Most of the genetic disorders are rare. Though the definition for ‘rare disorders’ varies in different countries, the
basic premise is that they are not common. The other aspect about rare disorders is that most of them
do not have curative treatment. Except Down syndrome and beta thalassemia, even the commonest of
the genetic disorders like Hemophilia and Duchenne muscular dystrophy have prevalence of about 1 in
5000-10000 live births. Because of their relatively low prevalence, these disorders tend to get ignored by
clinicians, the government, researchers and pharmaceutical companies. But the scenario is changing all
over the world. The advent of new therapies and a lot of ongoing research suggest hope for many genetic
disorders. The Human Genome Project and newer genomic technologies are primarily responsible for this
progress. Very rapid identification of causative genes is leading to better understanding of the molecular
pathophysiology of genetic disorders and this is a sure step towards the development of novel therapies for these
conditions. An article on the genetics of Coffin Siris syndrome in this issue is representative of the research on
monogenic disorders in the twenty-first century. Whole exome sequencing can identify the causative gene in a
single case or a few cases in a nuclear family. After identifying the first causative gene, other genes in the
SWI/ SNF chromatin modeling pathway were identified as causes of Coffin Siris syndrome and similar
phenotypes. The same strategy is being used in clinical settings for diagnosis of rare syndromes where a clinical
diagnosis is next to impossible. The use of exome sequencing for newborn screening is now being explored
and early experiences and issues involved in this strategy have been reviewed in the article on NGS-based
newborn screening. The GenExpress in this issue gives glimpses of the use of genomic techniques like next
generation sequencing and microarray in prenatal diagnosis. The very high sensitivity of diagnosis of fetal
aneuploidies, microdeletion syndromes and monogenic disorders like achondroplasia and Duchenne muscular
dystrophy through analysis of free fetal DNA in maternal plasma is impressive and a revolution in prenatal
diagnosis.
These recent developments in rare disorders are relevant to Indian clinicians and the general population at this
juncture, when India is stepping towards being a developed nation. Infectious and nutritional disorders in children are
getting controlled. Secondly, medical genetics has taken a strong foothold in India. Though the numbers are still small,
state-of-the-art clinical and diagnostic facilities have been established in many centers in India. Due to the large
population, even rare disorders are seen in significant numbers in India.
To take advantage of this and to help patients and families with genetic disorders, recently a Workshop for Research
in Rare Disorders was organized in New Delhi. The stakeholders in the area discussed various issues and
presented the work done in this area. The funding being provided by the governments of some states for free
treatment of hemophilias and thalassemia / hemoglobinopathies was acknowledged to be a commendable
and important endeavour. These two disorders are the commoner of the genetic disorders and have very
good outcome with timely and appropriate treatment. Established patient support groups working for
decades for these two disorders have been instrumental in getting government funding for these drugs.
This experience will help in future policy decisions and planning for similar government support for other
less common genetic conditions as well. The new treatment options are coming and awareness about rare
disorders among the policymakers and health administrators created by thalassemia and hemophilias will
definitely work in a positive way. In addition to awareness and empathy of clinicians and the government,
registries of rare diseases, electronic health records linked to the unique identity, a tiered referral system,
population based pilot programs for prevalence studies and a law to take care of rare diseases are some
other actions needed to start work in this direction. Parallel to the patient care activities, research efforts
need to be planned in a systematic and planned way as a coordinated effort. The research component for
understanding the pathogenesis of various genetic disorders using the vast clinical material in India is one
aspect, the other being indigenous drug development as many novel therapies initiated by the developed
world are beyond the reach of Indians. All these issues were outlined in the Workshop. I am sure the group
will formulate a definite workplan and also will be a mediator to send the correct message and provide
guidance to the government. This century is bound to bring a paradigm change in the health policies for rare
disorders.
