Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis.

Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. In the attempt to molecularly classify 17 unrelated Italian patients referred with congenital nonsyndromic ichthyosis, we performed massively parallel sequencing of over 50 ichthyosis-related genes. Genetic data of 300 Italian unaffected subjects were also analyzed to evaluate frequencies of putative disease-causing alleles in our population. For all patients, we identified the molecular cause of the disease. Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations. Three patients had biallelic loss-of-function variants in FLG, whereas 6/11 males were affected by X-linked ichthyosis. Among the 24 different disease-causing alleles we identified, 8 carried novel variants, including a synonymous TGM1 variant that resulted in a splicing defect. Moreover, we generated a priority list of the ichthyosis-related genes that showed a significant number of rare and novel variants in our population. In conclusion, our comprehensive molecular analysis resulted in an effective first-tier test for the early classification of ichthyosis patients. It also expands the genetic, mutational, and phenotypic spectra of inherited ichthyosis and provides new insight into the current understanding of etiologies and epidemiology of this group of rare disorders.

Angioma serpiginosum: Two cases in children and review of literature.

Angioma serpiginosum (AS) is a rare benign vascular lesion that typically arises in early childhood, with a prevalence in female, and then grow up over a period of months/years. It is characterized by small asymptomatic purple-red dots that cluster together and they do not disappear on diascopy. It is mainly localized on the arms but some cases on face and neck have been reported. The etiology of AS is unknown, dermoscopy may aid in the diagnosis but usually the biopsy is necessary. We report 2 cases: one male and one female with angioma serpiginosum, aged 13 and 8 years old.

Consumptive Hypothyroidism due to Hepatic Hemangiomas: A Case Series and Review of the Literature.

Consumptive hypothyroidism (CH) is a rare and potentially overlooked complication of hepatic hemangiomas (HH) overexpressing the enzyme deiodinase, which converts thyroxine (T4) to reverse triiodothyronine (rT3). Materials and methods: Here, we report a case series of 3 patients and a systematic review of the literature. Results: Hypothyroidism (mean serum TSH 52.03 mIU/L) was detected at a mean age of 4.6 months (range 3-6) in 3 infants with infantile hepatic hemangiomas, treated with thyroxine (mean dose 12 µg/kg/day). All received treatment with propranolol (1-3 mg/kg/day) from the mean age of 4 months. Hormonal treatment was stopped at a mean age of 20 months (range 12-30). Hypothyroidism reoccurred in a patient concurrently with the increase of liver lesions, requiring liver transplantation (LT) at age 39 months.Literature review retrieved 42 studies (48 patients): HH (n = 43) were isolated in 24 infants and associated with cutaneous hemangiomas in 19. Hemangiomas were only cutaneous in 5.In the first 43 patients, hypothyroidism was detected at a mean age of 1 month; 21 of 43 patients were prescribed propranolol alone (n = 8) or associated with other medicaments (n = 13); 2 of 43 patients underwent LT. Hormonal treatment consisted of T4 in 35 of 43 patients and T3 in 10.CH associated with only cutaneous and extrahepatic visceral hemangiomas (n = 5), detected at a mean age of 7 months (TSH mean levels at diagnosis of 150.3 mIU/L). Three of 5 patients received treatment with propranolol ± other medicaments. All 5 patients were treated with T4. Conclusions: Periodical thyroid function assessment is necessary in patients with hepatic hemangiomas, particularly when lesions' size and number increase rapidly.

Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams.

BACKGROUND AND PURPOSE: The purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy. MATERIALS AND METHODS: A group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale. RESULTS: All patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage. CONCLUSIONS: The preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy.