A Novel Connexin 26 Mutation in a Patient Diagnosed with Keratitis–Ichthyosis–Deafness Syndrome

Keratitis–ichthyosis–deafness syndrome is a rare disorder characterized by erythrokeratoderma, deafness, and keratitis. Scarring alopecia and squamous cell carcinoma can also occur. Most cases described so far were sporadic. Here we present evidence that keratitis–ichthyosis–deafness syndrome is caused by a mutation in the connexin 26 gene. This finding expands the spectrum of disorders caused by defects in connexin 26 and implies the gene in normal corneal function, hair growth, and carcinogenesis

Skin lesions in children admitted to the paediatric intensive care unit: an observational study

We analysed, by a prospective observational study over a 3-year period, the frequency and character of dermatological symptoms and diseases in children admitted to a tertiary general paediatric intensive care unit (PICU) of a university hospital. Skin problems were observed in 42 of 1,800 children admitted. There was a large variability in dermatological diseases in the PICU. In the majority (23/42), the skin problem was a dermatological manifestation of an underlying illness that caused admission to the PICU, e.g. infection, vasculitis or drug reaction. In four of the seven children who died, a direct relation between the dermatological disease and the cause of death could be established. Although the number of patients with relevant dermatological problems was limited, we believe that a skilled paediatric dermatologist is able to contribute to the effectiveness of diagnostic and therapeutic processes in paediatric intensive care patient

Propranolol versus corticosteroids: what should be the treatment of choice in infantile hemangiomas?

Infantile hemangiomas (IHs) are common and benign vascular tumors and usually involute spontaneously. Nevertheless, in some cases, treatment with systemic corticosteroids or propranolol is required. No randomized controlled studies, in which both treatment options were compared, have been performed. A systematic literature review and a retrospective cohort study in the Academic Medical Centre of 56 patients (mean age, 5.5 months; range, 0-40 months; SD, 7.6) with IHs were carried out. These patients were treated with either systemic corticosteroids or propranolol. The outcomes of both treatment options were evaluated and compared. The literature review showed that propranolol resulted in an involution in 100% of the patients, whereas corticosteroids only reached involution in 89%. The mean first response of the IH to propranolol was 3.2 days and of corticosteroids was 8.5 days. In our study sample, the patients treated with propranolol showed a faster and better response than the patients treated with corticosteroids. This is in line with literature findings. Systemic propranolol treatment is more effective for IHs than systemic corticosteroid treatment. Secondly, propranolol elicits a faster response than corticosteroid

Clinical differences between atopic and atopiform dermatitis

BACKGROUND: Atopic dermatitis (AD) has been divided into the "extrinsic" and "intrinsic" type, in which "intrinsic AD" is characterized by the absence of allergen-specific IgE. Still, there is no consensus whether this "intrinsic type" of AD, which we denominate as atopiform dermatitis (AFD), is a distinct entity. OBJECTIVE: A case-control study was performed to compare the clinical and diagnostic features of AD and AFD. METHODS: Patients with a clinical diagnosis of AD were selected. Cases did not have demonstrable allergen-specific IgE. Matched control subjects were tested positive for allergen-specific IgE. Patients were evaluated for medical history, quality of life, disease severity, and Hanifin and Rajka, U.K. and Millennium diagnostic criteria. RESULTS: Eight percent (n = 34) of the selected patients had, in fact, AFD. Female predominance, absence of atopic diseases, later onset of disease, and milder disease severity were observed in AFD. A history of atopy, recurrent conjunctivitis, palmar hyperlinearity, keratosis pilaris, pityriasis alba, and hand and/or food eczema were significantly less present in AFD. Dennie-Morgan fold was positively associated with AFD. LIMITATIONS: Not all patients with negative allergen-specific IgE participated and a relatively small number of AFD patients were studied. CONCLUSIONS: In addition to the absence of allergen-specific IgE, our findings support that AFD is an entity distinct from AD. With a distinction shown between AFD and AD, patient groups will be better defined and more homogeneous. Implications of this distinction will be of importance for preventive and therapeutic advice; diagnostic processes; and for future researc

