What is pachyonychia congenita?

Pachyonychia congenita is a condition that primarily affects the nails and skin. The signs and symptoms of this condition usually become apparent within the first few months of life, although a rare form of the condition known as pachyonychia congenita tarda appears in adolescence or early adulthood. Almost everyone with pachyonychia congenita has hypertrophic nail dystrophy, which causes the fingernails and toenails to become thickened and abnormally shaped. Many affected children also develop very painful calluses and blisters on the soles of the feet and, less commonly, on the palms of the hands. This condition is known as palmoplantar keratoderma. The blistering is most severe in weight-bearing areas and in other areas that experience trauma or friction. Severe blistering and callusing on the feet can make it painful or impossible to walk. Additional features of pachyonychia congenita include thick, white patches on the tongue and inside of the cheeks (oral leukokeratosis); bumps called follicular keratoses that develop around hair follicles on the elbows, knees, and waistline; cysts in the armpits, groin, back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis). Rarely, the condition can affect the voicebox (larynx), potentially leading to hoarseness or breathing problems. These features vary among affected individuals. Researchers have described two major forms of pachyonychia congenita, type 1 (PC1) and type 2 (PC-2). The two types are distinguished by their genetic cause and by their signs and symptoms. Both types are associated with the features described above, but PC-2 has several additional features that are not typically seen in PC-1. For example, most people with PC-2 develop widespread cysts called steatocystomas during puberty. People with PC-2 are also more likely to have hair that is twisted or kinked, brittle, and coarse. Additionally, some babies with PC-2 have prenatal or natal teeth, which are teeth that are present at birth or in early infancy.

How common is pachyonychia congenita?

Although the prevalence of pachyonychia congenita is unknown, it appears to be extremely rare. There are probably several thousand people worldwide with this disorder.

What genes are related to pachyonychia congenita?

Mutations in the KRT6A, KRT6B, KRT16, and KRT17 genes can cause pachyonychia congenita. These genes provide instructions for making proteins called keratins. Keratins are tough, fibrous proteins that provide strength and resiliency to the tissues that make up the skin, hair, and nails.

Mutations in the KRT6A or KRT16 gene result in PC-1, while mutations in KRT6B or KRT17 result in PC-2. Mutations in any of these genes alter the structure of a keratin protein, which prevents keratins from forming strong, stable networks within cells. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Defective keratins also disrupt the growth and function of cells in the hair follicles and nails, which leads to the other features of pachyonychia congenita. Read more about the KRT6A, KRT6B, KRT16, and KRT17 genes.

How do people inherit pachyonychia congenita?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. It is estimated that in half of all cases, an affected person inherits the mutation from one affected parent. The other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Hereditary Palmoplantar Keratoderma: A Rare Case ReportPachyonychia Congenita

Elghblawi Ebtisam Posted: 05/18/2010; Dermatology Nursing. 2009;21(6):351-353. 2009 Jannetti Publications, Inc.

Abstract and Introduction

Abstract

The "Clinical Snapshot" series provides a concise examination of a clinical presentation including history, treatment, patient education, and nursing measures. Using the format here, you are invited to submit your "Clinical Snapshot" to Dermatology Nursing.
Introduction

Pachyonychia congenita (PC) is a rare form of hereditary palmoplantar keratoderma (PPK) (Smith et al., 2001) and is a genetic disorder of keratinization that affects the nails, skin (particularly palms and soles), oral mucosa and laryngeal mucosa, teeth, and hair (Karen & Schaffer, 2007; Liao et al., 2007; Smith et al., 2001; Strober, 2003). PC is in one of the four genes encoding keratin 6a, 6b, 16, and 17 (McGowan et al., 2002; Smith et al., 2001). These genes are responsible for the process by which keratin is formed and deposited in the outer most layer of the skin. In the dermatologic literature, PC is better known as Jadassohn-Lewandowsky syndrome (Karen & Schaffer, 2007; Strober, 2003). PC may be hereditary (inherited from a parent who has PC; autosomal dominant) or may be spontaneous or sporadic (a mutation occurs during conception when no parent or other family member has PC) (Dahl, Daoud, & Su, 1995; Mouaci-Midoun, Cambiaghi, & Abimelec, 1996; Stratigos & Baden, 2001; Vaccaro, Guarneri, Barbuzza, & Guarneri, 2008). Few cases of autosomal recessive pachyonychia congenita have been reported. Some cases might appear in adult life (pachyonychia congenital tarda).Pachyonychia means thick nails, from the Greek words, pachys, thick, and onyx, nail. There are

