Nail the Genetic Disorder

1. The patient has a long-standing pruritic rash. Flat, slightly elevated, greasy brown papules are scattered on the chest, abdomen, and ­upper back, with mild surrounding erythema. The fingernails are deformed, with longitudinal red streaks and ridges and v-shaped notching of the free margin.
Reprinted with permission from Cutis. 2003;72:124-126.

Diagnosis: Darier disease (DD) or Darier-White disease is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.^1,2 This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.³ Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.³ Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).² DD is not contagious.²

1. Creamer D, Barker J, Kerdel FA. Papular and papulosquamous dermatoses. In: Acute Adult Dermatology: Diagnosis and Management (A Colour Handbook). London, UK: Manson Publishing Ltd; 2011:48.

2. Kelly EB. Darier disease (DAR). In: Encyclopedia of Human Genetics and Disease. Santa Barbara, CA: ABC-CLIO; 2013:186-187.

3. Ringpfeil F. Dermatologic disorders. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:101.

For more information on this case, see “Man, 45, With Greasy Rash and Deformed Nails.” Clin Rev. 2014;24(1):38,40-41

For the next photograph, proceed to the next page >>

2. Six months ago, this 36-year-old man’s left fourth finger began to bother him. He’s tried topical antibiotics, colloidal silver solution, and two different oral antibiotics. None have relieved the pain, which is severe enough to interfere with daily activity—particularly his job, which requires extensive computer time.

Diagnosis: “Infection” is only one potential cause of redness, swelling, increased warmth, and localized pain. Classically termed rubor, tumor, calor, and dolor, these are indicators of inflammation, which can occur in many conditions besides “infection.” In the case described, a simple hangnail was incompletely removed, leaving a shard of nail that then dug into the perionychial skin as it grew out. This set into motion a healing process that could not proceed to resolution, because the tissue was re-injured every time the finger struck the computer keyboard. This not only caused the wound to get stuck in a certain phase of healing (angioneogenesis) but also prevented completion of the process.

For more information on this case, see “Red and Swollen Doesn’t Mean “Infection.” Clin Rev. 2014;24(6):W1.

For the next photograph, proceed to the next page >>

3. A 25-year-old man presents with what he describes as a “fungal infection” of the fingernails that he’s had since birth. The nails are uniformly thickened and dystrophic, without significant discoloration. The patient’s palms and soles are hyperkeratotic, and the upper anterior legs are covered by a folliculocentric papular hyperkeratosis reminiscent of a coarse keratosis pilaris.

Diagnosis: Pachyonychia congenita (PC) is a rare condition that represents a mutation of keratin genes and is usually of autosomal dominant inheritance. First described by Muller in 1904, it was eventually categorized into one of two types: type I, MIM 167200, also known as Jadassohn-Lewandowsky, the most common type, and type II, MIM 167210, also known as Jackson-Lawler, with slightly different features. Today, a more common view is that no such divisions exist—only variations of PC that exhibit overlapping features.

For more information on this case, see “A fingernail "infection" present since birth.” Clin Rev. 2013;23(4):W6.

For the next photograph, proceed to the next page >>

4. Usually apparent at birth, this disorder may manifest with abnormal or missing nails. Characteristic nail changes include triangular lunulae and, most prominently on the thumb and index fingers, hypoplasia. Also apparent are orthopedic changes (particularly affecting the knees and elbows), renal disease, and glaucoma.

Reprinted with permission from Cutis. 2000;66:71, 75-76.

Diagnosis: The osteo-onychodysplasia, or nail-patella syndrome, is an autosomal dominant disorder. Studies have linked the syndrome to chromosome 9q34 and identified point mutations in the LMX1B gene.⁴ Other kindreds have been linked to chromosome 17q21-22.⁵ Prenatal diagnosis is possible, including noninvasive prenatal diagnosis using ultrasonography. Because of the risk for glaucoma, all family members should be screened by an ophthalmologist.⁶

4. Seri M, Melchionda S, Dreyer S, et al. Identification of LMX1B gene point mutations in Italian patients affected with nail-patella syndrome. Int J Mol Med. 1999;4:285-290.

5. Mangino M, Sanchez O, Torrente I, et al. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21-22. Am J Hum Genetics. 1999;65:441-447.

6. Lichter PR, Richards JE, Downs CA, et al. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124:506-515.

For more information on this case, see “What Is Your Diagnosis? Nail-Patella Syndrome.” Cutis. 2000;66:71, 75-76.

1. The patient has a long-standing pruritic rash. Flat, slightly elevated, greasy brown papules are scattered on the chest, abdomen, and ­upper back, with mild surrounding erythema. The fingernails are deformed, with longitudinal red streaks and ridges and v-shaped notching of the free margin.
Reprinted with permission from Cutis. 2003;72:124-126.

