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Poikiloderma with neutropenia (PN), Clericuzio-type is a rare autosomal recessively transmitted genodermatosis caused by biallelic mutations in the USB1 gene and is characterized by early-onset poikiloderma and chronic neutropenia. Nail dystrophy, palmoplantar hyperkeratosis, hypogonadotropic hypogonadism, and recurrent infections can be associated with the disease. Herein, we present a 27-year-old Turkish male patient newly diagnosed as PN, Clericuzio-type after confirmation of a c.531delA (p.His179MetfsX86) homozygous deleterious mutation in exon 5 of the USB1 gene. The presented case highlights the importance of genetic testing for avoiding misdiagnosis based solely on clinical findings, as well as the benefit of a multi-disciplinary diagnostic approach, as he was initially misdiagnosed as Rothmund-Thompson syndrome and subsequently diagnosed as PN, Clericuzio-type at age 27 years.

Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients. This will hopefully allow achieving data clustered on specific mutations relevant to oncological surveillance of the carrier patients. We describe the clinical features of three unreported PN patients and characterize their USB1 pathogenic variants by transcript analysis to get insights into the effect on the overall phenotype and disease evolution. A Turkish boy is homozygous for the c.531delA deletion, a recurrent mutation in Turkey; an adult Italian male is compound heterozygous for two nonsense mutations, c.243G>A and c.541C>T, while an Italian boy is homozygous for the splicing c.683_693+1del variant. The identified mutations have already been reported in PN patients who developed hematologic or skin cancer. Aberrant mRNAs of all four mutated alleles could be identified confirming that transcripts of USB1 main isoform either carrying stop codons or mis-spliced may at least partially escape nonsense-mediated decay. Our study addresses the need of gathering insights on genotype-phenotype correlations in newly described PN patients, by transcript analysis and information on disease evolution of reported patients with the same pathogenic variants.

Xeroderma pigmentosum is a rare autosomal recessive disorder which is caused by germinal mutations responsible for the repair of ultraviolet (UV) radiation-induced DNA lesions. It is characterized by hypersensitivity to UV radiation, poikiloderma, ocular surface disease, and in some patients pronounced sunburn and neurological disease. Patients have a very high risk of developing ocular and skin cancer on exposed body sites. No cure is available for these patients except complete protection from all types of UV radiation.

Poikiloderma with Neutropenia (PN) is inherited genodermatosis which results from a biallelic mutation in the USB1 gene (U Six Biogenesis 1). PN, first described in Navajo Native Americans, is characterized by early onset poikiloderma, pachyonychia, palmo-plantar hyperkeratosis, and permanent neutropenia. This condition results in frequent respiratory tract infections during infancy and childhood. From 2011 to 2013, four cases of PN were diagnosed in Morocco. In this paper, we report the first four cases of PN diagnosed in Morocco, out of three unrelated consanguinous families. We investigated the genetic, immunological, and clinical features of four Moroccan patients with PN from three unrelated consanguinous families. Mean age at onset was 3 months and mean age at diagnosis was 7.5 years. The diagnosis of these PN patients was made based on clinical features and confirmed by molecular analysis for three cases. We identified two undescribed homozygous mutations in the USB1 gene: c.609 + 1G>A in two siblings and c.518 T>G(p.(Leu173Arg)) in the other case. This report confirms the clinical and genetic identity of Poikiloderma with Neutropenia syndrome.

Background Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. Results The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. Conclusions This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients.

Male fertility can be affected by a variety of organs diseases, including the skin. Several genodermatoses affect the skin and several other organs including the male reproductive system, commonly in the form of cryptorchidism and hypogonadism. The most relevant syndromes are associated with dyschromias, such as deSanctis-Cacchione, poikiloderma congenital, LEOPARD, and H syndrome; others with ichthyosis, such as Rud, and trichothiodystrophy; or a group of unrelated genodermatoses, such as ablepharon macrostomia, Coffin-Siris, Gorlin-Goltz, and Werner. Acquired skin diseases may also affect male fertility usually in the form of orchitis or epididymal obstruction or androgen antagonists. These include infections (leprosy and HIV), autoimmune (erythema nodosum leprosum), granulomatous (sarcoidosis, Langerhans cell histiocytosis), nutritional deficiency (zinc), and malignancy. Several therapeutics of skin diseases are notorious for their effects on male fertility, most notably are the cytotoxic drugs (methotrexate), irradiation, and antiandrogens (spironolactone, finasteride). Although the prevalence of these skin diseases is low, the associated male infertility represents a challenge due to the difficulty of its management. Clinical management of the skin diseases should include consideration of their effects not only on the diseases but also on the male reproductive system.

