Archives of Medicine and Health Sciences

: 2016  |  Volume : 4  |  Issue : 1  |  Page : 50--57

Sickle cell disease genetic counseling and testing: A review

John C Aneke, Chide E Okocha 
 Department of Haematology and Blood Transfusion, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

Correspondence Address:
John C Aneke
Department of Haematology and Blood Transfusion, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra State


The huge burden of sickle cell disease (SCD) coupled with a correspondingly high morbidity and mortality, particularly in Sub-Saharan Africa, has made it really imperative to invest more in ways of reducing the prevalence of this disorder. The SCD genetic counseling and testing have been shown to educate individuals on SCD and also offer those at risk the opportunity of making informed decisions on marriage and pregnancy. We reviewed available data on genetic counseling and testing for SCD, using the PubMed, PubMed Central, Google Scholar, and African Index Medicus search engines, through a combination of words and phrases relevant to the subject and attempted to highlight how this can be better applied in a resource-poor setting such as Nigeria, with a huge disease burden. More advanced countries with significant population of patients with SCD and other hemoglobinopathies have evolved functional genetic and counseling protocols, with remarkable impacts on disease epidemiology; this feat however does not appear to be replicated in a number of African countries. This paper reviewed genetic counseling and testing for SCD in countries with high disease burden, with particular emphasis on Nigeria, which has a disease prevalence and carrier rate of 2-3% and 20-30%, respectively.

How to cite this article:
Aneke JC, Okocha CE. Sickle cell disease genetic counseling and testing: A review.Arch Med Health Sci 2016;4:50-57

How to cite this URL:
Aneke JC, Okocha CE. Sickle cell disease genetic counseling and testing: A review. Arch Med Health Sci [serial online] 2016 [cited 2020 Oct 22 ];4:50-57
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Sickle cell disease (SCD) is a group of inherited disorders of hemoglobin (Hb) in which the sickle Hb is present in association with abnormal Hb.[1] It is the most common single gene disorder in the world and up to 312,000 people are born yearly with HbSS globally; majority of these births (236,000) occur in Sub-Saharan Africa.[2],[3] Historically, the homozygous HbSS disease, HbSβ-thalassaemia (HbSβ-Thal), HbS plus C, D, and E (HbSC, HbSD, and HbSE, respectively) are commonly included under the classification of SCD.[4] The geographical distribution of these Hb variants differs and often parallels certain attributes such as climatic conditions and malaria endemicity. While the HbSS and HbSC diseases are highly prevalent in areas of Sub-Saharan Africa, particularly West Africa, the HbSβ-Thal, HbSD and HbSE are more common in parts of the Middle East and Asia.[5],[6],[7],[8],[9],[10] The prevalence of the carrier rates for HbS ranges from 5% to 40% among populations in these endemic areas; this thus drives disease epidemiology.[11]

The HbSS disease (sickle cell anemia) is the most common of the Hb variant and results from a GAG→GTG nucleotide switch with a resultant substitution of valine for glutamine in the position 6 of the β-globin chain of Hb.[12],[13] This creates a very significant functional defect in the Hb molecule, leading to polymerization, red cell shape change (sickling), interaction with vascular endothelium, white cells (particularly neutrophils), and platelets. The adherence of sickle red cells to the endothelium and other cellular elements of blood leads to vascular stasis, ischemia, more red cell sickling, and ultimately end organ dysfunction.[14],[15],[16] Correspondingly, the Hbs C, D, and E result from β6 Glu→Lys, β121 Glu→Gln, and β26 Glu→Lys amino acid substitutions, respectively.[17],[18],[19],[20],[21] The thalassaemia syndrome results from genetic defects in α or β globin gene loci with absent or reduced synthesis of one or more globin chains.[22],[23] The HbSβ-Thal syndrome therefore results from the co-inheritance of the sickle and thalassaemia mutations; this may clinically manifest as homozygous HbSS disease.[24]

The burden of SCD is huge, particularly in Nigeria and Sub-Saharan Africa, resulting in poor quality of life, with attendant loss of labor man hours and strain on health facilities. The prevalence of SCD in Nigeria has been variously reported to be in the range of 2–3% while the asymptomatic carriage rate currently stands between 20% and 30%.[25],[26],[27] Against a backdrop of a huge infrastructural deficit, the mortality from SCD, particularly in under-five, remains unacceptably high. Recent estimates have shown that without timely and adequate intervention, up to 90% of affected children will die before the age of 5.[28],[29] Commonly, organ-system dysfunction including mainly renal,[30] cardiovascular,[31],[32] and cerebrovascular [33],[34] occur earlier and at a higher frequency in SCD patients than Hb AA controls and is an important contributor to early death.

