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Consanguinity and Eye

by | Jan 1, 2023 | Manuscripts | 0 comments

G. Sruthi, B. Optom

Fellowship in Clinical Optometry, Aravind Eye Care System, Chennai, India

 

Consanguinity is a mixture of two words taken from the Latin language; “con”  means similar, and “sanguineous”  means blood.  In clinical genetics, a consanguineous marriage is defined as a union between two individuals who are related as second cousins or closer in which the offspring of a consanguineous union is expected to inherit identical gene copies from both parents. Children born out of consanguineous unions may be at increased risk of acquiring genetic disorders because of the expression of autosomal recessive gene mutations inherited from a common ancestor in a homozygous state. The incidence of congenital malformations involving major systems of the body has been reported to be higher in consanguineous marriages, especially uncle-niece marriages compared to those between first cousins.

Grades of Consanguinity marriage

Figure 1: Grades of consanguinity marriage
(Image courtesy – https://sociovillage.wordpress.com/2016/09/28/consanguinity/)

The risk of severe birth defects varies, depending on both the kind of society in which the relationship exists, and the way studies measure a child’s health during the first few years of its life. The closer the biological relationship, the higher the chances for genetic disorders. First-degree relatives who are in a relationship have about a 30 percent risk of bearing a child with severe birth defects. The risk is about 2-3 percent in the third degree.

The most common causes of Consanguinity marriage are congenital anomalies, hearing and vision impairment, mental retardation or learning disability, Developmental delay, or failure to thrive inherited blood disorder, and unexplained neonatal or infant death in offspring. (1-3)

Table 1: Common ocular hereditary disorders with their common gene involved.

Diseases Description of the condition Common Gene Involved
Anterior segment
Congenital hereditary endothelial dystrophy (4)
  • It is a bilateral corneal condition characterised by cloudy cornea
  • It may be present from birth or may be infantile in onset
  • SLC4A11
Coloboma (5)
  • Coloboma of the iris, ciliary body, choroid, retina and/or optic nerve derive from failed or incomplete closure of the embryonic fissure during development
 27 Genes involved in this condition

  • PAX6
  • SHH
  • GDF3
  • RBP
Xeroderma pigmentosum (6)
  • It is characterised by extreme ultraviolet light (UV) sensitivity with the development of skin cancer very early in life
  • Mutation in at least 8 different genes cause XP
Oculocutaneous Albinism (7)
  • It is a group of rare inherited disorders characterised by a reduction or complete lack of melanin pigment in the skin, hair, and eyes
 It is caused by a mutation in many genes.

  • TYR
  • OCA2(P-gene)
  • TYRP1
  • SLC45A2
Nystagmus (8)
  • It is involuntary movements of the eye due to the areas of the brain that control eye movements that don’t work properly.
  • FRMD7
  • GPR143
Axenfeld Rieger Syndrome (9)
  • It is characterised by developmental abnormalities in the anterior chamber angle, iris, and trabecular meshwork and systemic abnormalities
  • FOXC1
  • FOXC2
  • PITX2
Congenital Glaucoma (10-11)
  • The presence of Haab striae suggests congenital glaucoma, and if seen without ocular developmental anomalies or systemic syndromes
  • CYP1B1
Congenital / Developmental Cataract (12)
  • It is an opacification of lens present at birth or developed after a few years of age.
 More than 100 genes responsible for cataract and associated conditions
Posterior segment
Leber Congenital Amaurosis (13)
  • It is the most severe retinal dystrophy causing blindness by the age of 1 year in most cases.
 Frequently mutated genesis in LCA

  • CEP290
  • GUCY2D
  • CRB1
  • RPE65
Retinitis pigmentosa (14)
  • Patients with RP characteristically develop night blindness and difficulty with the mid-peripheral visual field in adolescence due to progressive dysfunction of predominantly rod photoreceptors with subsequent degeneration of cone photoreceptors and the retinal pigment epithelium (RPE).
 Frequently mutated genesis in LCA

  • RPGR
  • RP2
  • OFD1
Cone-rod dystrophy (15)
  • CRDs are inherited retinal dystrophies that belong to the pigmentary retinopathies group.
  • ABCA4
  • CRX
  • GUCY2D
  • RPGR
Stargardt’s Diseases
  • It is a rare genetic eye disease that happens when fatty material builds up on the macula
  • ABCA4
Familial exudative Vitreo-Retinopathy (16)
  • It is characterised by incomplete vascularization of the peripheral retina with subsequent retinal ischemia.
  • FZD4
  • LRP5
  • NDP
  • TSPAN12
Familial exudative Vitreo-Retinopathy (16)
  • It is characterised by incomplete vascularization of the peripheral retina with subsequent retinal ischemia.
  • FZD4
  • LRP5
  • NDP
  • TSPAN12
Vitelliform Dystrophy (17)
  • It is a genetic form of macular degeneration which causes progressive vision loss.
  • BEST1
  • PRPH2
  • VMD2
  • TU15B
Optic Atrophy (18)
  • It is characterised by the death of the retinal ganglion cell axons caused by different pathologies.
  • OPA1

Due to the sharing of genetic material from the common ancestor, the marriages between uncle, niece and first cousins result in genetic disorders in the offspring.

Table 2: How consanguinity results in hereditary diseases (19)

Relationship Average percentage of DNA shared
Parents to children 50
Brothers and sisters 50
Uncle and niece 25
First cousins 12.5

Genetic counselling and its importance

Genetic counselling is counselling a patient regarding genetics, risk factors and diseases caused by consanguinity. (20) It involves obtaining the family and medical history from the patient and referring the clinician and reviewing the medical records of the patient and family members. There are separate centres available for genetic counselling on consanguinity. Genetic counselling is critical and must be performed in a sensitive, caring, and sensible manner. The consanguineous couples must be referred to well before conception, especially when there is a family history of possible autosomal recessive conditions. They should be made to understand that nobody chooses to deliberately pass an illness to their offspring, and no one is to be blamed.

Goals of genetic counselling for consanguineous couples and their offspring

  • Providing preconception reproductive options
  • Improving pregnancy outcomes
  • Reducing morbidity and mortality
  • Knowledge about screening the new-borns.

CONCLUSION

Consanguinity is a common trend still followed in many countries. Thus, genetic counselling and Genetic Screening play an important role to control hereditary disorders. Parents especially those lacking formal education should get more awareness of consanguinity.

 

Health is wealth
Instead of creating a wealthy environment
We can create a diseases free environment for our future generation

 

References:

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  20. Hamamy H. (2012). Consanguineous marriages: Preconception consultation in primary health care settings. Journal of community genetics, 3(3), 185–192. https://doi.org/10.1007/s12687-011-0072-y

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