Diagnosis: Darier disease (DD) or Darier-White disease is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.^1,2 This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.³ Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.³ Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).² DD is not contagious.²

1. Creamer D, Barker J, Kerdel FA. Papular and papulosquamous dermatoses. In: Acute Adult Dermatology: Diagnosis and Management (A Colour Handbook). London, UK: Manson Publishing Ltd; 2011:48.

2. Kelly EB. Darier disease (DAR). In: Encyclopedia of Human Genetics and Disease. Santa Barbara, CA: ABC-CLIO; 2013:186-187.

3. Ringpfeil F. Dermatologic disorders. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:101.

For more information on this case, see “Man, 45, With Greasy Rash and Deformed Nails.” Clin Rev. 2014;24(1):38,40-41

For the next photograph, proceed to the next page >>

2. Six months ago, this 36-year-old man’s left fourth finger began to bother him. He’s tried topical antibiotics, colloidal silver solution, and two different oral antibiotics. None have relieved the pain, which is severe enough to interfere with daily activity—particularly his job, which requires extensive computer time.

Diagnosis: “Infection” is only one potential cause of redness, swelling, increased warmth, and localized pain. Classically termed rubor, tumor, calor, and dolor, these are indicators of inflammation, which can occur in many conditions besides “infection.” In the case described, a simple hangnail was incompletely removed, leaving a shard of nail that then dug into the perionychial skin as it grew out. This set into motion a healing process that could not proceed to resolution, because the tissue was re-injured every time the finger struck the computer keyboard. This not only caused the wound to get stuck in a certain phase of healing (angioneogenesis) but also prevented completion of the process.

For more information on this case, see “Red and Swollen Doesn’t Mean “Infection.” Clin Rev. 2014;24(6):W1.

For the next photograph, proceed to the next page >>

3. A 25-year-old man presents with what he describes as a “fungal infection” of the fingernails that he’s had since birth. The nails are uniformly thickened and dystrophic, without significant discoloration. The patient’s palms and soles are hyperkeratotic, and the upper anterior legs are covered by a folliculocentric papular hyperkeratosis reminiscent of a coarse keratosis pilaris.

Diagnosis: Pachyonychia congenita (PC) is a rare condition that represents a mutation of keratin genes and is usually of autosomal dominant inheritance. First described by Muller in 1904, it was eventually categorized into one of two types: type I, MIM 167200, also known as Jadassohn-Lewandowsky, the most common type, and type II, MIM 167210, also known as Jackson-Lawler, with slightly different features. Today, a more common view is that no such divisions exist—only variations of PC that exhibit overlapping features.

For more information on this case, see “A fingernail "infection" present since birth.” Clin Rev. 2013;23(4):W6.

For the next photograph, proceed to the next page >>

4. Usually apparent at birth, this disorder may manifest with abnormal or missing nails. Characteristic nail changes include triangular lunulae and, most prominently on the thumb and index fingers, hypoplasia. Also apparent are orthopedic changes (particularly affecting the knees and elbows), renal disease, and glaucoma.

Reprinted with permission from Cutis. 2000;66:71, 75-76.

Diagnosis: The osteo-onychodysplasia, or nail-patella syndrome, is an autosomal dominant disorder. Studies have linked the syndrome to chromosome 9q34 and identified point mutations in the LMX1B gene.⁴ Other kindreds have been linked to chromosome 17q21-22.⁵ Prenatal diagnosis is possible, including noninvasive prenatal diagnosis using ultrasonography. Because of the risk for glaucoma, all family members should be screened by an ophthalmologist.⁶

4. Seri M, Melchionda S, Dreyer S, et al. Identification of LMX1B gene point mutations in Italian patients affected with nail-patella syndrome. Int J Mol Med. 1999;4:285-290.

5. Mangino M, Sanchez O, Torrente I, et al. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21-22. Am J Hum Genetics. 1999;65:441-447.

6. Lichter PR, Richards JE, Downs CA, et al. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124:506-515.

For more information on this case, see “What Is Your Diagnosis? Nail-Patella Syndrome.” Cutis. 2000;66:71, 75-76.

1. The patient has a long-standing pruritic rash. Flat, slightly elevated, greasy brown papules are scattered on the chest, abdomen, and ­upper back, with mild surrounding erythema. The fingernails are deformed, with longitudinal red streaks and ridges and v-shaped notching of the free margin.
Reprinted with permission from Cutis. 2003;72:124-126.

