PubMed Health⌕ Search

Biomedical subjects

Rudolf Happle

Publications and source records attributed to Rudolf Happle.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cutis tricolor parvimaculata: a distinct neurocutaneous syndrome?

An 11-year-old girl had multiple, disseminated, rather small café-au-lait macules and hypochromic spots involving the neck, the trunk and the legs. In part, the two types of macules showed a spatial proximity, suggesting didymosis (twin spotting). The term cutis tricolor has been proposed to describe congenital paired hyperchromic and hypochromic macules on a background of intermediate skin. Because the spots present in this case were much smaller than those described in previous cases of cutis tricolor, we here propose the distinguishing term 'cutis tricolor parvimaculata'. The underlying gene locus may be a hot spot for postzygotic recombinations, giving rise to multiple twin spots. Moreover, the girl had developed seizures from the age of 10 years, and a large oligodendroglioma involving the left frontal lobe was found. A causal relationship between the cutaneous phenotype and the cerebral tumor is unproven but likely. The skin lesions were reminiscent of a disorder described by Westerhof et al. in 1978 under the term 'hereditary congenital hypopigmented and hyperpigmented macules'. So far, however, it is not clear whether cutis tricolor parvimaculata is identical with or different from this disorder.

Brain Neoplasms↗
PubMed2004

Multiple familial trichoepithelioma caused by mutations in the cylindromatosis tumor suppressor gene.

The recessive oncogene cylindromatosis (CYLD) mapping on 16q12-q13 is generally implicated in familial cylindromatosis, whereas a gene region for multiple familial trichoepithelioma has been assigned to 9p21. Markers from both chromosome intervals were subjected to linkage analysis in a large family with multiple hereditary trichoepithelioma (TE) from Algeria. Linkage to 9p21 was excluded, whereas CYLD remained as a candidate. Mutation analysis identified a single bp germ-line deletion expected to result in truncation or absence of the encoded protein, which segregated with the multiple TE phenotype. In individual tumors, loss of heterozygosity at 16q or a somatic point mutation in the CYLD gene was detected. Hence, mutations of the tumor suppressor gene CYLD at 16q12-q13 may give rise to familial TE indistinguishable from the phenotype assigned to 9p21.

Adult↗
PubMed2004

Unilateral linear hyperpigmentation of the skin with ipsilateral sectorial hyperpigmentation of the retina.

A 32-year-old Caucasian man had a mosaic hyperpigmentation on his left arm, arranged in a pattern following the lines of Blaschko. In addition, a mosaic hyperpigmentation was noted in his left eye, in the form of grouped congenital hypertrophy of the retinal pigment epithelium (CHRPE). Such "bear tracks" are segmentally oriented, well-demarcated, flat, hyperpigmented lesions originating with small dots at the optic disk and expanding towards the periphery. We hypothesize that these mosaic pigmentary lesions involving the skin and the eye on the same side of the body may have originated from an early postzygotic mutation and thus may be etiologically related.

Adult↗
PubMed2004

Melorheostosis may originate as a type 2 segmental manifestation of osteopoikilosis.

Melorheostosis is a non-hereditary disorder involving the bones in a segmental pattern, whereas osteopoikilosis is a rather mild disseminated bone disorder inherited as an autosomal dominant trait. Interestingly, melorheostosis and osteopoikilosis may sometimes occur together. In analogy to various autosomal dominant skin disorders for which a type 2 segmental manifestation has been postulated, melorheostosis may be best explained in such cases as a type 2 segmental osteopoikilosis, resulting from early loss of the corresponding wild type allele at the gene locus of this autosomal dominant bone disorder.

Bone and Bones↗
PubMed2004

Kerinokeratosis papulosa with a type 2 segmental manifestation.

Kerinokeratosis papulosa is a synonym for "waxy keratoses of childhood" (Greek kerinos = waxy). Affected children show multiple disseminated shiny papules involving the entire skin, with a preponderance on the trunk, the upper arms, and the thighs. We describe an additional case supporting the notion that this is a distinctive disorder of keratinization. In this case, the disorder was superimposed by a linear area of excessive involvement affecting the left arm in the form of an epidermal nevus with a shiny, waxy appearance. This linear lesion may be best explained as a type 2 segmental manifestation of the disorder, which would imply that kerinokeratosis papulosa is inherited as an autosomal-dominant trait.

Child↗
PubMed2004

CHILD syndrome avant la lettre.

The CHILD syndrome is an acronymic designation for congenital hemidysplasia with ichthyosiform nevus and limb defects. This X-linked dominant, male-lethal trait is caused by mutations in the gene NSDHL that is localized at Xq28 and involved in cholesterol metabolism. The CHILD nevus that constitutes a hallmark of this multisystem birth defect usually shows a striking lateralization pattern. Until now, a report of Zellweger and Uehlinger from 1948 was believed to represent the first published case of CHILD syndrome. However, we have now found an earlier report published in 1903 by Otto Sachs. An 8-year-old girl had a "xanthoma-like nevus" involving the right axillary region and a congenital muscular weakness of the right upper arm. Sachs described the clinical and histopathological features of CHILD nevus comprehensively, including the characteristic changes of verruciform xanthoma that can be taken within the group of epidermal nevi as a pathognomonic feature of CHILD nevus. This report is the earliest description of CHILD syndrome known so far. Moreover, Sachs presented in this article a comprehensive description of verruciform xanthoma, thus anticipating Shafer's "first report" of this histopathological phenomenon (1971) by almost 70 years.

