Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations.

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations.

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations.

Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown.

Transcriptional regulator PRDM12 is essential for human pain perception.

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP).

Ophthalmic manifestations of vitamin A and D deficiency in two autistic teenagers: case reports and a review of the literature.

We describe the cases of 2 autistic children with ophthalmic and systemic manifestations of vitamin A deficiency due to food faddism. Although vitamin A deficiency is common in the developing world, reports in developed societies are rare. Our patients presented over a 1-year period.

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis.

Background: Atopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.

Rapidly involuting congenital hemangioma with pustules: two cases.

Rapidly involuting congenital hemangiomas (RICHs) are rare tumors that usually present as well-defined bluish or violaceous plaques or tumors with scattered telangiectasias and central or peripheral pallor. We report two previously unreported cases of RICH with associated pustules.

Neonatal lupus syndrome associated with ribonucleoprotein antibodies.

Neonatal lupus erythematosus (NLE) is a rare acquired autoimmune disease caused by transplacental transfer of maternal immunoglobulin G antibodies to the fetus. NLE has well-recognized cutaneous features and may also manifest in other organs. The majority of cases are associated with Ro/SSA and La/SSB antibodies.

Use of systemic corticosteroids in management of a large congenital haemangioma of the scalp.

Congenital haemangiomas are rare and are estimated to have a combined incidence of less than 3% of all infantile haemangiomas. They are fully grown at birth, having undergone their proliferative phase in utero. Congenital hemangiomas can present at birth or in some cases can be detected antenatally on imaging.

Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency.

Background: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) compared with that seen in patients with AD without these mutations (AD(NON-FLG)).

Objectives: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD(FLG) versus patients with AD(NON-FLG).

PHACE syndrome: MRI of intracerebral vascular anomalies and clinical findings in a series of 12 patients.

Background: PHACE (posterior fossa defects, haemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities) syndrome describes a constellation of abnormalities that can occur in association with segmental craniofacial infantile haemangioma.

Objective: To report the spectrum of clinical and imaging abnormalities seen in a cohort of children.

Materials And Methods: A retrospective review of the clinical and imaging records of all patients diagnosed with PHACE syndrome between 1998 and 2009 was performed.

Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes.

Background: Filaggrin (FLG) has a central role in the pathogenesis of atopic dermatitis (AD). FLG is a complex repetitive gene; highly population-specific mutations and multiple rare mutations make routine genotyping complex. Furthermore, the mechanistic pathways through which mutations in FLG predispose to AD are unclear.

Care of epidermolysis bullosa in Ireland.

Advances in the medical care of epidermolysis bullosa (EB) have led to the development of National Service Centers for EB in many countries worldwide. The exemplary model of care to children and adults with EB in the United Kingdom, combined with the knowledge that people with EB were travelling to the United Kingdom for treatment, encouraged the development of the Irish national service. Dystrophic Epidermolysis Bullosa Research Association of Ireland, founded in 1988 played a pivotal role in this development.

Mediastinal and neck kaposiform hemangioendothelioma: report of three cases.

Kaposiform hemangioendothelioma is an aggressive vascular tumor, named for its striking histologic resemblance to Kaposi sarcoma and locally invasive growth. Mortality is high, and ranges from 10% to 24% for all kaposiform hemangioendothelioma lesions, with a significantly higher mortality for deep soft-tissue or visceral lesions occurring in infants less than 6 months. Mediastinal and neck kaposiform hemangioendothelioma in particular merit special discussion, as involvement of these critical anatomic locations results in significant site-specific therapeutic challenges due to invasion of vital structures, inherent delays in establishing histopathologic confirmation, and difficulties in monitoring disease status.

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk.

Background: Polymorphisms in the serine protease inhibitor gene serine peptidase inhibitor Kazal type 5 (SPINK5) and the serine protease kallikrein-related peptidase 7 gene (KLK7) appear to confer risk to eczema in some cohorts, but these findings have not been widely replicated. These genes encode proteins thought to be involved in the regulation of posttranslation processing of filaggrin (FLG), the strongest identified genetic risk factor for eczema to date.

Objectives: We sought to clarify the individual risk of eczema conferred by the SPINK5 polymorphism rs2303067 (Glu420Lys) and a previously described insertion in the 3' untranslated region of KLK7 and to examine potential epistatic effects between these variants and FLG mutations.

Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema.

We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent.

Response to IL-1-receptor antagonist in a child with familial cold autoinflammatory syndrome.

Familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic, cutaneous, articular syndrome are related disorders associated with mutations in the CIAS1 gene. They appear to represent a continuum of one disease characterized by IL-1-mediated inflammation. Until recently, these conditions have been difficult to treat; however, with the advent of IL-1-receptor antagonist therapy, many reports of successful treatment of patients with these autoinflammatory diseases have emerged in the past 2 years.

Rhombencephalosynapsis presenting antenatally with ventriculomegaly/hydrocephalus in a likely case of Gomez-López-Hernández syndrome.

Rhombencephalosynapsis is a rare cerebellar malformation that can be associated with anomalies of the cerebral hemispheres and variable degrees of neurodevelopmental delay. A syndromic association, comprising rhombencephalosynapsis, developmental delay, scalp alopecia and trigeminal anaesthesia (Gomez-López-Hernández syndrome) has been described in seven individuals. We report the case of a 2-year-old boy with rhombencephalosynapsis, and review the evidence for a possible diagnosis of Gomez-López-Hernández syndrome.

The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia.

Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.

ABCA12 is the major harlequin ichthyosis gene.

Harlequin ichthyosis (HI) is the most severe form of autosomal-recessive, congenital ichthyosis. Affected infants have markedly impaired barrier function and are more susceptible to infection. Abnormalities in the localization of epidermal lipids as well as abnormal lamellar granule formation are features of HI skin.

Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis.

Mutations in the filament aggregating protein (filaggrin) gene have recently been identified as the cause of the common genetic skin disorder ichthyosis vulgaris (IV), the most prevalent inherited disorder of keratinization. The main characteristics of IV are fine-scale on the arms and legs, palmar hyperlinearity, and keratosis pilaris. Here, we have studied six Irish families with IV for mutations in filaggrin.