Novel TGM5 mutations in acral peeling skin syndrome.

Acral peeling skin syndrome (APSS, MIM #609796) is a rare autosomal recessive disorder characterized by superficial exfoliation and blistering of the volar and dorsal aspects of hands and feet. The level of separation is at the junction of the stratum granulosum and stratum corneum. APSS is caused by mutations in the TGM5 gene encoding transglutaminase-5, which is important for structural integrity of the outermost epidermal layers. The majority of patients originate from Europe and carry a p.(Gly113Cys) mutation in TGM5. In this study, we report both European and non-European families carrying other mutations in the TGM5 gene. In 5 patients, we found 3 novel mutations: c.1001+2_1001+3del, c.1171G>A and c.1498C>T. To confirm their pathogenicity, we performed functional analyses with a transglutaminase activity assay, determined alternative splicing by reverse-transcribed PCR analysis and used databases and in silico prediction tools.

Mutations in the CDSN gene cause peeling skin disease and hypotrichosis simplex of the scalp.

Peeling skin disease is a rare genodermatosis characterized by superficial exfoliation or peeling of the skin. Peeling skin disease is caused by biallelic mutations in CDSN as an autosomal recessive trait. Monoallelic mutations in CDSN have also been described in an autosomal dominant inherited genodermatosis: hypotrichosis simplex of the scalp. This disease is characterized by progressive hair loss of the scalp with onset after early childhood. Clinical data were obtained from a patient with lifelong generalized skin peeling and both his parents. The patient's parents did not suffer from skin peeling, but the mother had a history of thin scalp hair since early childhood. Mutation analysis in the patient showed compound heterozygous mutations in exon 2 of CDSN, a nonsense mutation c.598C>T (p.[Gln200*]), previously associated with hypotrichosis simplex of the scalp, and a frame-shift mutation c.164_167dup (p.[Thr57Profs*6]), previously described in peeling skin disease. The p.(Gln200*) mutation was also found in the mother of the proband. Our study strengthens the previously established link between mutations in CDSN to peeling skin disease and hypotrichosis simplex of the scalp.

[A boy with a chronic swelling of the upper lip]. / Een jongen met chronische zwelling van de bovenlip.

A 14-year-old boy developed a chronic painless swelling of the upper lip. Histology of a skin biopsy showed non-necrotizing tuberculoid granulomas. The diagnosis cheilitis granulomatosa was made.

[A woman with thick nails and a white tongue]. / Een vrouw met verdikte nagels en veel eelt.

A 22-year-old women visited the dermatologist with hypertrophic finger- and toenails, palmoplantar keratoderma and oral leukokeratosis since her childhood. The diagnosis 'pachyonychia congenita type 1' was made. This is a rare dermatosis with an autosomal dominant inheritance pattern. The treatment is symptomatic.

Skin abnormalities in individuals with macrocephaly: Cowden disease from a dermatologist's point of view.

Cowden disease is a rare autosomal dominant disorder characterized by multiple hamartomas and (malignant) tumors affecting major organs including the breast, thyroid, endometrium, brain, skin and mucosa. Diagnostic criteria as formulated by the International Cowden Consortium serve as a guideline to clinically identify patients in which Cowden disease is suspected. However, the spectrum of abnormalities associated with PTEN mutations is very broad, such that the term PTEN hamartoma tumor syndrome (PTHS) is often used. The diagnostic criteria for Cowden disease do not always serve to reliably identify patients who fall within the PTHS spectrum. Therefore, it is important that clinicians are aware of features that should raise the suspicion of such a syndrome. To illustrate this point, we present three patients with clinical features of the PTEN hamartoma tumor syndrome spectrum. These patients have macrocephaly in common. Two of them meet the criteria for Cowden disease; one patient refused mutation analysis, while mutation analysis in the other patient revealed no PTEN mutation. The third patient does not meet the criteria for Cowden disease; however, genetic analysis showed a pathogenic mutation in the PTEN gene. Dermatologists regularly encounter the (muco-)cutaneous abnormalities that can be seen in PTEN hamartoma tumor syndrome. These findings combined with a (family) history of internal malignancy or a macrocephaly should raise the suspicion of PTHS, even in the absence of classical Cowden criteria.

Onycholysis associated with subungual manifestation of barber's hair sinus.

A female hairdresser presented with hair fragments embedded under her fingernails in association with yellow-brownish discoloration and distal detachment of the nails. Based on these findings, we made the diagnosis of subungual barber's hair sinus with onycholysis. To our knowledge, this unique clinical picture has not been reported previously. A detailed medical history revealed several risk factors that might have contributed to the disease. Here, we briefly review what is known about barber's hair sinus, an occupational disease that is usually encountered in male hairdressers and only rarely manifests in women.

Erythema nodosum as an early sign of Crohn's disease.

Erythema nodosum is the most common form of septal panniculitis and the most frequent skin manifestation associated with inflammatory bowel disease. Since the development of erythema nodosum is closely related with a variety of disorders and conditions, it can serve as an important early sign of systemic disease. We report on a 25-year-old woman with Crohn's disease following a long history of recurrent erythema nodosum.