What Is De Sanctis Cacchione Syndrome

Introduction

De Sanctis-Cacchione (DSC) syndrome is an extremely rare autosomal recessive disorder that has been classified as an extreme symptom of Xeroderma Pigmentosum (XP).^1,2 XP is a condition that causes a heightened sensitivity to light, particularly (ultraviolet) UV radiation from the sun. This abnormal sensitivity can lead to various medical issues, including skin cancer and photophobia. In addition to the manifestations of XP, individuals with DSC also present with about two or more neurological disorders, hence why it is an extreme case of XP.

Understanding DSC is crucial for early diagnosis, research into the underlying causes, and boosting awareness and the availability of support services for this condition. Patients with DSC and their families are more likely to benefit from the support and information that enables them to manage the syndrome’s symptoms. The purpose of this article is to highlight the relevant knowledge relating to DSC. Understanding the causes, symptoms, and treatment of DSC will help raise awareness and provide information to the individuals who are in question.

Historical background

DSC was an evolution from XP. Moriz Kaposi first described XP in patients in one of his dermatology textbooks in the 1870s.³ Later on, in 1932, De Sanctis and Cacchione described the features present in XP alongside mental deficiency, dwarfism, and progressive neurodegeneration in brothers from the same family.^3,4This is why the severe phenotype, which is rare, was named the De Sanctis-Cacchione syndrome.

What causes de sanctis cacchione syndrome?

There is a pathway known as the nucleotide excision repair (NER) pathway in our bodies that is responsible for repairing the damage done to DNA building blocks. This damage is usually due to UV light, particularly from the sun. In patients with DSC and XP, there is a mutation in the genes that are responsible for activating the NER pathway therefore there is a reduced capacity of repairing DNA.5 The genetic mutation can be passed on from parent to offspring. Some individuals have one normal gene and one DSC syndrome gene, which makes them carriers of the disease; hence, it is important to do genetic testing before starting the journey of bringing a child into the world. When both parents are carriers, there is a 25% chance of passing on DSC with each pregnancy.

Other researchers have generated the theory that DSC is a form of a chromosomal abnormality. Chromosomal abnormalities can arise from environmental factors; in this case, that could be UV radiation or the possibility of missing chromosomes. Females have XX chromosomes, whereas males possess XY, meaning they do not have the other long arm. The theory states that DSC is caused by a disruption of the gene located on the long arm of the chromosome.¹⁰ This is a possible cause that is still being researched; however, up to date, there has been no correlation between gender and DSC syndrome progression, only the mere factor that it is most likely to be seen in children.

What are the clinical features of DSC?

Patients with DSC also present with XP symptoms. The symptoms of XP include

• Eye surface cancers,
• Photophobia (eye sensitivity to bright light),
• Freckles from an early age (usually under 2),
• Skin atrophy (degeneration of the skin or thinning of the skin),
• Precancerous skin lesions,
• Dry, blistered or patches of skin and
• Inflammation of corneas.^6,7

For DSC patients, there are other skin symptoms like hyper or hypopigmentation, loss of skin colour, scarring of the skin, wart-like lesions, and easily bruised skin. In addition to the skin symptoms, DSC individuals have:

• One or more neurological abnormalities (usually low intelligence),
• Microcephaly (small head),
• Mearing impairment,
• Weak reflexes,
• Limited movement
• Involuntary movements (such as uncontrolled jerks), and
• Eyesight abnormalities.²

It is important to note that symptoms of DSC present differently in each individual therefore medical professionals can be the only ones that can diagnose the syndrome.

Diagnosis and screening

De Sanctis-Cacchione syndrome is usually diagnosed following an XP diagnosis. A clinical evaluation can include the use of autoradiography⁸ and imaging studies like MRIs and CT scans. This evaluation will determine the presence of any neurological abnormalities. In addition to the scans, laboratory tests can be done to check lymphocytes and other cells in the body. The results may show cells exposed to UV light and carcinogens (cancer-producing cells).

It is possible to validate the existence of mutations in the genes linked to De Sanctis-Cacchione syndrome using genetic testing, more precisely, DNA sequencing. ERCC6 mutations are frequently to blame for DSC. For an exact diagnosis, certain mutations must be confirmed. Genetic counselling can be given to those affected and their families after the mutations are detected. Understanding the syndrome's pattern of inheritance and the dangers of passing it on to future generations is made easier with the aid of this counselling. Now, in cases where a family has a history of De Sanctis-Cacchione syndrome or carries the gene, prenatal testing can be offered to expectant parents. This allows them to make informed decisions about the pregnancy, including possible interventions and future family planning.⁷

Treatment and management

Individuals with De Sanctis-Cacchione syndrome may face challenges, but there are management and treatment options available. By taking proactive measures such as protecting their skin from sunlight, limiting outdoor activities during daylight hours, and avoiding chemical carcinogens, affected individuals can help prevent the development of skin lesions and other complications. Early detection and surgical removal of skin cancer lesions is essential, and regular skin and eye examinations can help ensure overall health. Remember, with the right care and attention, individuals with DSC can live happy and fulfilling lives.

It's great to know that having information about the specific genetic mutations associated with De Sanctis-Cacchione syndrome can be helpful in personalizing the treatment and management of the condition. While there might not be a cure for the syndrome, having genetic information can guide healthcare providers in creating a tailored care plan that addresses the specific needs and risks associated with the patient's mutations. Additionally, genetic testing results can help determine the frequency and intensity of medical surveillance needed to manage the syndrome effectively.^1,7

Summary

De Sanctis-Cacchione Syndrome is a genetic disorder that can be confidently diagnosed through genetic testing, which not only confirms the syndrome's presence but also aids in early diagnosis. This allows for timely interventions and personalized management plans, ensuring the best possible outcomes for patients. Genetic counselling is highly recommended for patients and their families to understand the hereditary aspects of the syndrome, make informed family planning decisions, and reduce the risk of passing it on to future generations. Due to their heightened sensitivity to UV radiation, individuals with the syndrome require regular monitoring for skin cancer, eye abnormalities, and neurological issues. The specific genetic mutations may dictate the type and frequency of screenings needed to ensure the best possible care. Patients' genetic data can contribute significantly to ongoing research, potentially leading to targeted therapies and interventions in the future. Clinical trials may also provide hope for improved treatments, and we encourage patients to participate in these trials to advance our understanding of the syndrome.