Pachyonychia congenita


Pachyonychia congenita

Description, Causes and Risk Factors:

Abbreviation: PC.

Pachyonychia congenita is a group of rare, inherited ectodermal dysplasias whose most prominent clinical feature is hypertrophic nail dystrophy. Two main clinical variants of pachyonychia congenita are recognized, pachyonychia congenita type 1 and pachyonychia congenita, type 2.

Pachyonychia congenita affects both males and females. No ethnic differences have been reported. Approximately 400 cases (confirmed by mutation analysis) have been identified; another few hundred unconfirmed cases have also been identified. Some researchers believe that Pachyonychia congenita often goes misdiagnosed or undiagnosed making it difficult to determine the true frequency of PC in the general population.

Mutations in KRT6A (which codes for keratin K6a) or KRT16 (encoding K16) cause Pachyonychia congenita type I and mutations in KRT6B (encoding K6b) or KRT17 (coding for K17) result in Pachyonychia congenita type II. The majority of mutations are heterozygous single base pair changes resulting in an amino acid change (missense mutations) although some small in-frame deletion/insertion mutations (deletion/insertion of base pairs results in deletion/insertion of one or more amino acids) have been reported.

Most mutations occur in regions of the keratin proteins known to be important for the structural function of keratins. There are some mutations that are found in several families (recurrent mutations). Other more rare mutations have only been observed in single families to date. One common site for mutation in K6a is amino acid N171, which is either deleted or a single base pair is changed (mutated) resulting in an amino acid change. In Pachyonychia congenita type II there are several recurrent mutations in KRT17, particularly N92S.

Symptoms:

Symptoms may include:

    Thickened fingernails and toenails.

  • Plantar keratoderma - blisters and thick calluses on the soles of the feet.

  • Palmar keratoderma - blisters and thick calluses on the palms of the hands.

  • Oral leukokeratosis - thick white growths on the tongue and the insides of the cheeks.

  • Follicular keratoses - bumps that form around the hair follicles.

  • Possible involvement of the larynx - hoarseness or thickening of the voice box.

  • Hyperhidrosis (excessive sweating) and non epidermal cysts.

  • Natal or prenatal teeth.

  • Cysts - including steatocystoma (epithelial/skin) type.

Diagnosis:

Pachyonychia congenita should be differentiated from traumatic thickening of nails and from congenital onychogryphosis

Pachyonychia congenita is diagnosed by its clinical appearance. Skin biopsies of the affected tissues will only show nonspecific changes. Molecular genetic studies can be done by specialist laboratories to detect mutations in the affected keratin genes.

Antenatal molecular diagnosis is feasible provided the causative mutation is known. Recent data suggesting the possibility that the disease may rarely be inherited in a semi-dominant fashion emphasizes the importance of accurate molecular diagnosis for proper genetic counseling.

Treatment:

There is no curative treatment for pachyonychia congenita yet. Treatment of manifestations will focus primarily on grooming of nails and management of pain due to palmoplantar keratoderma. Treatment of Pachyonychia congenita is primarily symptomatic. Emollients (moisturizers) and keratolytics (products containing alpha-hydroxy acids) can be used for the hyperkeratosis. Routine grinding of the nail plates can minimize their interference with function. Severe cases can be treated systemically with oral synthetic retinoids (Accutane, Soriatane). Retinoids are only used in severe cases due to their known bone toxicity and other complications.

Novel treatment modalities under investigation include small interfering RNA (siRNA) strategies, the use of systemic and topical rapamycin, and injection of botulinum toxin. Clinical studies based on library screening of existing drugs are ongoing. Complications may include secondary infection that is usually well controlled by antibiotics therapy.

The only effective treatment for nail lesions is surgery with radical excision of the nail, nail bed, and nail matrix and skin implantation at the site of the removed nail.

Surgical treatment is also important in case of oral lesions with hoarseness or respiratory problems. Airway obstruction, due to leukokeratosis, can in fact lead to severe respiratory distress.

NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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