Genetic Counseling And Craniofacial Disorders


Genetic disorder indicates a disease related to DNA (hereditary materials) which could be due to changes in the genetic materials, gene mutations or altered gene expressions (genetic disorders) and causing birth defects (2% to 3%). Birth defects may or may not be visibly marked/identified or expressed immediately during/after birth; sometimes may take few months to years so it is always tricky to figure out the exact cause of birth defects though genetic or hereditary (~20%) and environment factors playing an important role. In 2008, World Health Organisation (WHO) indicated non-communicable diseases including birth defects (cleft lip and palate) are caused significant infant mortality and childhood morbidity in their ‘Global Burden of Disease’ (GBD) database.This has helped India to register and maintain the birth defects data and follow the international guidelines to prevent this non-syndromic disorders as India has high incidences (one in 700) as compared to the western countries (1 in 1,000), due to the large population size.

Figure 1 : Genetic counselling applications

Historical background of genetic counseling

William Bateson (1861-1926); an English biologist, used the term ‘genetics’ first time to describe the inheritance and the science of variation, later the term “genetics” used publicly at the “Third International Conference” on Plant Hybridization in London in 1906. (Ref 1, 2). In his 1994 book “Materials for the Study of Variation” the elaborated description on the existence of biological variation both continuously and discontinuously manner was mentioned. In 1940s the first genetic counseling clinics were established in the United States and the United Kingdom and the term ‘genetic counseling’ used in 1947 by Sheldon Clark Reed (Ref 3) along with genetic diseases like Huntington disease, mental retardation and cleft palates were described. Later in 1955 he published the book ‘Counseling in Medical Genetics’ and mentioned the importance of the counseling approach. Alan Frank Guttmacher, an American gynecologist realised the benefits of prenatal diagnosis and birth defects and was evaluated during 1970s, Later in 2003 the importance of the master’s-level-trained genetic counsellor was acknowledged. (Ref 4) Today a genetic counsellor role has become an integral part in oncological area. Corporates and many industries are recruiting genetic counselors to promote the genetic screening and educate our population to avail the facilities for a better future and guiding and supporting with the information to an individual, families affected by or at the risk of a genetic disorder. (Ref 5)

Figure 2: Genetic Disorders [Ref:]

Craniofacial Disorder

Congenital anomalies (CA) causing infant and childhood morbidity (2-3%) and approximately 1% have syndromes or multiple anomalies. Craniofacial anomalies (CFA) means the skull (cranium) bone and face (facial bones) related congenital problem and can range from mild to severe and most of the cases require surgery. Anomalies means ‘irregularity’. Cleft lip and palate (separation in the lip and the palate) is one of the very common type of craniofacial defects. (Ref 6) 30% of cleft cases are syndromic and rest are non-syndromic (~70%). Affected person facing social stigma which lowers their self-esteem. Speech and hearing defects are very common with complicated CFA which further compress the brain (low intelligence level) and the eye ball (partial to complete blindness). (Ref 7) A genetic counselor will guide with the appropriate genetic testing to confirm/identify the condition as CFA leads the risk for congenital heart defect.

Figure 3 : Craniofacial Disorders : Types and factors involvement. [Ref :]

All type of facial differences does not always due to genetic factors but it is always advisable that a child with facial differences should go for a genetics evaluation to clear the root cause issue. Antenatal ultrasonography (between 18 and 22 weeks gestation) is widely used in pregnancy to assess fetal growth and anatomy including craniofacial abnormalities to minimise birth defect probability. (Ref 8) A 3D fetal ultrasound can detect facial abnormalities or neural tube defects.

Orofacial clefts [cleft lip (CL) & cleft palate (CP)] : The affected individuals having issues with feeding, speech, hearing and dental problems, increased incidence of mental issues and mortality rates (Ref 9) along with higher risk of various types of cancer (breast, brain, and colon). (Ref 10, 11).

Chromosome involvement :

·The long arm of chromosome 8.

·del 22q11.2

· Trisomies 13 and 18, and del 4p

Inheritance involvement :

·Cleft palate with X linked inheritance (CPX)

Mutation involvement :

·PVRL1 (cell adhesion molecule), MSX1, IRF6, and TBX22 (transcription factors)

Craniosynostosis : Premature fusion of a single cranial suture (mostly), but if fusion of multiple sutures is involve then mostly linked to the genetic syndromes (syndromic craniosynostosis). (Ref 13).

Chromosome involvement :

·Deletion in the short arm of chromosome 7.

