Trigonocephaly

Trigonocephaly is a congenital condition of premature fusion of the metopic suture (from Greek metopon, "forehead"), leading to a triangular forehead. The merging of the two frontal bones leads to transverse growth restriction and parallel growth expansion. It may occur syndromic, involving other abnormalities, or isolated. The term is from Greek trigonon, "triangle", and kephale, "head".

Trigonocephaly
Fused suture in trigonocephaly
SpecialtyMedical genetics

Cause

Trigonocephaly can either occur syndromatic or isolated. Trigonocephaly is associated with the following syndromes: Opitz syndrome, Muenke syndrome, Jacobsen syndrome, Baller-Gerold syndrome and Say-Meyer syndrome. The etiology of trigonocephaly is mostly unknown although there are three main theories.[1] Trigonocephaly is probably a multifactorial congenital condition, but due to limited proof of these theories this cannot safely be concluded.[2]

Intrinsic bone malformation

The first theory assumes that the origin of pathological synostosis lies within disturbed bone formation early on in the pregnancy. Causes can either be genetic[3][4][5][6] (9p22-24, 11q23, 22q11, FGFR1 mutation),[7] metabolic[8] (TSH suppletion in hypothyroidism)[9][10] or pharmaceutical[11] (valproate in epilepsy).[12][13]

Trigonocephaly as a kind of craniosynostosis

Fetal head constrain

The second theory says that synostosis begins when the fetal head gets hindered in the pelvic outlet during birth.[14][15]

Intrinsic brain malformation

The third theory predominates disturbed brain formation of the two frontal lobes as the main issue behind synostosis.[16][17][18] Limited growth of the frontal lobes leads to an absence of stimuli for cranial growth, therefore causing premature fusion of the metopic suture.

Diagnosis

Diagnosis can be characterized by typical facial and cranial deformities.[2][19]

Observatory signs of trigonocephaly are:

Imaging techniques (3D-CT, Röntgenography, MRI) show:

  • epicanthal folds in limited cases
  • teardrop-shaped orbits angulated towards the midline of the forehead ('surprised coon' sign) in severe cases
  • a contrast difference between a röntgenograph of a normal and a trigonocephalic skull
  • anterior curving of the metopic suture seen from lateral view of the cranium on a röntgenograph
  • a normal cephalic index (maximum cranium width / maximum cranium length) however, there is bitemporal shortening and biparietal broadening

The neuropsychological development is not always affected. These effects are only visible in a small percentage of children with trigonocephaly or other suture synostoses.

Neuropsychological signs are:

Treatment

Treatment is surgical with attention to form and volume. Surgery usually takes place before the age of one since it has been reported that the intellectual outcome is better.[27][28][20][21][22][29][30][31][32]

A. Fronto-supraorbital advancement and remodelling – before remodelling
B. Fronto-supraorbital advancement and remodelling – after remodelling

Fronto-supraorbital advancement and remodelling

A form of surgery is the so-called fronto-supraorbital advancement and remodelling.[33] Firstly, the supraorbital bar is remodelled by a wired greenstick fracture to straighten it. Secondly, the supraorbital bar is moved 2 cm. forward and fixed only to the frontal process of the zygoma without fixation to the cranium. Lastly, the frontal bone is divided into two, rotated and attached to the supraorbital bar causing a nude area (craniectomy) between the parietal bone and frontal bone. Bone will eventually regenerate since the dura mater lies underneath (the dura mater has osteogenic capabilities). This results in an advancement and straightening of the forehead.

'Floating forehead technique'

The so-called 'floating forehead technique'[2] combined with the remodelling of the supraorbital bar is derived from the fronto-supraorbital advancement and remodelling. The supraorbital bar is remodelled as described above.[34][35] The frontal bone is split in two pieces. Instead of using both pieces as in fronto-supraorbital advancement and remodelling, only one piece is rotated and attached to the supraorbital bar. This technique also leaves a craniectomy behind.[36]

Other

The simplest form of surgery for trigonocephaly was suturectomy.[37][21][34][38][39] However, as this technique was insufficient to correct the deformities, it is not used anymore.

Distraction osteogenesis is based on creating more cranial space for the brain by gradually moving the bones apart. This can be achieved by using springs.[40]

  • Minimal invasive endoscopic surgery[2]

These approaches are 2D solutions for a 3D problem, therefore the results are not optimal. Distraction osteogenesis and minimal invasive endoscopic surgery are yet in experimental phase.

