Written by: Lucky Annem
Medically reviewed by: Dr. Lohi Pratti
Pachyonychia congenita (PC) is a rare genetic disorder that primarily affects the skin, nails, and mucous membranes. It is characterized by the presence of thickened nails (pachyonychia) and various other symptoms. Pachyonychia congenita is caused by mutations in genes that provide instructions for producing proteins known as keratins. There are five types of pachyonychia congenita, each associated with different gene mutations. The most common types are PC-1 and PC-2. PC-1 is caused by mutations in the KRT6A gene, while PC-2 is caused by mutations in the KRT16 gene. These genes provide instructions for producing keratin proteins that are primarily found in the skin and nails.
The mutations in the KRT6A and KRT16 genes lead to the production of abnormal keratin proteins or disrupt the normal production of these proteins. As a result, the structural integrity of the skin, nails, and mucous membranes is compromised. The exact mechanisms by which these mutations cause the specific symptoms of pachyonychia congenita are not fully understood but are believed to involve the disruption of cell-to-cell adhesion, cellular signaling pathways, and the regulation of keratinocyte differentiation. Pachyonychia congenita is inherited in an autosomal dominant manner. The offspring of an affected individual have a 50% chance of inheriting the disorder. If the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk is possible.
The effects of pachyonychia congenita can vary from mild to severe. Individuals with PC often experience thickened nails (onychogryposis) that can be painful and prone to infections. They may also have blistering and calluses on the soles of their feet (plantar keratoderma) and thickened patches of skin on their palms (palmar keratoderma). Other common symptoms include sweating abnormalities and hair abnormalities. Oral lesions, namely oral leukokeratosis (thickened white patches on the tongue and cheek), are often present as well. In babies, oral leukokeratosis may cause difficulty in sucking. These physical manifestations can significantly impact an individual's quality of life and daily functioning.
From a scientific perspective, studying pachyonychia congenita can provide valuable insights into the role of keratins in maintaining the integrity of the skin, nails, and mucous membranes. The disorder highlights the importance of understanding the underlying mechanisms of keratin-related diseases and may contribute to advancements in dermatology and genetic research.
The prognosis for individuals with pachyonychia congenita varies depending on the severity of symptoms. While there is currently no cure for PC, management strategies focus on alleviating symptoms and improving quality of life. Treatment options may include regular nail trimming, topical creams to reduce inflammation, the use of orthopedic devices to manage foot pain, and counseling for psychological support. Attention to pre- and post-grooming hygiene is a critical aspect of preventing infection with this disease; some may benefit from a very diluted ‘bleach bath’ to help prevent infection. Pain from palmoplantar keratoderma may be somewhat alleviated by reducing friction and trauma to the feet by avoiding prolonged standing or walking, decreasing hydration of the stratum corneum by wearing wicking socks and ventilated footwear, choosing supportive shoes, and maintaining healthy body weight. Foot care comprises reducing hyperkeratotic lesions and applying topical treatments (emollients and lotions containing keratolytic) for hyperkeratosis. High temperatures and high humidity may worsen the condition, so avoiding hot and muggy weather conditions is a component of managing this condition. Additionally, genetic counseling and family support are crucial for affected individuals and their families, as pachyonychia congenita can have a significant impact on their emotional well-being.
There have been advancements in targeted therapies for pachyonychia congenita. Experimental treatments, such as RNA interference (RNAi) therapy, have shown promising results in preclinical studies by reducing the expression of mutant keratins and alleviating symptoms. These advancements offer hope for the development of more effective and targeted treatments in the future.
Pachyonychia congenita is a rare genetic disorder characterized by thickened nails, skin abnormalities, and mucous membrane involvement. It is caused by mutations in specific keratin genes, disrupting their normal functioning. Pachyonychia congenita poses challenges for affected individuals, but ongoing research and advances in treatment options hold promise for improving their quality of life. Understanding this disorder and its underlying mechanisms can contribute to scientific advancements in dermatology and genetics, potentially benefiting not only those with pachyonychia congenita but also individuals with other keratin-related conditions.
Image Source: Leachman et al.
References:
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NIAMS. “Pachyonychia Congenita.” National Institute of Arthritis and Musculoskeletal and Skin Diseases, 14 Nov. 2015, www.niams.nih.gov/health-topics/pachyonychia-congenita#:~:text=Pachyonychia%20congenita%20is%20caused%20by,skin%20cells%20strength%20and%20resilience. Accessed 6 May 2023.
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“Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC) - Full Text View - ClinicalTrials.gov.” Clinicaltrials.gov, 2023, clinicaltrials.gov/ct2/show/NCT02152007. Accessed 6 May 2023.
“UpToDate.” Uptodate.com, 2023, www.uptodate.com/contents/pachyonychia-congenita. Accessed 6 May 2023.
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