Understanding rare genetic skin disorders

According to World Health Organisation (WHO), the disorder prevalence of 1 or less per 1000 population is defined as rare diseases

October 14, 2021
Subhadeep Das and Biju Dharmapalan


Rare diseases or orphan diseases has minimal chances of occurrence in the human population which affects only small percentage of population. According to World Health Organisation (WHO), the disorder prevalence of 1 or less per 1000 population is defined as rare diseases. But in other countries such as Japan, the rare diseases prevalence is 1 in 2,500 population. Thus, the prevalence of rare diseases for different countries varies. There are more than 8000 rare diseases known worldwide, out of which only 450 have been identified in India. Rare diseases have emerged as a global public health concern. Over 350 million individuals are suffering worldwide; approximately over 30 million in USA, 30 million in Europe and 70 million in India. Around 7,26,11,605 individual is suffering from rare diseases in India. Organization for Rare Diseases India (ORDI) estimated that 1 in 5000 Indian is affected by rare diseases. Among the different Indian states, Uttar Pradesh has recorded highest number of rare diseases with 1,19,74,891 affected individuals and Sikkim with least count of approximately 36,461 individuals affected. About 40% of rare diseases is genetic in origin. The statistics suggest a significant problem of rare diseases in society.

Global Burden of Diseases (GBD) has ranked skin and subcutaneous diseases at 20th position among level 2 category for the cause of death globally. Recent report of Global Burden of Diseases (GBD) 2019, the rate of skin and subcutaneous diseases in India has recorded least in Sikkim with 458.07 DALY’s per 1,00,00 and highest in Odisha with 539.6 DALYs per 1,00,000. Rare genetic skin diseases is a sub-category under the skin and subcutaneous diseases which contribute to indefinite number of cases.

Rare genetic skin diseases

The skin is the largest organ in the body and functions as a defence mechanism against trauma, exhibiting versatile and rigid characteristics which are regulated by the types of molecules produced in each cell that enable cells to be properly integrated and communicated. The skin consists of a number of cell types that express specific molecules and also have distinct characteristics which promote the dynamic associations and intercellular interaction which are crucial to retaining the structural integrity of the skin.  Notably, the whole organisation and functioning of these networks may be disrupted by a single mutation in one of these biomolecules, leading to keratinisation disorder, distorted cell morphology, blistering, abnormal skin colour and other phenotypes identified in inherited skin disorders. The Johns Hopkins University’s Online Mendelian Inheritance in Man (OMIM) database has identified 560 distinct hereditary skin disorders associated with 501 unique proteins.

Abnormal skin colour has been observed in a various skin disorder with different molecular based causes. A number of factors, such as melanin, capillary blood flow, cutaneous chromophores (lycopene, carotene) and collagen in the dermis, affect skin coloration. Other significant factors such as physical factors, can also contribute to the abnormal skin colour, including the spectrum of light that affects the skin, the light reflected, refracted and absorbed, and the transparency of the stratum corneum and epidermis. For the most part, though the pigment system i.e. melanocytes and melanin, regulates the skin colour and is largely determined by the quantity, type and concentration of melanin within the skin. The functioning and distribution of pigment system is regulated by different genes. Any alteration in the gene expression that contribute to the normal colour of the skin, results in abundance or deficiency within the skin will cause an abnormal colour of the skin. A broad range of symptoms and signs that differ from not only disease to disease, as well as from patient-to-patient suffering from same disease describe rare genetic skin diseases.

Individuals with rare diseases may face difficulties that are different from those experienced in more common medical conditions. The emergence of common symptoms similar to other medical condition might lead to disguising the underlying rare genetic skin diseases results in misdiagnosis and delay in treatment. Due to the low prevalence of rare genetic skin disease result in rare medical expertise, limited knowledge about the condition, inadequate care offerings and limited research. Psychological constraints were identified in adults with rare genetic skin diseases, such as incapability of decision making and behavioural change. Diagnosing hereditary skin disorders is still a challenging task due to their rarity, diversity and diseases evolving over many years.(Full article available in the pdf)