Outcomes

Surgical

Trigonocephaly seems to be the most compliant form of craniosynostosis for surgery.[22] Because of standardization of current surgical approaches there is no surgical mortality and complications are few to none.[2][41][42] The simple suturectomy is presently insufficient to adjust the complicated growth restrictions caused by metopic synostosis.[2] On the other hand, the fronto-supraorbital advancement and remodelling and the 'floating forehead technique' create sufficient space for brain growth and result in a normal horizontal axis of the orbits and supraorbital bar. The fronto-supraorbital advancement and remodelling is the most used method nowadays.[41] Over the past few years distraction osteogenesis has been gradually acknowledged since it has a positive effect on hypotelorism. Expanding the distance between the orbits using springs seems to be successful.[2][43][44][45] However, there are discussions whether hypotelorism really needs to be corrected.[46] The minimal invasive endoscopic surgery has been gaining attention since the early '90s, however, it has technical limitations (only strip craniectomy is possible).[2] Attempts have been made to reach beyond these limits.[47][48][49][50][51]

Aesthetic

Aesthetic outcome of metopic synostosis surgery is persistently good with reoperation hazards below 20%.[52][53] In 1981 Anderson advised that craniofacial operations for synostosis should be as extensive as necessary after a study of 107 cases of metopic and coronal synostosis.[21] Surgery does not provide a 100% natural outcome, mostly there will be minor irregularities. Reoperations are usually performed on more severe cases (including syndromic metopic synostosis). The hypotelorism and temporal hollowing are the most difficult to correct: the hypotelorism usually remains under corrected and a second operation is often needed for correction of temporal hollowing.[52][54]

Neurological

The highest rate of neurological problems of single suture synostosis are seen in patients with trigonocephaly.[2] Surgery is performed generally before the age of one because of claims of better intellectual outcome.[27][28][20][21][22][29][30][31][32] Seemingly surgery does not influence the high incidence of neurodevelopment problems in patients with metopic synostosis. Neurological disorders such as ADHD, ASD, ODD and CD are seen in patients with trigonocephaly. These disorders are usually also associated with decreased IQ. The presence of ADHD, ASD and ODD is higher in cases with an IQ below 85. This is not the case with CD which showed an insignificant increase at an IQ below 85.[2]

Epidemiology

The incidence of metopic synostosis is roughly between 1:700 and 1:15.000 newborns globally (differs per country).[11][55] Trigonocephaly is seen more in males than females ranging from 2:1 to 6,5:1.[37][56][27][28] Hereditary relations in metopic synostosis have been found of which 5,5% were well defined syndromic.[11] Maternal age and a birth weight of less than 2500g may also play a role in trigonocephaly.[57] These data are based on estimations and do not give factual information.

Only one article gives valuable and reliable information regarding the incidence of metopic synostosis in the Netherlands. The incidence in the Netherlands showed an increase from 0.6 (1997) to 1.9 (2007) for every 10.000 live births.[58]

History

In former times people born with malformed skulls were rejected based upon their appearance.[1][59] This still persists today in various parts of the world even though the intellectual development is often normal.[2] The Austrian physician Franz Joseph Gall presented the science of phrenology in the early 19th century through his work The Anatomy and Physiology of the Nervous System in General, and of the Brain in Particular.[60]

Hippocrates described trigonocephaly as follows: Men's heads are by no means all like to one another, nor are the sutures of the head of all men constructed in the same form. Thus, whoever has a prominence in the anterior part of the head (by prominence is meant the round protuberant part of the bone which projects beyond the rest of it), in him the sutures of the head take the form of the Greek letter 'tau', τ.[61][62]

Hermann Welcker coined the term trigonocephaly in 1862. He described a child with a V-shaped skull and a cleft lip.[63]

Via a photo shown on a Facebook page, the mother of a child previously diagnosed with this condition recognised the symptoms and reported them to the family involved, resulting in an immediate diagnosis that medical professionals had overlooked in all earlier consultations.[64]