The treatment of SCD patients has continued to improve tremendously, especially in the last decade; it however remains poor in Nigeria and most African countries. While hydroxycarbamide has been recognized as an important component of the treatment of patients with SCD and has indeed found wide usage in developed countries, it is just becoming popular in a number of African countries.[35],[36] It is yet to be seen how the use of hydroxycarbamide will impact on the African patient with SCD, in view of the huge heterogeneity in clinical phenotypes of the disease.[37],[38] Some researchers had earlier feared that the cost implication for the patient in fact, in the long run, could constitute a hindrance to the universal adoption of this treatment modality in Africa, recent evidence appeared to support this line of thought and indeed revealed a very suboptimal access to this drug in West Africa.[39] Even though stem cell transplantation has been shown to achieve cure in SCD in a number of series,[40],[41],[42] this novel treatment is presently beyond the majority of African patients due to a combination of cost implications and infrastructural inadequacies.

It is obvious that at present, the social and health systems in Sub-Saharan Africa have been largely overwhelmed by the huge burden of SCD-related complications, with attendant significant morbidity and mortality. These observations have therefore made it very imperative to intensify efforts at reducing the prevalence of the sickle gene through a number of epidemiological interventions, such as the establishment of a viable sickle genetic counseling clinic, backed by an equally robust laboratory diagnostic facility in Nigeria and Sub-Saharan Africa.

We searched PubMed, PubMed Central, Google Scholar, and the African Index Medicus electronic databases, using a number of word and phrase combinations such as “'sickle cell disease,” “genetic testing,” “genetic counseling,” “premarital testing,” “epidemiology of hemoglobinopathies,” “developing countries,” and “Nigeria.” The information from these publications was discussed in this review and recommendations made toward establishing vibrant and country-wide sickle cell genetic counseling and testing centers in Nigeria.

 A Brief Epidemiology of Sickle Cell Disease

The World Health Organization recently published a prevalence map of SCD which showed that about 20-25 million people globally have HbSS, of this about 12-15 million live in Sub-Saharan Africa, 5-10 million live in the Indian subcontinent while about 3 million others are distributed in other regions of the world.[43]

The distribution of the sickle gene in Africa [Figure 1][44] reflects a very close parallel with the endemicity of malaria, particularly that due to Plasmodium falciparum . The highest frequency of the sickle gene in Africa has been traced to the low altitude, tropical areas with significant amounts of rainfall annually.[45] The remarkable parallel noted between the prevalence of P. falciparum malaria, and the distribution of Hb S, β-, and α-thalassemia was beautifully enunciated by Halden in 1949 and pointed toward some survival advantage (to severe malaria) provided by heterozygosity to the sickle mutation; this has been termed “balanced polymorphism.”[46] The compound heterozygous HbSC is commonly seen in parts of Africa (next in frequency to the homozygous HbSS state); it represents a milder disease phenotype and occurs predominantly in people of West African origin. The HbSβ-Thal disease is generally not believed to be present in significant numbers in Africa, mainly confined to parts of Asia and Middle East.[47] In other parts of Africa (South, East, and Central Africa), the epidemiology of SCD appears to exclusively mirror that of the homozygous HbSS state, as the other Hb variants are rarely encountered. Interestingly, the world has encountered massive globalization, migration and changes in population dynamics, in such an unprecedented scale in the past; this has significantly impacted on the epidemiology of SCD. A country such as the United States of America (USA), which is not known to be endemic to malaria, has a significant population of SCD patients. It is estimated that up to 100,000 of SCD subjects live in the USA.[48] Apart from the influence of malaria endemicity in maintaining the presence of the sickle gene in a population, other possible contributors have been recently highlighted, including high rates of consanguineous marriages,[49] epidemiological transition with improved longevity,[50] and founder effects of original inhabitants.[50]{Figure 1}

 Sickle Cell Disease Genetic Counseling and Testing in Countries With Significant Burden

In countries with universal genetic counseling and screening for endemic-inherited disorders, information gathered from such exercise not only gives insight into the epidemiology of these disorders but also could most importantly be a useful resource for health planning in such countries.[10],[51] An increasing body of evidence has shown that premarital counseling and testing can indeed reduce the prevalence of inherited disorders of Hb, principally by identifying and offering counseling to intending couples of high-risk marriages.[52],[53] Importantly, premarital counseling has been shown to have a significant advantage over neonatal screening in that while it is aimed toward primary prevention, the latter addresses secondary, or tertiary prevention (after the deed has been done).[54] A number of the Mediterranean and the Middle Eastern countries have developed effective premarital counseling and testing protocols with a view to reducing high-risk marriages, with some interesting results.[49],51,[55],[56],[57]