Xeroderma pigmentosum (XP) is a rare disorder of defective UV-radiation induced damage repair that is characterized by photosensitivity with easy skin burning following minimal sun exposure, early freckling and development of lentiginous pigmentation along with other features of poikiloderma and a propensity for developing skin cancer at an early age. In this short review, the clinical, pathological, genetic and molecular aspects of XP are reviewed in the current literature. XP encompasses a spectrum of disease that overlaps with other diseases of DNA repair systems. In addition to cutaneous complications, patients are susceptible to eye conditions, neurodegenerative processes, central nervous system tumors and other tumors as a result of UV radiation exposure and its byproducts. Patients with XP frequently experience a shorter life span due to skin cancer and neurodegenerative sequelae, but aggressive preventative measures to minimize UV radiation exposure and damage can improve the course of disease and prolong life. The disease has served as a model for photoaging and UV radiation-induced cancer and has led to a better understanding of cell processes that prevent development of these disease features in normal individuals.

Background Dermatomyositis is a humoral-mediated inflammatory myopathy with symmetrical proximal muscle weakness and dermatological manifestations such as Gottron’s papules, heliotrope rash, periungual abnormalities, and flagellate erythema. Erythroderma is a severe and potentially life-threatening dermatological condition with diffuse erythema and scaling involving more than 90% of the skin surface area. Poikiloderma vasculare atrophicans refers to mottled hyperpigmentation and hypopigmentation of the skin with in-between telangiectases and areas of atrophy and is considered a variant of mycosis fungoides. Poikilodermatomyositis is the term given to the condition with poikiloderma and inflammatory myopathy. Only a few cases are reported on erythroderma in dermatomyositis and poikilodermatomyositis. Erythrodermal pattern of dermatomyositis transforming into poikilodermatomyositis is a recognized rare manifestation of dermatomyositis and we could find only one case report in the literature. Case presentation A 53-year-old Sri Lankan woman presented with intermittent fever of 5 months’ duration with erythroderma. Later she developed progressive, symmetrical proximal muscle weakness. Following a short course of small dose steroids, erythroderma settled but changed to extensive poikiloderma involving more than 90% of her skin with her face being relatively spared. She had an early heliotrope rash, shawl sign, and Gottron papules. Electromyography and muscle biopsy were supportive of inflammatory myositis and skin biopsy showed evidence of dermatomyositis. Inflammatory markers and muscle enzymes were also elevated. Autoimmune antibodies and myositis-specific autoantibodies were negative. She was started on orally administered prednisolone 1 mg/kg per day with methotrexate 10 mg once a week and had a good response to treatment with resolution of the skin condition and improvement of muscle power. Imaging studies, endoscopies, and tumor markers did not reveal any malignancy. Conclusions This case illustrates a rare presentation of dermatomyositis initially presenting as fever, erythroderma, and proximal muscle weakness and later developing poikiloderma involving more than 90% of the skin. It is important to be aware of this rare presentation to avoid misdiagnosis. With the currently available literature it is not possible to conclude that erythroderma is a bad prognostic factor in dermatomyositis or a predictive factor for a malignancy. Patients have a good response to steroids with a combination of immunosuppressants.

Background Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage, often leading to immunodeficiency, growth retardation and increased risk of malignancy. Case presentation We performed exome sequencing on a girl with a suspected chromosome instability syndrome that manifested as growth retardation, microcephaly, developmental delay, dysmorphic features, poikiloderma, immune deficiency with pancytopenia, and myelodysplasia. She was homozygous for a previously reported splice variant, c.4444 + 3A > G in the POLE1 gene, which encodes the catalytic subunit of DNA polymerase E. Conclusion This is the second family with POLE1-deficency, with the affected individual demonstrating a more severe phenotype than previously described. Electronic supplementary material The online version of this article (doi:10.1186/s12881-015-0177-y) contains supplementary material, which is available to authorized users.

We report on an 18 years old female patient who presented with synechia of the labia. History reveals congenital blistering with acral localization and photosensitivity in childhood. At present, the patient showed wide-spread poikoloderma with reticulate hyperpigmentation, xerosis, proximal synechia between fingers and toes and absence of dermatoglyphics, suggestive for congenital bullous poikiloderma (Kindler syndrome). The diagnosis was confirmed by histology and electron microscopy. Kindler syndrome is a rare, autosomal recessive disorder with synechia of mucosal areas being the presenting symptom.

Rothmund Thomson syndrome (RTS) is a rare autosomal recessive disorder which is primarily diagnosed by clinical manifestations that include poikiloderma, short stature, sparse hair distribution, juvenile cataracts, small hands and feet, bone defects, photosensitivity, hypogonadism, defective dentition, onychodystrophy, and hyperkeratosis. Although a few reports have been published on patients with RTS associated with gastrointestinal abnormalities, to our knowledge the case described herein is the first documentation of a patient with RTS having upper esophageal stenosis.

A 4-year-old boy with subcutaneous tumours is described. These tumours were calcified and had secondary osteoma formation. In addition the patient showed poikiloderma on the face and less prominently on arms and legs. X-ray films of the distal metaphyses of the radius, ulna and tibia revealed irregular mineralisation. Repeated laboratory tests revealed no abnormalities of fat, bone and mineral metabolism. This patient showed a unique combination of symptoms. We propose to call this syndrome: COPS-syndrome (Calcinosis cutis, Osteoma cutis, Poikiloderma and Skeletal abnormalities).