References

  1. Strickler M, van der Meulen J, Rahael B, Mazolla R. Craniofacial malformations. Edinburgh, London, Melbourne, New York: Churchill Livingston, 1990.
  2. Meulen, Jacobus Josephus Nicolaas Marie van der (2009). On trigonocephaly. Optima Grafische Communicatie. ISBN 978-90-8559-601-1.
  3. Wilkie, AO (1997). "Craniosynostosis: Genes and mechanisms". Human Molecular Genetics. 6 (10): 1647–56. doi:10.1093/hmg/6.10.1647. PMID 9300656.
  4. Wilkie, AO; Bochukova, EG; Hansen, RM; Taylor, IB; Rannan-Eliya, SV; Byren, JC; Wall, SA; Ramos, L; Venâncio, M; Hurst, Jane A.; O'Rourke, Anthony W.; Williams, Louise J.; Seller, Anneke; Lester, Tracy (2007). "Clinical dividends from the molecular genetic diagnosis of craniosynostosis". American Journal of Medical Genetics Part A. 143A (16): 1941–9. doi:10.1002/ajmg.a.31905. PMID 17621648.
  5. Frydman M, Kauschansky A, Elian E. Trigonocephaly; a new familiail syndrome. Am J Med Genet 1984: 18: 55-9.Frydman, M; Kauschansky, A; Elian, E; Opitz, John M. (1984). "Trigonocephaly: A new familial syndrome". American Journal of Medical Genetics. 18 (1): 55–9. doi:10.1002/ajmg.1320180109. PMID 6741996.
  6. Hennekam, RC; Van Den Boogaard, MJ (1990). "Autosomal dominant craniosynostosis of the sutura metopica". Clinical Genetics. 38 (5): 374–7. doi:10.1111/j.1399-0004.1990.tb03598.x. PMID 2282717.
  7. Kress, W; Petersen, B; Collmann, H; Grimm, T (2000). "An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly". Cytogenetics and Cell Genetics. 91 (1–4): 138–40. doi:10.1159/000056834. PMID 11173846.
  8. Penfold, JL; Simpson, DA (1975). "Premature craniosynostosis-a complication of thyroid replacement therapy". The Journal of Pediatrics. 86 (3): 360–3. doi:10.1016/S0022-3476(75)80963-2. PMID 1113223.
  9. Johnsonbaugh, RE; Bryan, RN; Hierlwimmer, R; Georges, LP (1978). "Premature craniosynostosis: A common complication of juvenile thyrotoxicosis". The Journal of Pediatrics. 93 (2): 188–91. doi:10.1016/S0022-3476(78)80493-4. PMID 209162.
  10. Rasmussen, SA; Yazdy, MM; Carmichael, SL; Jamieson, DJ; Canfield, MA; Honein, MA (2007). "Maternal thyroid disease as a risk factor for craniosynostosis". Obstetrics and Gynecology. 110 (2 Pt 1): 369–77. doi:10.1097/01.AOG.0000270157.88896.76. PMID 17666613.
  11. Lajeunie, E; Le Merrer, M; Marchac, D; Renier, D (1998). "Syndromal and nonsyndromal primary trigonocephaly: Analysis of a series of 237 patients". American Journal of Medical Genetics. 75 (2): 211–5. doi:10.1002/(SICI)1096-8628(19980113)75:2<211::AID-AJMG19>3.0.CO;2-S. PMID 9450889.
  12. Valentin, M; Ducarme, G; Yver, C; Vuillard, E; Belarbi, N; Renier, D; Luton, D (2008). "Trigonocephaly and valproate: A case report and review of literature". Prenatal Diagnosis. 28 (3): 259–61. doi:10.1002/pd.1948. PMID 18264949.
  13. Ardinger, HH; Atkin, JF; Blackston, RD; Elsas, LJ; Clarren, SK; Livingstone, S; Flannery, DB; Pellock, JM; Harrod, MJ; Lammer, Edward J.; Majewski, Frank; Schinzel, Albert; Toriello, Helga V.; Hanson, James W.; Optiz, John M.; Reynolds, James F. (1988). "Verification of the fetal valproate syndrome phenotype". American Journal of Medical Genetics. 29 (1): 171–85. doi:10.1002/ajmg.1320290123. PMID 3125743.
  14. Graham Jr, JM; Smith, DW (1980). "Metopic craniostenosis as a consequence of fetal head constraint: Two interesting experiments of nature". Pediatrics. 65 (5): 1000–2. PMID 7367110.
