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Background: The association of Blaschko lines with genetic mosaicism has lead to the concept that this pattern represents the manifestation of genetically abnormal skin tissue contrasting with the genetically normal skin. Various mosaic defects affecting not only the skin but also extracutaneous tissues have lead to the description of different types of epidermal nevus syndromes. We present a further case of an unusual organoid epidermal nevus characterized by depigmented hypertrichosis., Main Observations: We describe a 2-year-old boy with a systematized angora hair nevus being characterized by bands covered with soft white hair arranged along Blaschko's lines, involving the scalp, face, and trunk. A biopsy obtained from a scalp lesion showed mild epidermal acanthosis and increased pigmentation of the basal layer. Trichoscopy the affected scalp hair demonstrated fine light coloured shafts. The boy had slight macrocephaly and body asymmetry, a sacral pit, and koilonychia of the big toes., Conclusions: The angora hair nevus is a peculiar type of organoid epidermal nevus, representing the cutaneous hallmark of a distinctive syndrome, the angora hair nevus syndrome (Schauder syndrome). In cases of epidermal nevi showing hypertrichosis, this unusual entity should be borne in mind for differential diagnosis.

Acanthosis nigricans has been described in several autosomal dominant skeletal dysplasia syndromes due to germline FGFR3 mutations, but rarely specifically in patients with hypochondroplasia. We report a child who presented with extensive acanthosis nigricans, short stature, and radiographic evidence of hypochondroplasia. Genetic analysis revealed a heterozygous K650Q mutation in FGFR3., (© 2010 Wiley Periodicals, Inc.)

Desmosomes are intercellular adhesive junctions and attachment sites for the intermediate filament (IF) cytoskeleton, prominent in tissues subject to high levels of mechanical stress such as the epidermis and heart. The obligate desmosomal constituent, plakoglobin (PG), is involved in coupling transmembrane desmosomal components with IFs. PG also contributes to intercellular adhesion through adherens junctions and has additional signaling roles. To date, two mutations in the gene encoding PG, JUP, have been described, and in both instances, patients harboring pathogenic mutations suffered from arrhythmogenic right ventricular cardiomyopathy with or without skin abnormalities. We describe homozygous nonsense mutation, p.S24X, and homozygous splice site mutation, c.468G>A, in the JUP gene that results in skin fragility, diffuse palmoplantar keratoderma, and woolly hair with no symptoms of cardiomyopathy. We show barely detectable levels of PG immunostaining in skin sections from patients harboring these mutations and show that an alternative AUG codon in p.S24X mRNA translates a 42-amino-acid N-terminal truncation. We conclude that PG is required for correct maintenance of skin integrity, and the absence of heart phenotype in patients suggests that aberrant PG expression does not compromise normal human heart development in children. Our findings provide new insight into the distinct roles that PG has in the epidermis and heart.

Ichthyosis follicularis with atrichia and photophobia (IFAP syndrome) is a rare X-linked, oculocutaneous human disorder. Here, we assign the IFAP locus to the 5.4 Mb region between DXS989 and DXS8019 on Xp22.11-p22.13 and provide evidence that missense mutations exchanging highly conserved amino acids of membrane-bound transcription factor protease, site 2 (MBTPS2) are associated with this phenotype. MBTPS2, a membrane-embedded zinc metalloprotease, activates signaling proteins involved in sterol control of transcription and ER stress response. Wild-type MBTPS2 was able to complement the protease deficiency in Chinese hamster M19 cells as shown by induction of an SRE-regulated reporter gene in transient transfection experiments and by growth of stably transfected cells in media devoid of cholesterol and lipids. These functions were impaired in five mutations as detected in unrelated patients. The degree of diminished activity correlated with clinical severity as noted in male patients. Our findings indicate that the phenotypic expression of IFAP syndrome is quantitatively related to a reduced function of a key cellular regulatory system affecting cholesterol homeostasis and ability to cope with ER stress.

