Summary Background Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype–phenotype correlation in some populations. Objectives We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype–phenotype correlation. Methods Deep phenotyping was undertaken by history‐taking and clinical examination. DNA was screened for mutations using a next‐generation sequencing ichthyosis gene panel and Sanger sequencing. Results Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self‐improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. Conclusions These data refine genotype–phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype–phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Summary Background Oral propranolol is widely prescribed as first‐line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. Objectives The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. Methods Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. Results The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg−1 per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg−1 vs. 2 mg kg−1 vs. > 2 mg kg−1, the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33–1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04–5·46, P = 0·04, Ptrend < 0·001. Conclusions The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

NB-UVB is clinically effective and improves quality of life in children with moderate-to-severe eczema. The effect is maintained for 6 months after treatment.

SUMMARY There is good correlation between the specific gravity and osmolality of urine obtained from neonates and adults, if specimens contain neither protein nor glucose. The regression equations between specific gravity and osmolality, however, differ considerably between the two age groups, maturation to the adult regression occurring within the first 5 years of life. Specifically derived regression equations should therefore be used when predicting urine osmolality from measurement of specific gravity in neonates.The osmolality of urine is the definitive measure of its concentration. Under normal physiological conditions low urine osmolality equates with hydration, and high urine osmolality with dehydration. The ability of neonates to concentrate urine is lower than that of adults, but the capacity to dilute urine is similar. In a non-uraemic, normonatraemic, and normoglycaemic neonate, therefore, urine osmolality maintained between 75 mosmol/kg-300 mosmol/ kg indicates adequate hydration; values outside these ranges suggest overhydration and dehydration, respectively.'The necessity for monitoring urine osmolality in neonates to estimate fluid balance may make heavy demands on the laboratory. Osmometers are expensive and unsuitable for use in the wards without the help of a technician. The specific gravity of urine, traditionally measured in the ward, also reflects concentration, but the prediction of urine osmolality from specific gravity measurement may be unreliable in unskilled hands.2 In addition, abnormal concentrations of glucose and protein in the urine cause appreciable increases in specific gravity without affecting osmolality. Finally, measurement by traditional flotation hydrometry requires a large volume of urine. All these factors militate against the use of specific gravity as a measure of urine concentration in neonates.Despite recent interest in the measurement of specific gravity as an indicator of urine concentration in children, the influence of age on the relation between specific gravity and osmolality has niot been defined.3 We studied the association between urine specific gravity measured by refractometry, and osmolality, to assess the practicability of measuring the urine concentration of neoniates accurately in the ward; we also assessed the influence of age on the relation between specific gravity and osmolality. Material and methodsWe collected 100 urine samples from 21 neonates in the special care baby unit; the babies had been born at 28 to 32 weeks' gestation and mean (SD) weight was 2100 (940) g. Single specimens of urine were collected from 22 healthy babies born at full term, 88 children from a paediaitric ward (age range 1-70 months), and from 59 healthy adults. The specimens were not taken at a particular time, nor were they preserved. Urine was tested for the presence of glucose and protein using the Ames Uristix, and those specimens showing positive results were excluded.Osmolality wCas measured on fresh urine slmples by freezing point depression osmometry (Advanced Ins...

Background: Review of the literature reveals that congenital malignant melanoma is an exceptionally rare occurrence and has a generally poor prognosis when it does occur. However, benign proliferative melanocytic lesions are known to occur within giant congenital nevi (GCN). This entity is not well recognized and can be confused clinically and histologically with malignant change.Observations: We report 2 cases of GCN in neonates demonstrating benign proliferating nodules present at birth. An initial diagnosis of malignant melanoma was assumed in both cases. Careful histologic analysis, however, revealed these lesions to be benign, as did longterm follow-up of 3.5 years, with both patients remain-