  15. Smartt Jr, JM; Karmacharya, J; Gannon, FH; Teixeira, C; Mansfield, K; Hunenko, O; Shapiro, IM; Kirschner, RE (2005). "Intrauterine fetal constraint induces chondrocyte apoptosis and premature ossification of the cranial base". Plastic and Reconstructive Surgery. 116 (5): 1363–9. doi:10.1097/01.prs.0000182224.98761.cf. PMID 16217480.
  16. Riemenschneider, PA (1957). "Trigonocephaly". Radiology. 68 (6): 863–5. doi:10.1148/68.6.863. PMID 13441914.
  17. Moss, ML (1959). "The pathogenesis of premature cranial synostosis in man". Acta Anatomica. 37 (4): 351–70. doi:10.1159/000141479. PMID 14424622.
  18. Kapp-Simon, KA; Speltz, ML; Cunningham, ML; Patel, PK; Tomita, T (2007). "Neurodevelopment of children with single suture craniosynostosis: A review". Child's Nervous System. 23 (3): 269–81. doi:10.1007/s00381-006-0251-z. PMID 17186250.
  19. Anderson, Frank M; Gwinn, John L; Todt, John C (Sep 19). "Trigonocephaly. Identity and surgical treatment". Journal of Neurosurgery. 19 (9): 723–30. doi:10.3171/jns.1962.19.9.0723. PMID 13861226. Check date values in: |date=, |year= / |date= mismatch (help)
  20. Shillito Jr, J; Matson, DD (1968). "Craniosynostosis: A review of 519 surgical patients". Pediatrics. 41 (4): 829–53. PMID 5643989.
  21. Anderson, FM (1981). "Treatment of coronal and metopic synostosis: 107 cases". Neurosurgery. 8 (2): 143–9. doi:10.1227/00006123-198102000-00001. PMID 7207779.
  22. Collmann, H; Sörensen, N; Krauss, J (1996). "Consensus: Trigonocephaly". Child's Nervous System. 12 (11): 664–8. doi:10.1007/BF00366148. PMID 9118128.
  23. Aryan, HE; Jandial, R; Ozgur, BM; Hughes, SA; Meltzer, HS; Park, MS; Levy, ML (2005). "Surgical correction of metopic synostosis". Child's Nervous System. 21 (5): 392–8. doi:10.1007/s00381-004-1108-y. PMID 15714353.
  24. Oi, S; Matsumoto, S (1987). "Trigonocephaly (metopic synostosis). Clinical, surgical and anatomical concepts". Child's Nervous System. 3 (5): 259–65. doi:10.1007/BF00271819. PMID 3427566.
  25. Sidoti Jr, EJ; Marsh, JL; Marty-Grames, L; Noetzel, MJ (1996). "Long-term studies of metopic synostosis: Frequency of cognitive impairment and behavioral disturbances". Plastic and Reconstructive Surgery. 97 (2): 276–81. doi:10.1097/00006534-199602000-00002. PMID 8559809.
  26. Kapp-Simon, KA (1998). "Mental development and learning disorders in children with single suture craniosynostosis". The Cleft Palate-Craniofacial Journal. 35 (3): 197–203. doi:10.1597/1545-1569(1998)035<0197:MDALDI>2.3.CO;2. PMID 9603552.
  27. Dirocco, C; Caldarelli, M; Ceddia, A; Iannelli, A; Velardi, F (1989). "Craniostenosis. Analysis of 161 cases surgically treated during the first year of life". Minerva Pediatrica. 41 (8): 393–404. PMID 2601658.
  28. Dhellemmes, P; Pellerin, P; Lejeune, JP; Lepoutre, F (1986). "Surgical treatment of trigonocephaly. Experience with 30 cases". Child's Nervous System. 2 (5): 228–32. doi:10.1007/BF00272491 (inactive 2019-08-20). PMID 3791279.
  29. Marchac, D; Renier, D; Broumand, S (1994). "Timing of treatment for craniosynostosis and facio-craniosynostosis: A 20-year experience". British Journal of Plastic Surgery. 47 (4): 211–22. doi:10.1016/0007-1226(94)90001-9. PMID 8081607.
  30. McCarthy, JG; Epstein, F; Sadove, M; Grayson, B; Zide, B; McCarthy, Joseph G. (1984). "Early surgery for craniofacial synostosis: An 8-year experience". Plastic and Reconstructive Surgery. 73 (4): 521–33. doi:10.1097/00006534-198404000-00001. PMID 6709733.
  31. Renier, D; Lajeunie, E; Arnaud, E; Marchac, D (2000). "Management of craniosynostoses". Child's Nervous System. 16 (10–11): 645–58. doi:10.1007/s003810000320. PMID 11151714.