CUGC for hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)

A new family syndrome is described that affected three of seven siblings and another patient who had been abandoned at birth but came from the same area of France. All four patients were young women with a very peculiar phenotype, poikiloderma and greying of the hair, and idiopathic non-arteriosclerotic cerebral calcifications. Pathological studies demonstrated small-vessel hyalinosis due to basal membrane thickening, mainly in the digestive tract, kidneys and calcified areas of the brain. The clinical and biological expressions of these vascular changes varied. Peripheral retinal ischemic syndrome and chorioretinal scars were found in the ocular fundi of three patients. Malabsorption and protein-losing enteropathy was the main problem in all four, and was the cause of one patient's death. A subarachnoid hemorrhage due to a right sylvian aneurysm also occurred in two of the three sisters and was lethal for one. Nephropathy with renal failure and systemic hypertension is the major problem of the two surviving patients.

Thirty-five cases of benign parapsoriasis en plaques, 24 cases of prereticulotic poikiloderma (3 of which were in evolution towards polymorphous lymphomas), 15 cases of lymphoma and 10 cases of other various skin proliferative disorders were studied. For various reasons the first two conditions are preferably indicated as type 1 and type 2 parapsoriasis. Attention is drawn to the possibility of finding a dermal fibro-histiocytary proliferative condition, more often in type 2 parapsoriasis than in type 1. Dysprotidemia, signs of a reactive bone marrow condition, and changes of the tryptophan leads to niacin pathway, as signs of various degrees of damage of connective tissue, were found in type 2 parapsoriasis and lymphomas.

To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of 3H-thymidine-labeled infiltrating cells (3H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the 3H-index is moderately elevated in stage I and high in stage III. The 3H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the smallplaque variant (chronic superficial dermatitis) the 3H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas. Um die Bedeutung der lokalen Zellproliferation im dermalen Infiltrat bei cutanen malignen Lymphomen zu untersuchen, bestimmten wir den Prozentsatz der 3H-Thymidin-markierten Infiltratzellen (3H-Index. Zwischen dem klinischen Stadium der Mycosis fungoides und der Proliferationsaktivitat des dermalen Infiltrats besteht eine lineare Beziehung; im Stadium I ist die Proliferation niedrig, im Stadium III sehr hoch. Nicht erhoht ist der 3H-Index im dermalen Infiltrat beim Sezary-Syndrom, diffusen lymphocytischen Lymphom sowie bei Lymphocytoma benigna cutis. Bei der Parapsoriasis en plaques mussen zwei Formen unterschieden werden: bei der kleinfleckigen Form (“chronic superficial dermatitis”) ist der 3H-Index niedrig, wahrend die grosfleckige Form (Praretikulotisches Poikiloderm) eine starke Proliferationsaktivitat aufweist. Die Untersuchung des Proliferationsverhaltens gibt neue Einblicke in die Pathogenese des dermalen Infiltrats cutaner Lymphome.

Poikiloderma congenitale is a distinctive atrophic dermatosis with onset during infancy. Extracutaneous abnormalities are frequently present. The authors describe a child with poikiloderma congenitale, psychomotor retardation, growth retardation, radial hypoplasia, absence of the thumbs, and foci of abnormal bone in many of the long bones. Although the term Rothmund-Thomson syndrome has been applied to all patients with poikiloderma congenitale regardless of the type of associated extracutaneous abnormalities, patients with severe growth retardation, major skeletal abnormalities, and ectodermal dysplasia who do not have juvenile cataracts appear to represent a distinct subgroup; several patients with these features have been mentally retarded.

Translator's Note. On a recent visit to Paris I was struck by the number of women suffering from diffuse pigmentation of the face. I saw my first cases in the streets and only learnt the nature of the condition when I visited the hospitals, where it is a commonplace in all dermatological clinics.

XERODERMA pigmentosum is a rare hereditary disease of the human skin. After slight exposure to sunlight the skin develops widespread poikiloderma with spotted dyschromia, telangiectasia and atrophy of the epidermis including multiple hyperplasia and the following malignancies of epidermal and dermal origin: basal cell and squamous cell carcinoma, melanoma, fibroma, sarcoma, histiocytoma, neurofibroma and angioma1,2. The molecular basis of light sensitivity and accelerated light induced carcinogenesis of xeroderma pigmentosum may involve a decreased tolerance of individual cells to light3. The initial direct damage is not increased, but the ability of cells to tolerate light induced DNA damage is decreased: investigation of cultured fibroblasts of xeroderma pigmentosum patients showed that these cells are unable to repair ultraviolet-induced single-strand DNA lesions3. The molecular defect lies in the initial stage of the repair process, probably at the endonuclease level4,5.