Multiple Pilosebaceous Cysts Research Articles

Pachyonychia congenita type 2, N92S mutation of keratin 17 gene: clinical features, mutation analysis and pathological view

Pachyonychia congenita (PC) type 2 is a rare inherited genetic disease characterized by hypertrophic nail dystrophy, palmoplantar hyperkeratosis and multiple pilosebaceous cysts. In some cases, natal teeth and hair abnormalities may be present. It is caused by mutations in keratin 17 or its expression partner keratin 6b. Here, an N92S (p.Asn92Ser) germline keratin 17 gene mutation in a pachyonychia congenita type 2 female patient is presented. The pedigree includes the 15 members of a family who showed a severe expression of the phenotype for six generations with a similar clinical picture consisting of sebaceous cysts, nail dystrophy, hyperkeratosis, hair abnormalities, natal teeth, hoarseness and hyperhydrosis. In conclusion, we emphasize the importance of diagnosing and managing pachyonychia congenita in childhood for the assistance of affected children and for the development of potential therapies.

Keratin 17 mutation in pachyonychia congenita type 2 patient with early onset steatocystoma multiplex and Hutchinson‐like tooth deformity

Pachyonychia congenita type 2 (PC-2) is an autosomal dominant disorder characterized by hypertrophic nail dystrophy, focal keratoderma, multiple pilosebaceous cysts, and other features of ectodermal dysplasia. It has been demonstrated that PC-2 is caused by mutations in the keratin 17 and keratin 6b genes. In this report, we describe a missense mutation in the keratin 17 gene, M88T, in a Korean patient whose phenotype included early onset steatocystoma multiplex and Hutchinson-like tooth deformities along with other typical features of PC-2 such as hypertrophic nails, natal teeth and follicular hyperkeratosis.

Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts

Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts

Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts

Acquired multiple pilosebaceous cysts on the face having the histopathological features of steatocystoma multiplex and eruptive vellus hair cysts

In vivo alteration of the keratin 17 gene in hair follicles by oligonucleotide-directed gene targeting.

Using intradermal injection of a chimeric RNA-DNA oligonucleotide (RDO) or a single-stranded oligonucleotide (ssODN) into murine skin, we attempted to make a dominant mutation (R94p) in the conserve alpha-helical domain of keratin 17 (K17), the same mutation found in pachyononychia congenichia type 2 (PC-2) patients with phenotypes ranging from twisted hair and multiple pilosebaceous cysts. Both K17A-RDO and -ssODN contained a single base mismatch (CGC to CCC) to alter the normal K17 sequence to cause an amino acid substitution (R94P). The complexes consisting of oligonucleotides and cationic liposomes were injected to C57B1/6 murine skin at 2 and 5 day after birth. Histological examination of skin biopsies at postnatal day 8 from several mice showed consistent twisted hair shafts or broken hair follicles at the sebaceous gland level and occasional rupture of the hair bulb or epidermal cyst-like changes. In the injected area, the number of full anagen hair follicles decrease by 50%. Injection of the control oligonucleotide, identical to K17A-RDO but containing no mismatch to the normal sequence, did not result in any detectable abnormality. The frequency of gene alteration was lower than 3%, according to the restriction fragment length polymorphism (RFLP) analysis of the genomic DNA isolated by dissection of hair follicles from slides. Although intradermal injection of K17A-RDO or K17-ssODN caused a dominant mutation in K17 affecting hair growth and morphology, these phenotypic changes were transient either due to the compensation of K17 by other keratins or the replacement of the mutated cells by normal surrounding cells during hair growth.

Novel Keratin 17 Mutations in Pachyonychia Congenita Type 2

Pachyonychia congenita type 2 is an inherited ectodermal dysplasia characterized by hypertrophic nail dystrophy and multiple pilosebaceous cysts. Focal nonepidermolytic palmoplantar keratoderma, natal teeth, and pili torti may also be present. Epithelial tissues affected in pachyonychia congenita type 2 express the keratin pair K6b/K17. Here, we report three novel heterozygous mutations in the K17 gene (KRT17A) in patients presenting with pachyonychia congenita type 2. These mutations, R94-98del (deletion of the peptide sequence RLASY) and missense mutations R94P and L95Q, are all within the 1A domain hotspot for pathogenic keratin mutations.

