeva SB, Vijayasarathy S. Salivary gland disorders: A comprehensive review. World J Stomatol 2015;4:56-71.  Back to cited text no. 46
    
47.
NCBI. MedGen, Hyperplasia of Midface. Available from: https://www.ncbi.nlm.nih.gov/medgen/451009. [Last accessed on 2021 Jun 05].  Back to cited text no. 47
    
48.
Ramalingam K, Kaliyamurthy SD, Govindarajan M, Swathi S. Seckel syndrome: A report of a case. J Indian Soc Pedod Prev Dent 2012;30:258-61.  Back to cited text no. 48
[PUBMED]  [Full text]  
49.
Cross HE, McKusick VA. The Troyer syndrome. A recessive form of spastic paraplegia with distal muscle wasting. Arch Neurol 1967;16:473-85.  Back to cited text no. 49
    
50.
NCBI. MedGen, Midface Retrusion. Available from: https://www.ncbi.nlm.nih.gov/medgen/388629. [Last accessed on 2021 Jun 05].  Back to cited text no. 50
    
51.
Mossey P, Little J. Addressing the challenges of cleft lip and palate research in India. Indian J Plast Surg 2009;42 Suppl: S9-18.  Back to cited text no. 51
    
52.
Leslie EJ, Marazita ML. Genetics of cleft lip and cleft palate. Am J Med Genet C Semin Med Genet 2013;163C: 246-58.  Back to cited text no. 52
    
53.
Venkatesh R. Syndromes and anomalies associated with cleft. Indian J Plast Surg 2009;42 Suppl: S51-5.  Back to cited text no. 53
    
54.
Binder KH. Dysostosis maxillo-nasalis, ein archinencephaler missbildungskomplex. Dtsch Zahnarztuche Z 1962;17:438-44.  Back to cited text no. 54
    
55.
Azoury SC, Reddy S, Shukla V, Deng CX. Fibroblast growth factor receptor 2 (FGFR2) mutation related syndromic craniosynostosis. Int J Biol Sci 2017;13:1479-88.  Back to cited text no. 55
    
56.
Turliuc MD, Cucu AI, Perciaccante A, Tosolini G, De Luca S, Costachescu B, et al. Hydrocephalus of King Charles II of Spain, the bewitched king. Eur Neurol 2019;81:76-8.  Back to cited text no. 56
    
57.
NCBI. MedGen, Mandibular Prognathia. Available from: https://www.ncbi.nlm.nih.gov/medgen/98316. [Last accessed on 2021 Jun 05].  Back to cited text no. 57
    
58.
Jenzer AC, Schlam M. Retrognathia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538303/. [Last updated on 2021 Jul 08].  Back to cited text no. 58
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Classification
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed118    
    Printed6    
    Emailed0    
    PDF Downloaded8    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]