two subtypes of PC (see Table 1), but marks of PC may include (see Table 2): thickened nails (hypertrophic nail dystrophy), painful blisters and calluses on hands and feet (focal palmoplantar hyperkeratosis), follicular hyperkeratosis, and oral leukokeratosis (white film on tongue, cheeks, and sometimes larynx). Multiple cysts of various types (including steatocystoma and pilosebaceous cysts) develop during puberty which are useful features distinguishing PC2 from PC1. Other features include sores at the corner of the mouth (angular chelitis), teeth at or before birth (natal or pre-natal teeth), and hoarse voice (laryngeal involvement) (Cardinali, Torchia, Caproni, Petrini, & Fabbri, 2004; El-Matary & Barnard, 2004; Feinstein, Friedman, & Schewach-Millet, 1988; Kansky, 2007; Karen & Schaffer, 2007; Liao et al., 2007; Mahajan, Pall, Garg, & Gupta, 2003; Stratigos & Baden, 2001; Strober, 2003; Terrinoni et al., 2001).
Table 1. Types of Pachyonychia Congenital

Pachyonychia Congenita Type 1, Jadassohn-Lewandowsky Type

Main features: Nail changes, palmoplantar hyperkeratosis, follicular hyperkeratosis (thickened horny plugs) on the face and extensor surfaces of the limbs, oral leukokeratosis (whitish areas within the mouth) Mutation occurs in keratin K6a or K16

Pachyonychia Congenita Type 2, Jackson-Lawler Type

Main features: Natal teeth, steatocystoma multiplex, epidermoid cysts, hair abnormalities Mutation occurs in keratin K6b or K17

Table 2. Main Clinical Features of Pachyonychia Congenital

Painful thicken palms and soles causing difficult walking Palms and soles Hyperhidrosis Friction blisters Nails Hair Eyes Larynx Abnormal, thicken, brownish 20 nails apparent early in life Alopecia or coarse hair Corneal opacity, cataracts Hoarseness of voice

The first case was documented in 1904 by Muller (Bondeson, 1993), followed by Wilson, Jadassohn, and Lewandowsky consecutively 1905 and 1906. In 1951, Jackson and Lawler described another new case (Bondeson, 1993). PC has no sex or ethnic group predilection. On the other hand, a search of the older

literature discloses a number of older cases of definite pachyonychia congenita, some of them from the 17th and 18th centuries. In 1716, Musaeus described a case of the pachyonychia congenita syndrome in some detail (Bondeson, 1993).

Case Report
A 10-year-old Caucasian girl presented with history of patchy thicken palms and soles, associated with tubular thickened, yellowish-brown discoloration nails that were projecting upward at the free edge to form a tapering curved roof over a mass of sublingual keratotic debris, which resembled sublingual hyperkeratosis or pincer nails (see Figure 1). These changes affected all 20 nails, and began developing early in life. Moreover she developed painful blisters and callouses on her feet which made walking impossible and unbearable. These changes were associated with hyperhidrosis, which was foul smelling. She also had alopecia of scalp, eyebrows, and eyelashes (see Figure 2). No other family members were affected.

Figure 1. Clinical examination revealed hyperkeratotic nails of both fingers and toes, together with patchy thickening of palms and soles.

Figure 2. Total loss of scalp hair, eyebrows, and eyelashes. Examination revealed that the patient was slightly annoyed with a patchy painful thicken skin on her palms, dorsa of hand, and soles. She had total loss of scalp hair, eyebrows, and eyelashes. Cultures of nails were negative for fungal infections. A diagnosis of PC was made based on clinical findings, especially the characteristic of nail morphology. The eyes were normal. Mucocutaneous examination revealed no presence of leukokeratosis. The remainder of her examination was unremarkable. Results for complete blood count, chemistries, lipid panel, urinalysis, and liver function were normal apart from a slight rise in erythrocyte sedimentation rate (30 mm/hr). Treatment included emollients, such as urea cream 10%; keratolytics; salicylic acid ointment 20% with occlusive dressings to soften the thickened nail plate; and oral retinoids (decutan capsules 20 mg which contains the active substance isotretinoin). The patient showed dramatic improvement to some extent on this treatment.