Axilla↗
PubMed2004

[Alopecia areata in animal models--new insights into pathogenesis and treatment of a T cell-mediated autoimmune disorder].

Alopecia areata is a common disease, but for ethical reasons it seems difficult to perform large-scale studies to elucidate the pathogenesis and to develop new therapeutic approaches in man. It is therefore helpful to develop appropriate animal models. The Dundee experimental bald rat (DEBR) and the C3H/HeJ mouse are well-established animal models for alopecia areata and can be used for the study of genetic aspects, pathogenesis and therapy of the disease. In C3H/HeJ mice alopecia areata can be experimentally induced by grafting lesional skin from an affected mouse to a histocompatible recipient which offers the possibility to study the influence of various factors on the development of the disease. Studies on the C3H/HeJ mouse and the DEBR have corroborated the concept that alopecia areata is a T-cell mediated autoimmune disease and various steps and aspects of the pathogenesis have been elucidated. Based on this knowledge new therapeutic options may be developed such as inhibition of lymphocyte-homing by an anti-CD44v10 antibody, or inhibition of costimulation by monoclonal antibodies. Therapeutic studies in the C3H/HeJ mouse and the DEBR suggest that alopecia areata can be treated by topical tacrolimus but treatment in humans may only be successful after development of an improved vehicle that facilitates penetration of tacrolimus down to the hair bulb. Current investigations in mice are designed to elucidate the mechanisms how contact sensitizers act in the treatment of alopecia areata, and this will hopefully lead to the development of more specific approaches based on the beneficial effect of contact sensitizers.

Alopecia Areata↗
PubMed2004

Gustav Schimmelpenning and the syndrome bearing his name.

Gustav Schimmelpenning was born in 1928 in Oldenburg (Germany). From 1971 until 1994 he was head of the Department of Psychiatry at the University of Kiel. In 1957, while training in neurology and psychiatry, he comprehensively described a case of sebaceous nevus involving the head, with ipsilateral ocular lesions including coloboma of the upper lid, increased density of cranial bones, epileptic seizures and mental retardation. He concluded that this combination of anomalies represented a new 'phacomatosis'. Subsequently this phenotype was reported by other authors under many different names, such as 'Schimmelpenning syndrome', 'Feuerstein-Mims syndrome', 'Schimmelpenning-Feuerstein-Mims syndrome', 'epidermal nevus syndrome', 'Solomon syndrome', 'linear sebaceous nevus syndrome', 'organoid nevus phacomatosis', or 'Jadassohn nevus phacomatosis'. As a consequence of this confusing terminology, Schimmelpenning syndrome even has two different OMIM entries (no. 163200 and no. 165630). The term 'Schimmelpenning syndrome' is both historically justified and practically sufficient to distinguish this phenotype from other epidermal nevus syndromes.

Dermatology↗
PubMed2004

Speckled lentiginous nevus syndrome: report of a further case.

A 42-year-old man had a large speckled lentiginous nevus on the left side of his trunk. The involved area was painful when touched and paresthetic. Moreover, the ipsilateral half of his body showed a pronounced hyperhidrosis. This case can be categorized as a typical example of speckled lentiginous nevus syndrome, a recently recognized phenotype characterized by a speckled lentiginous nevus of the papular type and ipsilateral neurological abnormalities in the form of dysesthesia, muscular weakness or hyperhidrosis. Speckled lentiginous nevus syndrome represents a mosaic phenotype. Most likely it originates from loss of heterozygosity occurring in a heterozygous embryo at an early developmental stage.

Adult↗
PubMed2004

Partial unilateral lentiginosis with ipsilateral Lisch nodules and axillary freckling.

A 9-year-old Taiwanese girl had an unusual combination of multiple lentigines clustered on her left face, 3 cafe-au-lait spots on her left arm and ipsilateral axillary freckling. Two Lisch nodules of the iris were recognized in the left eye but none in the right eye, which is why we established a diagnosis of segmental neurofibromatosis 1. No family member had any sign of neurofibromatosis 1. Moreover, the patient had a large speckled lentiginous nevus involving the left side of her trunk, and her father showed a similar skin disorder on his left buttock. These lesions were taken to be unrelated to the patient's segmental neurofibromatosis 1. This case provides further evidence in favor of the concept that partial unilateral lentiginosis represents a mosaic manifestation of type 1 neurofibromatosis.

Axilla↗
PubMed2004

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept.

Hailey-Hailey disease (HHD) is an autosomal dominant trait characterized by erythematous and oozing skin lesions preponderantly involving the body folds. In the present unusual case, however, unilateral segmental areas along the lines of Blaschko showing a rather severe involvement were superimposed on the ordinary symmetrical phenotype. Based on this observation and similar forms of mosaicism as reported in other autosomal dominant skin disorders, we postulated that in such cases, 2 different types of segmental involvement can be distinguished. Accordingly, the linear lesions as noted in the present case would exemplify type 2 segmental HHD. In the heterozygous embryo, loss of heterozygosity occurring at an early developmental stage would have given rise to pronounced linear lesions reflecting homozygosity or hemizygosity for the mutation. By analyzing DNA and RNA derived from blood and skin samples as well as keratinocytes of the index patient with various molecular techniques including RT-PCR, real-time PCR, and microsatellite analysis, we found a consistent loss of the paternal wild-type allele in more severely affected segmental skin regions, confirming this hypothesis for the first time, to our knowledge, at the molecular and cellular level.

Alleles↗