  32. Whitaker, LA; Bartlett, SP; Schut, L; Bruce, D (1987). "Craniosynostosis: An analysis of the timing, treatment, and complications in 164 consecutive patients". Plastic and Reconstructive Surgery. 80 (2): 195–212. doi:10.1097/00006534-198708000-00006. PMID 3602170.
  33. Van Der Meulen, JJ; Nazir, PR; Mathijssen, IM; Van Adrichem, LN; Ongkosuwito, E; Stolk-Liefferink, SA; Vaandrager, MJ (2008). "Bitemporal depressions after cranioplasty for trigonocephaly: A long-term evaluation of (supra) orbital growth in 92 patients". The Journal of Craniofacial Surgery. 19 (1): 72–9. doi:10.1097/scs.0b013e31815c8a68. PMID 18216668.
  34. Marchac, D (June 1978). "Radical forehead remodeling for craniostenosis". Plastic and Reconstructive Surgery. 61 (6): 823–35. doi:10.1097/00006534-197861060-00001. PMID 662945.
  35. Meling, TR; Due-Tønnessen, BJ; Helseth, E (2000). "Metotopic craniosynostoses". Tidsskrift for den Norske Laegeforening : Tidsskrift for Praktisk Medicin, NY Raekke. 120 (26): 3147–50. PMID 11109361.
  36. Marchac, D; Renier, D; Jones, BM (1988). "Experience with the "floating forehead"". British Journal of Plastic Surgery. 41 (1): 1–15. doi:10.1016/0007-1226(88)90137-3. PMID 3345401.
  37. Friede, H; Alberius, P; Lilja, J; Lauritzen, C (1990). "Trigonocephaly: Clinical and cephalometric assessment of craniofacial morphology in operated and nontreated patients". The Cleft Palate Journal. 27 (4): 362–7, discussion 368. doi:10.1597/1545-1569(1990)027<0362:TCACAO>2.3.CO;2. PMID 2253382.
  38. Hoffman, HJ; Mohr, G (1976). "Lateral canthal advancement of the supraorbital margin. A new corrective technique in the treatment of coronal synostosis". Journal of Neurosurgery. 45 (4): 376–81. doi:10.3171/jns.1976.45.4.0376. PMID 956873.
  39. Delashaw, JB; Persing, JA; Park, TS; Jane, JA (1986). "Surgical approaches for the correction of metopic synostosis". Neurosurgery. 19 (2): 228–34. doi:10.1227/00006123-198608000-00008. PMID 3748350.
  40. Akai, Takuya; Iizuka, Hideaki; Kawakami, Shigehiko (2006). "Treatment of craniosynostosis by distraction osteogenesis". Pediatric Neurosurgery. 42 (5): 288–92. doi:10.1159/000094064. PMID 16902340.
  41. Di Rocco, C; Velardi, F; Ferrario, A; Marchese, E (1996). "Metopic synostosis: In favour of a "simplified" surgical treatment". Child's Nervous System. 12 (11): 654–63. doi:10.1007/BF00366147. PMID 9118127.
  42. Galassi E, Giulioni M, Acciarri N, Cavina C, Pistorale T. Marchac procedure in the early treatment of metopic and coronal synostoses. Presented at the Consensus Conference on Craniosynostoses, Rome 1995.
  43. Lauritzen, CG; Davis, C; Ivarsson, A; Sanger, C; Hewitt, TD (2008). "The evolving role of springs in craniofacial surgery: The first 100 clinical cases". Plastic and Reconstructive Surgery. 121 (2): 545–54. doi:10.1097/01.prs.0000297638.76602.de. PMID 18300975.
  44. Maltese, G; Tarnow, P; Lauritzen, CG (2007). "Spring-assisted correction of hypotelorism in metopic synostosis". Plastic and Reconstructive Surgery. 119 (3): 977–84. doi:10.1097/01.prs.0000252276.46113.ee. PMID 17312504.
  45. Davis, C; Lauritzen, CG (2009). "Frontobasal suture distraction corrects hypotelorism in metopic synostosis". The Journal of Craniofacial Surgery. 20 (1): 121–4. doi:10.1097/SCS.0b013e318190e25d. PMID 19165007.
  46. Fearon, JA; Kolar, JC; Munro, IR (1996). "Trigonocephaly-associated hypotelorism: Is treatment necessary?". Plastic and Reconstructive Surgery. 97 (3): 503–9, discussion 510–11. doi:10.1097/00006534-199603000-00001. PMID 8596780.
  47. Barone, CM; Jimenez, DF (1999). "Endoscopic craniectomy for early correction of craniosynostosis". Plastic and Reconstructive Surgery. 104 (7): 1965–73, discussion 1974–5. doi:10.1097/00006534-199912000-00003. PMID 11149758.