Pachyonychia congenita. Keratin gene mutations with pleiotropic effect

Pachyonychia congenita (PC) comprises a heterogeneous group of autosomal dominantly inherited conditions showing characteristic nail thickening and associated signs such as palmoplantar keratoderma, follicular keratoses, and mucosal leukokeratoses. Less frequently epidermal cysts, hairshaft abnormalities, natal teeth and laryngeal involvement may be seen. Phenotypically and genetically two major forms of PC are recognized, pachyonychia congenita Jadassohn-Lewandowsky/PC type I (Medelian inheritance in man-MIM-167200) and pachyonychia congenita Jackson-Lawler/PC type II (MIM 167210). Both conditions show nail deformities, focal palmoplantar keratoderma, and follicular hyperkeratoses. Diagnostically relevant are leukokeratoses of the oral mucosa in patients with PC type I. In contrast individuals affected with PC type II show premature dentition and multiple pilosebaceous cysts predominantly affecting the upper trunk. The latter closely resemble eruptive vellus hair cysts and steatocystoma multiplex. By mutational analysis keratin K6a and K16 gene mutations have been detected in patients with PC type I, and keratin K6b and K17 gene mutations have been shown to be the underlying genetic defect in patients with PC type II.

Missense Mutations in Keratin 17 Cause Either Pachyonychia Congenita Type 2 or a Phenotype Resembling Steatocystoma Multiplex

Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias in which the main phenotypic characteristic is hypertrophic nail dystrophy. In the Jackson-Lawler form (PC-2), pachyonychia is accompanied by multiple pilosebaceous cysts, natal teeth, and hair abnormalities. By direct sequencing of genomic PCR products, we report heterozygous K17 missense mutations in the same conserved protein motif in a further five PC-2 families (K17 N92S in one familial and three sporadic cases; K17 Y98D in one familial case) confirming that mutations in this gene are a common cause of PC-2. We also show heterozygous missense mutations in K17 (N92H and R94H) in two families diagnosed as steatocystoma multiplex. Mild nail defects were observed in some but not all of these patients on clinical re-evaluation of these families. All the K17 mutations reported here were shown to co-segregate with the disease in the pedigrees analyzed and were excluded from 100 unaffected, unrelated chromosomes by restriction enzyme analysis of K17 genomic PCR products. We conclude that phenotypic variation is observed with K17 mutations, as is the case with other keratin disorders.

Multiple pigmented follicular cysts: a subtype of multiple pilosebaceous cysts

Pigmented follicular cyst is a rare disorder which typically presents as a pigmented papule on the head or neck and which, histologically, exhibits terminally differentiated, pigmented hair shafts in an epidermoid cyst. We report a 22-year-old man with the multiple variant of this disorder. Clinically he had numerous brown-blue to flesh-coloured, domed-shaped papules, on the anterior chest and abdomen, of 10 years duration. Histologically, hybrid cysts exhibiting trichilemmal and epidermoid keratinization were seen. The cysts contained numerous pigmented, terminally differentiated hair shafts and, embedded in the wall of one cyst, was a sebaceous gland. The condition of multiple pigmented follicular cysts, is thought to represent a distinct subtype within the spectrum of multiple pilosebaceous cystic disorders.

Multiple pigmented follicular cysts: a subtype of multiple pilosebaceous cysts

Multiple pigmented follicular cysts: a subtype of multiple pilosebaceous cysts

Relationship between steatocystoma multiplex and eruptive vellus hair cysts

Steatocystoma multiplex (SM) and eruptive vellus hair cysts (EVHC) share a clinical resemblance, but have distinctive histologic features. We describe a patient who had both SM and EVHC lesions and discuss the relationship between the two diseases. We believe that SM and EVHC are within the spectrum of the same disease process and could both be termed multiple pilosebaceous cysts.