Saudi Arabia has a significant burden of SCD and thalassaemia; prevalence rates of 4.2%, 0.26%, and 3.22% were reported for Hb AS, SCD, and β-thalassaemia, respectively in 2007.[10] In a bid to reduce the huge burden on health care as well as the negative impact on the quality of life of patients, premarital genetic screening for hemoglobinopathies was made mandatory in the country since the year 2004.[58] The impact of this has been quite remarkable, particularly with regards to showing the epidemiology of these disorders in the country and emphasizing areas that need more concerted attention and actions. A study by Memish and Saeedi observed a steady decrease from 32.9 to 9.0 per 1000 examined persons, following 6 years of premarital screening for hemoglobinopathies.[49] The study equally reported a 5-fold increase in voluntary cancellation of marriage proposals among at-risk couples, during the study period.[49] A similar study done at about the same time showed that couples with prior knowledge of their Hb genotype had more chances of avoiding high-risk marriages compared with controls 28.8% (30/104) versus 18% (86/478) and emphasized the importance of strengthening existing screening systems.[55] Earlier study by Alhamdan et al. showed an excellent access of target populations to genetic counseling and testing; the study however failed to show a significant reduction in the frequency of marriages between at-risk couples, this is probably due to the fact that this report was made just 3 years following the commencement of universal screening and testing, before any significant change could have occurred.[10] The authors advocated improvement in education programs as well as changes in the strategy of timing of screening in relation to marriage.[10] In other Middle Eastern regions, premarital genetic counseling and testing have been documented to significantly decrease the prevalence of hemoglobinopathies in Iran,[59] Turkey,[60] and Bahrain.[61]

A number of countries in the Mediterranean region have equally evolved a very efficient genetic counseling and testing model for hemoglobinopathies. The success story of premarital genetic testing in the Mediterranean countries of Greece, Cyprus, and Italy was nicely chronicled in the report of Cao et al. , with emphasis on prospects such as automation of mutation detection, introduction of preconception and pre-implantation diagnosis, and diagnosis by analysis of fetal cells in maternal circulation.[57] In Cyprus in particular, the religious bodies play very significant roles in enforcing mandatory premarital testing and give appropriate counseling to at-risk individuals with very remarkable results.[62],[63],[64]

As early as 1988 and 1992, Anionwu et al. and Petrou et al . independently confirmed the importance of detecting and counseling couples at risk before pregnancy and equally emphasized the great opportunity prenatal counseling and testing could present to couples by helping them make informed decisions on marriage and pregnancies in the United Kingdom (UK).[65],[66] Following the adoption of the NHS Plan of 2000 in the UK, the sickle cell and thalassaemia program came to the mainstream with the objective of offering timely screening for SCD and thalassaemia to all women in the antenatal period, to enable informed decision-making.[67],[68] The guideline supporting this plan stipulates that the screening process should take place within the first trimester,[69],[70] with both screening and prenatal diagnosis (PND) concluded and any further line of action completed by the end of the 12th week of gestation.[68] There is however increasing evidence that the first-trimester window mandated for genetic screening and testing for at-risk groups is not strictly complied with. A recent survey discovered that up to 95% of antenatal women in the UK were not screened for sickle cell anemia or thalassaemia within the first-trimester target.[71] Tsianakas et al. evaluated the impediments to timely application of genetic counseling and testing for hemoglobinopathies in the UK population and identified professional, organizational, and patient-related barriers against early testing.[72] These findings were equally corroborated by Dormandy et al. , who advocated the strengthening of methods of organizing and delivering antenatal care, with a view to facilitating earlier screening of all at-risk groups in the UK.[73]

In the USA, with an equally significant burden of SCD, genetic counseling and testing have been well established as early as 1970 and this has shown remarkable promise in reducing the chances of at-risk couples giving birth to affected children.[48],[74],[75] Wang et al. performed PND for SCD in 500 pregnancies and observed termination of pregnancy (TOP) rates of 51% and 12% in affected pregnancies with HbSS and HbSC fetuses, respectively.[76] In addition, the study reported that the gestational age at the time of screening had a significant influence on maternal decision to terminate pregnancies, particularly when the fetal diagnosis was HbSS.[76]

Antenatal screening programs for hemoglobinopathies, which is based on ethnic origin, have been similarly introduced in a number of European countries including Holland, Belgium, and Germany.[77]

The sickle gene has been shown to be prevalent in parts of the Indian sub-continent, the Arab-Indian haplotype predominate in these populations, and most affected individuals exhibit a severe disease phenotype.[78] Jain et al. reported birth rate of 1.1% for SCA in Central India, with the highest incidence observed among populations in Mahar community (2.0%).[79] In addition, a significantly high incidence (up to 1:50) was similarly identified in some tribal groups such as the Scheduled caste groups and other groups with low socioeconomic status.[79] A high carrier frequency of HbS (40%) is reported to be largely responsible for the high population prevalence of SCD in India.[80]

