Head Development - Abnormalities

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Fetal Alcohol Syndrome facial features

Many head and neck structures are derived from pharyngeal arches 1 and 2 which undergo extensive remodelling during head development. Within the head are embedded many other complex developing structures, it is therefore not uncommon for this body region to have many associated abnormalities. Note that for neural and other head organs, look at the relevant section of notes which have their own abnormalities page.

Head Links: Introduction | Medicine Lecture | Medicine Lab | Science Lecture | Lecture Movie | Science Lab | pharyngeal arch | Craniofacial Seminar | Mouth | palate | Tongue | placode | skull | neural crest | Head and Face Movies | Abnormalities | Category:Head
Historic Head Embryology  
1910 Skull | 1910 Skull Images | 1912 Nasolacrimal Duct | 1921 Human Brain Vascular | 1923 Head Subcutaneous Plexus | 1919 21mm Embryo Skull | 1920 Human Embryo Head Size | 1921 43 mm Fetal Skull | Historic Disclaimer
Palate Links: palate | cleft lip and palate | cleft palate | Head Development | Category:Palate

Abnormality Links: Introduction | Genetic | Environmental | Unknown | Teratogens | Ectopic Implantation | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Integumentary | Musculoskeletal | Limb | Neural | Neural Crest | Renal | Respiratory | Placenta | Sensory | Hearing | Vision | Twinning | Developmental Origins of Health and Disease | ICD-10
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

  • Treacher Collins syndrome: a clinical and molecular study based on a large series of patients[1] Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. METHODS: We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. ...CONCLUSION: Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect."

Head and Neck Abnormalities

  • Congenital Auricular Sinuses and Cysts
  • Pharyngeal Abnormalities - Sinuses, Fistula, Cysts, Vestiges
  • Pyriform Sinus Fistula (Piriform Sinus Fistula)
  • First Arch Syndrome
  • Treacher Collins syndrome
  • Pierre Robin syndrome
  • DiGeorge syndrome
  • Accessory thymic tissue
  • Ectopic parathyroid glands
  • Thyroid Gland Anomalies

Pharyngeal Abnormalities

There are typically four different terms for the different types of pharyngeal abnormalities, all of these are relatively rare.


A pharyngeal groove defect, when a portion of the groove persists and opens to the skin surface, located laterally on the neck.


A pharyngeal membrane defect, a tract extends from pharynx (tonsillar fossa) beween the carotid arteries (internal and external) to open on side of neck.


A cervical sinus defect, remants of the cervical sinus remains as a fluid-filled cyst lined by an epithelium.


Cartilaginous or bony developmental remnants that lie under the skin on side of neck.


The way in which the upper jaw forms from fusion of the smaller upper prominence of the first pharyngeal arch leads to a common congenital defect in this region called "clefting", which may involve either the upper lip, the palate or both structures.

Cleft Lip

Bilateral cleft palate
  • International Classification of Diseases code 749.1 for isolated cleft lip and 749.2 for cleft lip with cleft palate.
  • Australian national rate (1982-1992) 8.1 - 9.9 /10,000 births.
  • Of 2,465 infants 6.2% were stillborn and 7.8% liveborn died during neonatal period.
  • rate similar in singleton and twin births.

Links: Cleft Lip and Palate

Cleft Palate

Cleft palate
  • International Classification of Diseases code 749.0
  • Australian national rate (1982-1992) 4.8 - 6 /10,000 births.
  • Of 1,530 infants 5.5% were stillborn and 11.5% liveborn died during neonatal period.
  • slightly more common in twin births than singleton.

(Data: Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352)

Links: Cleft Palate | Development Animation - Palate 1 | Development Animation - Palate 2 | Orofacial Cleft with or without cleft palate

Search Pubmed Now: cleft lip | cleft palate

First Arch Syndrome

There are 2 major types of genetic first arch syndromes, Treacher Collins and Pierre Robin, both result in extensive facial abnormalites.

Search Pubmed Now: facial cleft

Treacher Collins syndrome (TCS)

Treacher Collins Syndrome (head lateral view)
  • a rare autosomal dominant craniofacial disorder (1:50,000)
  • TCOF1 gene encoding Treacle protein
    • caused by frameshift deletions or duplications
    • located chromosome 5
    • encodes a serine/alanine-rich nucleolar phospho-protein


  • hypoplasia of the mandible and zygomatic complex
  • down-slanting palpebral fissures
  • coloboma of the lower eyelid
  • absence of eyelashes medial to the defect
  • external and middle ear malformation
  • conductive hearing loss

Zebrafish Model

Fishing the molecular bases of Treacher Collins syndrome[2]

"Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development."

Links: OMIM - Treacher Collins Syndrome | Medline Plus - Treacher Collins Syndrome | PMID 20301704

Pierre Robin syndrome

Newborn micrognathia[3]

Also called Pierre Robin sequence.

  • micrognathia
  • retroglossia
  • U-shaped posterior cleft palate

Pierre Robin sequence 01.jpg

Frontal and lateral views of an infant with Pierre Robin sequence.[4]

Links: OMIM - Pierre Robin Syndrome | Medline Plus - Pierre Robin Syndrome | Pierre Robin Network


Refers to the congenital absence or partial absence of the lower jaw and can also be associated with holoprosencephaly (agnathia-holoprosencephaly).


Historic drawings 1865, 1909.

Mandibular Hypoplasia

Adult mandible

One of the most common malformations of the facial skeleton usually associated with a deficient gonial angle, ascending ramus, and mandibular corpus.