A pronounced linear eruption with ulcerations and calcium extrusion present in a boy with a mild generalized rash clinically consistent with juvenile dermatomyositis or overlap syndrome is reported. Loss of heterozygosity (LOH) is a postzygotic mechanism by which a heterozygous somatic cell may become homozygous or hemizygous at a given gene locus. Such a mechanism can be suspected when a pronounced segmental manifestation of an acquired skin condition with a polygenic background is found to be superimposed on more or less symmetrically distributed nonsegmental lesions of the same disorder. Alternatively, such a segmental manifestation may reflect heterozygosity for a postzygotic mutation involving an additional gene locus. The severe linear lesions in our patient showed a Blaschko-linear arrangement and were superimposed on mild nonsegmental lesions of either amyopathic dermatomyositis or overlap syndrome. Either LOH or a postzygotic mutation at an additional gene locus may explain the pronounced linear involvement., (Copyright 2009 S. Karger AG, Basel.)

An 8-year-old mentally retarded boy had paired segmental areas of hyper- and hypopigmentation on the left side of his body in association with cutis marmorata telangiectatica congenita (CMTC) involving the trunk and the limbs, with the exception of parts of his right arm. At the age of 4 years, an aneurysmatic nodular lesion developed in the angle of his right elbow, and subsequently two similar lesions emerged on his forehead and scalp. Moreover, a dysmorphic facial appearance, scoliosis, genu valgum, talipes planus and increased laxity of joints were noted. The coexistence of paired achromic and melanotic macules in the form of "cutis tricolor" with CMTC can be categorized as an unusual example of phacomatosis pigmentovascularis (PPV). This combination differs from all other types of PPV so far known, which is why we propose the new term "phacomatosis achromico-melano-marmorata". Future clinical research may show whether analogous "simple" twin-spot phenotypes in the form of "phacomatosis melanomarmorata" or "phacomatosis achromicomarmorata" do likewise exist.

Levamisole is an antihelmintic drug that stimulates antibodies formation increasing both T response, and neutrophilic response, and quimiotaxis. It is used in dermatology for the treatment of plane warts, erythema multiforme, aphtous ulcers and, with prednisone, in lichen planus. With prolonged use this drug has been implicated in adverse dermatological reactions as lichenoid eruptions, ulcers and vasculitis. We present a 9-years old girl who developed a cutaneous eruption and a reverse leucoencephalopathy with a short treatment but high doses of the drug.

This is a follow-up report on a boy with phacomatosis pigmentokeratotica. At the age of 10 years he had, in addition to a sebaceous nevus and a speckled lentiginous nevus, multiple lesions of a collagen nevus localized on the chin and in the lumbar area. On the left shoulder, a small telangiectatic spot was present within the area of the speckled lentiginous nevus. Moreover, hemiatrophy of the left-hand side of the body and hyperhidrosis of the left lumbar area were noted. At the age of 16, the lesions of his collagen nevus had considerably enlarged and showed an arrangement along Blaschko lines. Additional pinhead-sized vascular lesions were noted, with preponderance within the area of the speckled lentiginous nevus in the left scapular region and on his left leg. Moreover, the boy had developed severe arterial hypertension since the age of 13. Angiographic examination showed an aortic stenosis that reached from the aortic arch down to the origin of the renal arteries, necessitating a surgical intervention. From this follow-up report we conclude that phacomatosis pigmentokeratotica may be associated with other cutaneous abnormalities such as linear connective tissue nevus of the collagen type and multiple pinhead-sized angioma-like lesions superimposed on the speckled lentiginous nevus. The associated defects of the large vessels may belong to the component of Schimmelpenning syndrome representing one "half" of phacomatosis pigmentokeratotica, rather than being part of the speckled lentiginous syndrome that forms the other "half" of this twin-spot phenotype.

We report a family in which geroderma osteodysplastica affected two male siblings. They showed the characteristic features associated with this syndrome: a prematurely aged face with wrinkly, lax skin, more prominent on the acral regions, associated with joint laxity, osteoporosis, and skeletal abnormalities. The main histologic abnormalities were fragmented elastic fibers that were diminished in number. Although collagen fibers showed changes in their orientation, they were normal in structure and number. We consider the differential diagnosis with other syndromes associated with cutis laxa using clinical, radiologic, and histopathologic criteria.