In western part of the country, Italia et al. screened 5467 newborn babies for SCD among tribal populations and reported prevalence rates of 0.6%, 0.23%, and 12.5% for SCA, sickle-β-thalassaemia, and sickle heterozygous phenotypes, respectively.[81] The authors in addition emphasized the need for increased awareness of SCD and advocated regular screening and monitoring of affected babies to reduce disease-related morbidity and mortality in these populations.[81]

Genetic counseling for SCD has been shown to enjoy huge acceptance in parts of India; success rate of up to 50% has been reported in tribal areas, after a 5-year follow-up period.[82] Consistent application of genetic counseling coupled with the establishment of permanent centers for this is advocated to be vital in reducing the prevalence of SCD in the Indian population.[82]

Experience in Nigeria

Genetic counseling and testing have been sparsely reported in Nigeria; the pioneer work by Akinyanju et al. in 1999 highlighted the need for a country-wide application of this program.[83] In the above study, genetic counseling and subsequently PND were offered to 124 women (51% had previously had children with sickle-cell anemia) in Lagos, Southwest Nigeria, and showed a carriage rate of 18.5% for HbSS among the fetuses; 96% of these fetuses were subsequently aborted.[83] The high abortion rate in this study could be attributable to the discrepancy between the perceptions of the “power to cure” by doctors and the “power to care” by parents and intending mothers as was beautifully described by Wonkam and Hurst, recently.[84] This phenomenon occurs because the belief by doctors and health care providers in their ability to adequately cater for patients with SCD is higher than the belief in the mothers that the care given by medical personnel will be really adequate to take care of a child with SCD. In a Nigerian report, 92% of the SCD heterozygous carrier mothers and 85% of female SCD patients agreed to take PND; out of this, 63% of mothers and 35% patients signified a willingness to undergo a TOP if they have an affected pregnancy.[85] In contrast, only 21.4% of Nigerian doctors would consent to perform a TOP for an affected pregnancy with SCD.[86] Adeola Animasahun et al. similarly reiterated these observations in a recent study among health professionals at the Lagos University Teaching Hospital, Lagos, Nigeria; only 33% agreed to offer TOP to mothers if prenatal screening confirms SCD.[87] A very recent study in Ekiti and Ibadan captured the huge financial implications of caring and catering for a child with SCD in Nigeria, which is worsened by the out-of-pocket module of health care financing currently operational in the country.[88],[89],[90],[91] It is therefore very likely that this could well be reason why the mothers could not believe in the “power to cure” of the doctors and showed a higher preference for TOP, after genetic counseling and testing. Nnaji et al. had evaluated the attitude of couples who were at risk of having offsprings with SCD in Nnewi, Southeast Nigeria, and reported that up to 2/3 of these would call off their marriages if there was risk of their children inheriting the disease.[92] This therefore implies that premarital SCD genetic counseling and testing (if correctly applied in Nigeria) has the potential to reduce the frequency of births to affected children and in the longer term the prevalence of this disease.

Earlier studies have suggested that actual counseling and testing for SCD in Nigeria were done mainly by religious bodies, as part of premarital requirements, akin to the Cypriot model.[93],[94] This may thus explain the paucity of literature from Nigeria on this subject. It is not absolutely clear how effective this religious body-based model is in Nigeria; the quality of counseling offered to intending couples vis-a-vis that expected by scientific standards. It is therefore really imperative that doctors and other health care professionals should take up this challenge in Nigeria or at the least establish very robust partnerships with the religious bodies in this matter. This will ensure that proper genetic counseling and scientific testing for SCD (in line with global best practices) are given to all at-risk individuals and importantly, that everyone is given the privilege to make informed (voluntary) decisions based on the results of such tests. It is indeed reassuring to note that the Sickle Cell Support Society of Nigeria (a coalition of physicians with interest in SCD in Nigeria) is currently in the forefront of efforts to streamline and expand the early diagnosis of SCD in Nigeria.[95] It is hoped that the vision of this organization will translate to tangible programs which will enhance counseling and testing for SCD in the country.


The current utilization of genetic counseling and testing for SCD in Nigeria is unacceptably low, in view of the high prevalence of this disorder in Nigeria. This will not only adversely affect health policy planning but also could in addition continue to fuel the already high carriage rate of the S gene in the country, with attendant high morbidity and mortality in individuals born with the disease.

The following need to be urgently addressed by health policy makers in Nigeria to address this huge deficit;

Country-wide provision of adequate infrastructure (including facilities for carrying out polymerase chain reaction) to enable proper testing,Massive education of the populace to increase the understanding of SCD and the need for voluntary testing, particularly in at-risk groups,Strengthening existing facilities for managing SCD patients in Nigerian hospitals and providing health insurance to affected groups, with a view to possibly reducing the “power to cure” and “power to care” gap.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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