  • gonial angle - (angle of the jaw, angle of the mandible) the angle formed by the junction of the posterior and lower borders of the human lower jaw.
  • ascending ramus - the more or less vertical part of the jaw which carries the joint with the skull.
  • mandibular corpus - the horizontal or tooth-bearing portion of the mandible.

Links: Growth of the Mandible

Choanal Atresia

Choanal atresia computed tomography[5]
  • Choanal atresia is the most common form of congenital nasal obstruction, usually diagnosed at birth.[5]
  • failure of the posterior nasal cavity (choanae) to communicate with the nasopharynx.
  • Thought to be secondary to an abnormality during the rupture of the buccopharyngeal membrane in the embryological period.

Links: Smell Development

Cephalic Disorders

Cephalic (Greek, kephale = head) are a group of abnormalities that relate to a wide range of skeletal (skull) and neural (brain) associated defects.

Neural Associated

Anencephaly, Hydrocephalus, Encephalocele, Colpocephaly (occipital horn enlargement), Lissencephaly (smooth brain), Porencephaly (cyst or cavity in cerebral hemisphere), Acephaly (absence of head), Exencephaly (brain outside skull), Macrocephaly (large head), Micrencephaly (small brain),

Skeletal Associated

  • Otocephaly - absence of lower jaw.
  • Brachycephaly - premature fusion of coronal suture.
  • Oxycephaly - premature fusion of coronal suture + other.
  • Plagiocephaly - premature unilateral fusion of coronal or lambdoid sutures.
  • Scaphocephaly - premature fusion of sagittal suture.
  • Trigonocephaly - premature fusion of the metopic suture.

Links: Skull Development

Fetal Alcohol Syndrome

Fetal Alcohol Syndrome facial features

(FAS) Due to alcohol in early development (week 3+) leading to both facial and neurological abnormalities. This disorder was clinically described (USA) in humans about 30 years ago (1973), while historically alcohol's teratogenic effects were identified in the early 20th century in a mix with the prohibition cause of the period. Similar effects without the obvious alterations to appearance, but with nervous system effects, are sometimes identified as Fetal Alcohol Effects (FAE). Alcohol is able to cross the placenta from maternal circulation through the placenta into fetal circulation.

FAS Features:

  • lowered ears, small face, mild+ retardation
  • Microcephaly - leads to small head circumference
  • Short Palpebral fissure - opening of eye
  • Epicanthal folds - fold of skin at inside of corner of eye
  • Flat midface
  • Low nasal bridge
  • Indistinct Philtrum - vertical grooves between nose and mouth
  • Thin upper lip
  • Micrognathia - small jaw

Exposure of embryos in vitro to ethanol simulates premature differentiation of prechondrogenic mesenchyme of the facial primordia (1999)

Links: Abnormal Development - Fetal Alcohol Syndrome

Congenital Nasolacrimal Duct Obstruction

The nasolacrimal groove appears in week 4 to 5 forming a cord of ectoderm epithelium extending from the eyelids to the nose. The cord canalises from the third month beginning at the eyelid punctum and extends toward the nose. Canalization is usually complete by birth. If not completed by birth it can cause persistent tearing and ocular discharge in infants and young children. The condition is called Congenital Nasolacrimal Duct Obstruction (CNDO) and generally resolve spontaneously.


  1. Vincent M, Geneviève D, Ostertag A, Marlin S, Lacombe D, Martin-Coignard D, Coubes C, David A, Lyonnet S, Vilain C, Dieux-Coeslier A, Manouvrier S, Isidor B, Jacquemont ML, Julia S, Layet V, Naudion S, Odent S, Pasquier L, Pelras S, Philip N, Pierquin G, Prieur F, Aboussair N, Attie-Bitach T, Baujat G, Blanchet P, Blanchet C, Dollfus H, Doray B, Schaefer E, Edery P, Giuliano F, Goldenberg A, Goizet C, Guichet A, Herlin C, Lambert L, Leheup B, Martinovic J, Mercier S, Mignot C, Moutard ML, Perez MJ, Pinson L, Puechberty J, Willems M, Randrianaivo H, Szakszon K, Szaskon K, Toutain A, Verloes A, Vigneron J, Sanchez E, Sarda P, Laplanche JL & Collet C. (2016). Treacher Collins syndrome: a clinical and molecular study based on a large series of patients. Genet. Med. , 18, 49-56. PMID: 25790162 DOI.
  2. Weiner AM, Scampoli NL & Calcaterra NB. (2012). Fishing the molecular bases of Treacher Collins syndrome. PLoS ONE , 7, e29574. PMID: 22295061 DOI.
  3. Morokuma S, Anami A, Tsukimori K, Fukushima K & Wake N. (2010). Abnormal fetal movements, micrognathia and pulmonary hypoplasia: a case report. Abnormal fetal movements. BMC Pregnancy Childbirth , 10, 46. PMID: 20716376 DOI.
  4. Sesenna E, Magri AS, Magnani C, Brevi BC & Anghinoni ML. (2012). Mandibular distraction in neonates: indications, technique, results. Ital J Pediatr , 38, 7. PMID: 22300418 DOI.
  5. 5.0 5.1 Al-Noury K & Lotfy A. (2011). Role of multislice computed tomography and local contrast in the diagnosis and characterization of choanal atresia. Int J Pediatr , 2011, 280763. PMID: 21772853 DOI.



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Cite this page: Hill, M.A. (2018, April 25) Embryology Head Development - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Head_Development_-_Abnormalities

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G