Discussion
This young girl had the illness since birth; although her parents were both relatives (consanguinity marriage), neither of them has the disease. She was the only family member known to be affected with PC, suggesting that the condition could be attributed to a de novo mutation or the recessive form of PC. As she was only 10 years old, this would not indicate the type of PC because steatocystoma develops with or after puberty. (Steatocytoma is a form of pilosebaceous tumor consisting of dermal cysts and

nodules. It presents as yellowish nodules over the anterior neck, chest, trunk, axillary region, and upper abdomen.) Few cases (approximately 250) of PC are reported in the medical literature due to the rarity of the disease. There were no previous cases reported from Libya. The author claims this case to be the first reported case of PC from Libya. Pachyonychia congenita may present more within families of consanguine marriage where a parent is the carrier of a defective gene, and the full presentation appears later in the offspring. Sometimes genetic mutation may occur where a single case emerges in a family without a prior known history. Successful targeted therapies are still currently lacking and only directed at the explicit manifestation per se; therefore, genetic counseling is advised to avoid such conditions.

Recommendations
Genetic counseling and molecular genetic studies are recommended to detect mutations in the affected keratin genes. Family screening for genetic disease and advice about consanguinity marriage and its sequale are also very important.
References

Bondeson J. (1993). Pachyonychia congenita. A historical note. American Journal of Dermatopathology, 15(6), 594599. Cardinali, C., Torchia, D., Caproni, M., Petrini, N., & Fabbri, P. (2004). Case study: Pachyonychia congenita: A mixed type II-type IV presentation. Skinmed, 3(4), 233235. Dahl, P.R., Daoud, M.S., & Su, W.P. (1995). Jadassohn-Lewandowski syndrome (pachyonychia congenita). Seminars in Dermatology, 14(2), 129134. El-Matary, W.M., & Barnard, I. (2004). Images in neonatal medicine. Pachyonychia congenita. Archives of Disease in Childhood, Fetal and Neonatal Edition, 89(5), F467. Feinstein, A., Friedman, J., & Schewach-Millet, M. (1988). Pachyonychia congenita. Journal of the American Academy of Dermatology, 19(4), 705711. Kansky, A. (2007). Pachyonychia congenita. Retrieved December 13, 2008, from http://emedicine.medscape.com/article/1106169-overview Karen, J.K., & Schaffer, J.V. (2007). Pachyonychia congenita associated with median rhomboid glossitis. Dermatology Online Journal, 13(1), 21. Liao, H., Sayers, J.M., Wilson, N.J., Irvine, A.D., Mellerio, J.E., Baselga, E., et al. (2007). A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. Journal of Dermatological Science, 48(3), 199205. Mahajan, B.B., Pall, A., Garg, G., & Gupta, R.R. (2003). Pachyonychia congenita-like nail changes treated successfully with a combination of vitamins A and E: A case report. Indian Journal of Dermatology, Venereology and Leprology, 69(5), 338339. McGowan, K.M., Tong, X., Colucci-Guyon, E., Langa, F., Babinet, C., & Coulombe, P.A. (2002). Keratin 17 null mice exhibit age- and strain-dependent alopecia.Genes & Development, 16(11), 14121422. Mouaci-Midoun, N., Cambiaghi, S., & Abimelec, P. (1996). Pachyonychia congenital tarda. Journal of the American Academy of Dermatology, 35(2 Pt 2), 334335. Smith, F.J., Coleman, C.M., Bayoumy, N.M., Tenconi, R., Nelson, J., David, A., et al. (2001). Novel keratin 17 mutations in pachyonychia congenita type 2. Journal of Investigative Dermatology, 116(5), 806808.