Quality of life in patients with vascular malformations of the lower extremity

With the exception of capillary malformations (port-wine stains), the adverse psychosocial effects of vascular malformations have not received much attention in the medical literature. We, therefore, studied health related quality of life of patients with vascular malformations located primarily on the lower extremity, who presented to us over a 10-year period. Patient's self-assessment of quality of life was measured by the Multiple Outcomes Study (MOS) Short Form Health Survey Questionnaire (SF-36(TM)). Several possible predictors were also examined. Eighty-one patients (33 mate, 48 female), aged 14-61 years, completed the SF-36. Seventy-one patients (88%) had a low flow lesion. Twenty-three patients (28%) had hypertrophy of the tower extremity, while 11 patients (14%) had hypotrophy. Sixty-nine patients (85%) had the vascular malformation located only on the tower extremity. Six (7%) also had their upper extremity (hand) involved, and 20 patients (24.7%) had > 10% TBSA affected. Eight patients (10%) needed special shoes. Fifty-one patients (63%) had a previously performed MRI, of which 62.7% (32/51) had muscle involvement. Fifty-one patients (63%) had been operated on. Of the 34 patients wearing elastic compression stockings, 25 patients (74%) indicated that they were satisfied with the stockings. Compared to the general population sample, the SF-36 questionnaire indicated that our vascular malformation patients reported impaired vitality and higher levels of pain, white no differences were seen regarding the other dimensions of quality of life. Demographic, clinical and therapy characteristics could explain quality of life only to a limited extent. Explained variability of the SF-36 dimensions ranged from 0% for mental health to 34.5% for rote functioning physical. To our surprise, this study suggests that patients with vascular malformations located primarily on the lower extremity do not have a greatly decreased quality of life when compared to the general Dutch population. (C) 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserve

Baseline Quality of Life in patients with Klippel-Trenaunay syndrome

Background: Klippel-Trenaunay syndrome (KTS) is a congenital group of disorders characterised by vascular malformations (capillary malformation (CM), venous malformation (VM), and lymphatic malformation (LM)) and disturbed growth regulation. The burden caused by KTS symptoms can be evaluated using Quality of Life (QoL)-measuring questionnaires. This study aimed to assess the QoL in KTS patients using the Short Form Health Survey Questionnaire (SF-36) and Skindex-29 questionnaires, and to determine three grades of severity (mild, moderate and severe) according to the scores obtained. In addition, we compared the SF-36 results to those of a general Dutch population sample and a selected group of other chronic conditions. Methods: KTS patients of the Dutch KTS foundation and of two medical centres answered SF-36 and Skindex-29 questionnaires. Control data of validated Dutch population SF-36 scores and literature-acquired scores for other diseases were available. Results: A total of 78 patients were enrolled, of whom 34 (43.6%) were male; the mean age was 39.3 years (SD: 17.1; range: 12-78 years). The Dutch KTS group scored significantly lower than the general Dutch population on all SF-36 scales except Mental Health and Role Emotional. Furthermore, they scored significantly lower than other medical conditions on the Physical Functioning and Bodily Pain scales. According to the Skindex-29 results, KTS patients fall in the categories e symptoms: severe to very severe; emotions: diminutive to mild and functions: mild. The total score is lower than 40, indicating a negligible negative impact on QoL; however, new cut-off values are being calculated. Conclusions: Classification according to severity is important to educate patients accordingly, predict prognosis and set treatments. Especially in cases of severe KTS, physicians should not only be attentive to the physical aspects but also to the psychological and social aspects of KTS. (C) 2009 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeon

Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy

Restrictive dermopathy (RD) is a lethal human genetic disorder characterized by very tight, thin, easily eroded skin, rocker bottom feet, and joint contractures. This disease was recently reported to be associated with a single heterozygous mutation in ZMPSTE24 and hypothesized to be a digenic disorder (Navarro et al, Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 13:2493-2503, 2004). ZMPSTE24 encodes an enzyme necessary for the correct processing and maturation of lamin A, an intermediate filament component of the nuclear envelope. Here we present four unrelated patients with homozygous mutations in ZMPSTE24 and a fifth patient with compound heterozygous mutations in ZMPSTE24. Two of the three different mutations we found are novel, and all are single base insertions that result in messenger RNA frameshifts. As a consequence of the presumed lack of ZMPSTE24 activity, prelamin A, the unprocessed toxic form of lamin A, was detected in the nuclei of both cultured cells and tissue from RD patients, but not in control nuclei. Abnormally aggregated lamin A/C was also observed. These results indicate that RD is an autosomal recessive laminopathy caused by inactivating ZMPSTE24 mutations that result in defective processing and nuclear accumulation of prelamin