  48. Hinojosa, J; Esparza, J; García-Recuero, I; Romance, A (2007). "Endoscopically assisted fronto-orbitary correction in trigonocephaly". Cirugia Pediatrica : Organo Oficial de la Sociedad Espanola de Cirugia Pediatrica. 20 (1): 33–8. PMID 17489491.
  49. Murad, GJ; Clayman, M; Seagle, MB; White, S; Perkins, LA; Pincus, DW (2005). "Endoscopic-assisted repair of craniosynostosis". Neurosurgical Focus. 19 (6): E6. doi:10.3171/foc.2005.19.6.7. PMID 16398483.
  50. Jimenez, DF; Barone, CM (1998). "Endoscopic craniectomy for early surgical correction of sagittal craniosynostosis". Journal of Neurosurgery. 88 (1): 77–81. doi:10.3171/jns.1998.88.1.0077. PMID 9420076.
  51. Hinojosa, J; Esparza, J; Muñoz, MJ (2007). "Endoscopic-assisted osteotomies for the treatment of craniosynostosis". Child's Nervous System. 23 (12): 1421–30. doi:10.1007/s00381-007-0473-8. PMID 17899127.
  52. Greenberg, BM; Schneider, SJ (2006). "Trigonocephaly: Surgical considerations and long term evaluation". The Journal of Craniofacial Surgery. 17 (3): 528–35. doi:10.1097/00001665-200605000-00024. PMID 16770193.
  53. Cohen, SR; Maher, H; Wagner, JD; Dauser, RC; Newman, MH; Muraszko, KM (1994). "Metopic synostosis: Evaluation of aesthetic results". Plastic Surgery. 94 (6): 759–67. doi:10.1097/00006534-199411000-00002. PMID 7972420.
  54. Posnick, JC; Lin, KY; Chen, P; Armstrong, D (1994). "Metopic synostosis: Quantitative assessment of presenting deformity and surgical results based on CT scans". Plastic and Reconstructive Surgery. 93 (1): 16–24. doi:10.1097/00006534-199401000-00003. PMID 8278471.
  55. Alderman, BW; Fernbach, SK; Greene, C; Mangione, EJ; Ferguson, SW (1997). "Diagnostic practice and the estimated prevalence of craniosynostosis in Colorado". Archives of Pediatrics & Adolescent Medicine. 151 (2): 159–64. doi:10.1001/archpedi.1997.02170390049009. PMID 9041871.
  56. Genitori, L; Cavalheiro, S; Lena, G; Dollo, C; Choux, M (1991). "Skull base in trigonocephaly". Pediatric Neurosurgery. 17 (4): 175–81. doi:10.1159/000120591. PMID 1822130.
  57. Boulet, SL; Rasmussen, SA; Honein, MA (2008). "A population-based study of craniosynostosis in metropolitan Atlanta, 1989-2003". American Journal of Medical Genetics Part A. 146A (8): 984–91. doi:10.1002/ajmg.a.32208. PMID 18344207.
  58. Kweldam, CF; Van Der Vlugt, JJ; Van Der Meulen, JJ (2010). "The incidence of craniosynostosis in the Netherlands, 1997-2007". Journal of Plastic, Reconstructive & Aesthetic Surgery. 64 (5): 583–588. doi:10.1016/j.bjps.2010.08.026. PMID 20888312.
  59. Vermeij-Keers, C; Mazzola, RF; Van Der Meulen, JC; Strickler, M (1983). "Cerebro-craniofacial and craniofacial malformations: An embryological analysis". The Cleft Palate Journal. 20 (2): 128–45. PMID 6406099.
  60. Phrenology. http://www.phrenology.org/
  61. Hippocrates. On injuries of the head. Med classics 1938: 3: 145-60.
  62. Dimopoulos, VG; Machinis, TG; Fountas, KN; Robinson, JS (2005). "Head injury management algorithm as described in Hippocrates' "peri ton en cephali traumaton"". Neurosurgery. 57 (6): 1303–5, discussion 1303–5. doi:10.1227/01.NEU.0000187321.13149.B9. PMID 16331180.
  63. Welcker H. Untersugungen uber wachtsum und bau des menschlischen Schädels. Leipzig: Engelmann, 1862.
  64. "British mum learns baby son has rare condition thanks to stranger on Facebook". News.com.au. 9 May 2012. Retrieved 31 May 2012.
Classification
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.