Stratigos, A.J., & Baden, H.P. (2001). Unraveling the molecular mechanisms of hair and nail genodermatoses. Archives of Dermatology, 137(11), 14651471. Strober, B.E. (2003). Pachyonychia congenita, type II. Dermatology Online Journal, 9(4), 12. Terrinoni, A., Smith, F.J., Didona, B., Canzona, F., Paradisi, M., Huber, M., et al. (2001). Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita. Journal of Investigative Dermatology, 117(6), 13911396. Vaccaro, M., Guarneri, F., Barbuzza, O., & Guarneri, C. (2008). Pachyonychia congenita tarda affecting only the nails. Dermatology Online Journal, 14(2), 12.

Dermatology Nursing. 2009;21(6):351-353. 2009 Jannetti Publications, Inc.

What Is Pachyonychia Congenita?

PC is an ultra rare genetic skin disorder caused by a single mutation in one of at least four keratin genes including K6a, K6b, K16 or K17. PC may be hereditary (inherited from a parent who has PC) or may be spontaneous (a mutation occuring when no parent or other family member has PC). Features of PC may include: 1 Painful blisters and calluses on hands and feet (focal palmar
and plantar hyperkeratosis) 2 Thickened Nails (hypertrophic nail dystrophy or pachy-onychia)

3 Follicular hyperkeratosis (bumps around hairs at friction sites such as waist,

hips, knees, elbows)

4 Leukokeratosis of the oral mucosa (white film on tongue, cheeks and

sometimes larynx)

5 Cysts of various types (including steatocystoma and pilosebaceous cysts) Other features include sores at the corner of the mouth (angular chelitis); teeth at or before birth (natal or pre-natal teeth); hoarse voice (laryngeal involvement). Note: Some with PC often suffer intense pain near
the jaw or ears lasting 15-25 seconds when beginning to eat. This may be connected to salivary glands rather than to ears. More research is needed on this.

Pachyonychia congenita
What is pachyonychia congenita? Pachyonychia congenita is a rare, inherited disorder of keratinisation. This is the process by which keratin is formed and deposited in the outer most layer of the skin. It occurs due to mutation in the genes encoding keratin 6a, 6b, 16 and 17.

How is it inherited?

Pachyonychia congenita is most often autosomal dominantly inherited. That means the defective gene comes from one parent. An affected person has a 50% chance of passing on the disease to his or her offspring at each pregnancy. A few cases of autosomal recessive pachyonychia congenita have also been reported, in which a family history may not be known as the abnormal gene is inherited from both parents. In this case, on average, one in every four of the offspring are affected. Sporadic cases may also arise, due to mutations during conception.

What are the features of pachyonychia congenita?

Pachyonychia congenita affects the skin (especially palms and soles), nails, hair and mucous membranes.

Pachyonychia congenita

Clinical feature of pachyonychia congenita Palms and soles

Painful thickened palms and soles (palmoplantar hyperkeratosis or keratoderma), resulting in Hyperhidrosis (excessive sweating) Blisters precipitated by friction and warm weather Abnormal nails apparent early in life Nails are thickened with brownish discolouration All finger nails are commonly involved; toe nails to a lesser degree Coarse unruly hair Sometimes loss of hair (alopecia)

Nails

Hair

Eyes

Corneal opacities Cataracts Hoarseness may occur Rarely, respiratory obstruction and death in infancy

Larynx

Classification of pachyonychia congenita

Pachyonychia congenita is classified into at least two types according to the clinical features,. Particular features may be more prominent in some patients than in others. Pachyonychia congenita type 1 Type 1 (MIM# 167200) is also known as the Jadassohn-Lewandowsky type of pachyonychia congenita. Features are:

Nail changes Palmoplantar hyperkeratosis Follicular hyperkeratosis (thickened horny plugs) on the face & extensor surfaces of the limbs Oral leukokeratosis (whitish areas inside the mouth)

Pachyonychia congenita type 2 Type 2 (MIM# 167201) or the Jackson-Lawler type of pachyonychia congenita includes the features of type 1 plus:

Natal (birth) teeth Steatocystoma multiplex Epidermoid cysts Hair abnormalities

How is Pachyonychia congenita diagnosed?

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.

Treatment

Unfortunately there is no cure for pachyonychia congenita. The effectiveness of treatment depends on the severity of the specific problem. Treatment might include:

Emollients Keratolytics e.g. salicylic acid ointment Mechanical debridement Oral retinoids e.g. acitretin