Diagnosis: Darier disease (DD) or Darier-White disease is a rare genetic skin disorder caused by mutations of the ATP2A2 gene, located on the long arm of chromosome 12 at position 24,11.^1,2 This genetic mutation is inherited as an autosomal dominant trait with complete penetrance. DD affects men and women equally, with progressive skin signs of interfamilial and intrafamilial variability.³ Skin manifestations occur from late childhood to early adulthood and are typical during adolescence.³ Acute flare-ups can be triggered by heat, perspiration, sunlight, ultraviolet B exposure, stress, or certain medications (in particular, lithium).² DD is not contagious.²

1. Creamer D, Barker J, Kerdel FA. Papular and papulosquamous dermatoses. In: Acute Adult Dermatology: Diagnosis and Management (A Colour Handbook). London, UK: Manson Publishing Ltd; 2011:48.

2. Kelly EB. Darier disease (DAR). In: Encyclopedia of Human Genetics and Disease. Santa Barbara, CA: ABC-CLIO; 2013:186-187.

3. Ringpfeil F. Dermatologic disorders. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:101.

For more information on this case, see “Man, 45, With Greasy Rash and Deformed Nails.” Clin Rev. 2014;24(1):38,40-41

For the next photograph, proceed to the next page >>

2. Six months ago, this 36-year-old man’s left fourth finger began to bother him. He’s tried topical antibiotics, colloidal silver solution, and two different oral antibiotics. None have relieved the pain, which is severe enough to interfere with daily activity—particularly his job, which requires extensive computer time.

Diagnosis: “Infection” is only one potential cause of redness, swelling, increased warmth, and localized pain. Classically termed rubor, tumor, calor, and dolor, these are indicators of inflammation, which can occur in many conditions besides “infection.” In the case described, a simple hangnail was incompletely removed, leaving a shard of nail that then dug into the perionychial skin as it grew out. This set into motion a healing process that could not proceed to resolution, because the tissue was re-injured every time the finger struck the computer keyboard. This not only caused the wound to get stuck in a certain phase of healing (angioneogenesis) but also prevented completion of the process.

For more information on this case, see “Red and Swollen Doesn’t Mean “Infection.” Clin Rev. 2014;24(6):W1.

For the next photograph, proceed to the next page >>

3. A 25-year-old man presents with what he describes as a “fungal infection” of the fingernails that he’s had since birth. The nails are uniformly thickened and dystrophic, without significant discoloration. The patient’s palms and soles are hyperkeratotic, and the upper anterior legs are covered by a folliculocentric papular hyperkeratosis reminiscent of a coarse keratosis pilaris.

Diagnosis: Pachyonychia congenita (PC) is a rare condition that represents a mutation of keratin genes and is usually of autosomal dominant inheritance. First described by Muller in 1904, it was eventually categorized into one of two types: type I, MIM 167200, also known as Jadassohn-Lewandowsky, the most common type, and type II, MIM 167210, also known as Jackson-Lawler, with slightly different features. Today, a more common view is that no such divisions exist—only variations of PC that exhibit overlapping features.

For more information on this case, see “A fingernail "infection" present since birth.” Clin Rev. 2013;23(4):W6.

For the next photograph, proceed to the next page >>

4. Usually apparent at birth, this disorder may manifest with abnormal or missing nails. Characteristic nail changes include triangular lunulae and, most prominently on the thumb and index fingers, hypoplasia. Also apparent are orthopedic changes (particularly affecting the knees and elbows), renal disease, and glaucoma.

Reprinted with permission from Cutis. 2000;66:71, 75-76.

Diagnosis: The osteo-onychodysplasia, or nail-patella syndrome, is an autosomal dominant disorder. Studies have linked the syndrome to chromosome 9q34 and identified point mutations in the LMX1B gene.⁴ Other kindreds have been linked to chromosome 17q21-22.⁵ Prenatal diagnosis is possible, including noninvasive prenatal diagnosis using ultrasonography. Because of the risk for glaucoma, all family members should be screened by an ophthalmologist.⁶

4. Seri M, Melchionda S, Dreyer S, et al. Identification of LMX1B gene point mutations in Italian patients affected with nail-patella syndrome. Int J Mol Med. 1999;4:285-290.

5. Mangino M, Sanchez O, Torrente I, et al. Localization of a gene for familial patella aplasia-hypoplasia (PTLAH) to chromosome 17q21-22. Am J Hum Genetics. 1999;65:441-447.

6. Lichter PR, Richards JE, Downs CA, et al. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124:506-515.

For more information on this case, see “What Is Your Diagnosis? Nail-Patella Syndrome.” Cutis. 2000;66:71, 75-76.