.Inheritance involvement :

·Autosomal dominant inheritance.

Mutation involvement :

·TWIST1 gene (heterozygous missense mutations)

Hemifacial Microsomia : Underdevelopment of one side of the jaw, which leads dental, feeding and speech problems. Breathing issues in severe cases. The disorder occurs about 50% more often in males than in females. (Ref 14).

Chromosome involvement :

·14q22.3 duplication

.Inheritance involvement :

·Mostly not inherited.

·Autosomal Dominance pattern (1 – 2%)

Mutation involvement :

ITPR1 mutation

Vascular Malformation : Abnormal growth & development of a vessel or a combination of vessels. It can be less severe, mild to extreme severe depends on the of the vessels involvement though this disorder is very rare (>1%). (Ref 15).

Chromosome involvement :

· Chromosome 9p21

.Inheritance involvement :

·Sporadic (TIE2 somatic mutations 50% cases)


·Autosomal dominant (mutation related)

Mutation involvement :

TIE2 (TEK) mutation

Hemangioma : A type of noncancerous growth in the blood vessels usually grow over a period of time and mostly subside without treatment. Other than skin & liver the tumor can grow in lung kidney, colon and brain. (Ref 16). Though incidences are lower for Asian & African population.

Chromosome involvement :

· Chromosome 5q

.Inheritance involvement :

·Autosomal dominant

Mutation involvement :

·Missense mutation in VEGFR3

Importance of Genetic counseling :

Genetic disorders which is affecting a child’s head/skull or facial appearance impacting very badly not only to the child but also to the parents. Guidelines of genetic testing will be provided by a genetic counsellor and the reports outcome will be interpreted to conclude on further course of action. If surgery is must then medical team will be there to guide but nonsurgical therapy like speech hearing issue, dental or psychological support etc will be guided by a genetic counselor.

Figure 4: Craniofacial Disorders – Panel of genetic tests (


1. Bateson W. (1906) The progress of genetic reseach; Report of the Third International Conference on Genetics. England: Royal Horticultural Society. pp. 90–97.

2. G.M. Shepherd (2010). Creating modern neuroscience, p. 17.

3. Anderson V. Elving (2003) Genetic Counseling Behavioural Genetics. AmericanJournal of Human Genetics. 73(1): 1 – 4.

4. John H. Marks (2004) The Importance of Genetic Counseling Am J Hum Genet. 74(3): 395–396. PMID: 15053013.

5. District of Columbia Department of Health (2010). Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; Chapter 4, Genetic Counseling.

6. Amanda J. Yoon, Binh N. Pham and Katrina M. Dipple (2016). Genetic Screening in Patients with Craniofacial Malformations. J Pediatr Genet. 5(4):220-224. doi: 10.1055/s-0036-1592423.

7. Express Healthcare (2013), The number of craniofacial anomalies including cleft lip and palate is a little higher in India.

8. Doaa Jabaz and Mohammed Abed (2021) Sonography 2nd Trimester Assessment, Protocols, And Interpretation. Stat Pearls Publishing LLC.

9. Wehby GL, Cassell CH (2010) The impact of orofacial clefts on quality of life and healthcare use and costs. Oral Dis. 16(1):3-10. [PubMed] [Ref list].

10. Risk of breast cancer in families with cleft lip and palate (2012). Dietz A, Pedersen DA, Jacobsen R, Wehby GL, Murray JC, Christensen K Ann Epidemiol. 22(1):37-42.

11. Zhu JL, Basso O, Hasle H, Winther JF, Olsen JH, Olsen (2002) Do parents of children with congenital malformations have a higher cancer risk? A nationwide study in Denmark. J Br J Cancer. 87(5):524-8.

12. Elizabeth J. Leslie and Mary L. Marazita. (2013) Genetics of Cleft Lip and Cleft Palate. Am J Med Genet C Semin Med Genet. 163(4): 246–258. doi:10.1002/ajmg.c.31381.

13. Mayo clinic, 1998-2021 Mayo Foundation for Medical Education and Research (MFMER). All rights reserved.

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14. MedlinePlus (2020)

15. Pascal Brouillard, Mikka Vikkula. (2007) Genetic causes of vascular malformations. Human Molecular Genetics, 16, Issue R2, Pages R140–R149.

16. Eileen Boye and Bjorn R. Olsen (2009) Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA Curr Opin Hematol. 16(3): 202–208.

doi:10.1097/MOH.0b013e32832a07ff. of Form

By – Dr. Rochana Ray



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