Desmoplastic hairless hypopigmented nevus (DHHN) is the name Ruiz-Maldonado et al. gave to a new variant of giant congenital melanocytic nevus characterized clinically by a hard ligneous consistency, absence of hair and progressive loss of pigment. Histologically, dermal fibrosis consistent with desmoplasia is a predominant feature. We describe a 6-year-old boy with a hard hairless pigmented congenital nevus involving the lumbosacral area, buttocks, perineum and scrotum. During the first years of life, the nevus showed a progressive reduction in colour, size and consistency. These changes continued until the age of four when a well-demarcated tumour appeared, within the nevus, on the right buttock. Resection of this outgrowth was performed. Histologically, nevus cells of normal appearance between thick collagen bundles were present. Immunostaining revealed S100 +, Vim +, HMB45--results. The nevus has continued to involute to date. An immune response against the melanocytes of the nevus may explain this type of evolution.

Nevus psiloliparus is a distinct type of mesodermal nevus of the scalp characterized by absence or paucity of hair, and presence of an excessive amount of fatty tissue. It is considered a hallmark of encephalocraniocutaneous lipomatosis, a rare disorder comprising a variety of cutaneous, ophthalmologic, and neurologic defects. We report two infants with encephalocraniocutaneous lipomatosis with nevus psiloliparus on the scalp in close association with aplasia cutis congenita. This unusual association may be considered a further example of didymosis, for which we propose the term, didymosis aplasticopsilolipara.

Background: Darier's disease or keratosis follicularis is an autosomal dominant acantholytic disorder that frequently arises as a result of spontaneous mutation. It is either a generalized or localized condition due to a mutation in the SERCA2 12q23-q24,1 resulting in a faulty organization of the tonofilaments. We present two siblings affected with the linear form of this disorder and discuss these cases as an example of the genetic mechanism of loss of heterozygosity., Case Reports: A 7 year-old girl was referred for evaluation of linear lesions present since the first year of age. Examination disclosed red, 1 to 2 mm papules that coalesced to form linear plaques on the left side of the vulvar and perianal areas, and on the left hand and foot. Her older brother had similar lesions in a linear arrangement on the left side of the face neck and homolateral foot. No lesions were found in their parents. Biopsies of both affected children revealed an intraepidermal suprabasal cleft. Dyskeratotic cells were present in the spinous layer, and corps ronds and grains near the granular layer., Discussion: The linear form of Darier's disease could result from genetic mosaicism for this autosomal dominant disorder. As these children have a more pronounced involvement than the usual Darier's disease lesions, disposed in a linear arrangement, they probably represent a type 2 segmental manifestation of the disorder. Likewise, the presence of the same linear disorder in two siblings could be explained by loss of heterozygosity for the Darier's disease gene.

Two siblings with familial cutaneous collagenoma syndrome had the essential clinical features of multiple skin-colored nodules on the trunk and upper arms. On light microscopy, histopathologic findings included excessive accumulation of dense, coarse collagen in the dermis. Elastic tissue stains demonstrated a proportionately diminished number of abnormal elastic fibers intermingled with the collagen bundles. A predominance of densely packed collagen bundles of normal morphology with a marked decrease in abnormal elastic tissue were the major ultrastructural features. The diagnosis was therefore confirmed to be connective tissue nevi of the collagen type. The differential diagnosis of connective tissue nevi disorders is delineated.

The coexistence of linear porokeratosis (LP) and disseminated superficial actinic porokeratosis (DSAP) in a 3-year-old girl with a family history of DSAP is presented. Happle proposed loss of heterozygosity (LOH) to explain the origin of this unusual phenomenon. Homozygosity would explain why lesions in LP are far more pronounced than those of the associated heterozygous DSAP lesions. LOH would also explain the early age of presentation of the linear lesions, the family history of DSAP, and why LP cases are particularly prone to malignant transformation. This case is also important for molecular studies because of the presence of heterozygous and homozygous mutated cells in the same patient and the familial occurrence of the heterozygous form of the disease.

Aplasia cutis congenita is a rare disorder characterized by localized absence of skin at birth. Type V in Frieden's classification, which is associated with fetus papyraceous or placental infarcts, occurs as a large cutaneous defect on the trunk and extremities. The patient we report had a lesion affecting the trunk and extremities symmetrically, with no family history of the disorder or chromosomal abnormalities. In our opinion, despite the absence of fetus papyraceous or placental infarct, this patient's condition can be classified as type V.