Congenital Ichthyosiform Research Articles

Characteristics of subpopulation composition of peripheral blood lymphocytes in children with different forms of congenital ichthyosis

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Bilateral ectropion in collodion baby - Three case reports

The term ‘Collodion baby’ is used for the new-borns who are born in a parchment like membrane which is shiny, taut, waxy and appears like an extra layer of skin that has a collodion-like quality covering the whole body. It is not a specific diagnosis or disorder but rather a descriptive term. It is found in some forms of congenital ichthyosis. This membrane is shed around 2 weeks from birth. On shedding of membrane dry rough scaly skin like that of fish is visible. Other findings seen in our cases include ectropion and flattening of the nasal bridge. Neonates require careful monitoring and appropriate supportive treatment to decrease morbidity and mortality related to the disorder. We report here three rare cases of collodion baby with congenital ectropion. Keywords: Collodion baby, Lamellar ichthyosis, Ectropion.

Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis

Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI. To expand the genotypic spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to use BSI genotypes to draw inferences about the temperature sensitivity of TGM1 mutations. A total of 16 participants with BSI from 13 kindreds were identified from 6 academic medical centers. A detailed clinical history was obtained from each participant, including phenotypic presentation at birth and disease course. Each participant underwent targeted sequencing of TGM1. Phenotypic and genotypic characteristics in these patients from birth onward. Of the 16 participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39 years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8 TGM1 missense mutations that to our knowledge have not been previously reported in BSI: 5 have been previously described in non-temperature-sensitive forms of congenital ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations. Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating that these mutations are temperature sensitive. Seven of 10 probands with a compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315, providing evidence that mutations at these sites are temperature sensitive and highlighting the importance of these residues in the pathogenesis of BSI. Our findings expand the genotypic spectrum of BSI and the understanding of temperature sensitivity of TGM1 mutations. Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1 ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.

Ductal cyst of lacrimal gland in patient with congenital ichthyosiform erythroderma

Resumo A ictiose lamelar e uma doenca congenita de heranca autossomica recessiva que se caracteriza clinicamente por descamacao de toda a superficie corporal devido hiperceratose mucocutânea que pode levar a comprometimento oftalmologico. Neste estudo relatamos um caso de cisto ductal de glândula lacrimal em paciente portador de ictiose lamelar atendido no Hospital Oftalmologico de Anapolis.

Epidermolytic hyperkeratosis in verrucous epidermal nevus

Epidermal nevi are hamartomas that are characterized by hyperplasia of the epidermis and adnexal structures. Most cases arise sporadically during development of the embryo, but familial patterns of inheritance have been observed. Only 5-10% of patients with verrucous epidermal nevus show histological features of epidermolytic hyperkeratosis. This has a significant clinical importance as this patient carry the risk of parenting a child of congenital bullous ichthyosiform erythroderma. A 7-year-old boy born of non-consanguineous marriage presented with non-pruritic multiple verrucous papules that coalesce to form well-demarcated, skin colored to brown, papillomatous plaques over the right side of abdomen, right loin, right legs including a cauliflower like verrucous plaque over the umbilicus distributed along the line of Blaschko noticed since 1-year of age. Oral cavity, palms and soles were spared. Developmental milestones were normal. A diagnosis of verrucous epidermal nevus was made. Histology showed hyperkeratosis, papillomatosis and vacuolization of the cells in the stratum spinosum and granulosum with keratohyalin granules. Routine examination of blood and chest X-ray were normal. This case is being reported to highlight the rare histological features and to re-emphasize the importance of routine histological examination and genetic counseling in all cases of verrucous epidermal nevus.

Lamellar ichthyosis with severe bilateral ectropion and self-healing collodion membrane

Congenital ichthyosis is a type of generalized hyperkeratinization of the skin at birth. Three forms of congenital ichthyosis have been defined based on clinical aspects and severity: (1) congenital ichthyosis mitis; (2) congenital ichthyosis tarda; and (3) congenital ichthyosis gravis. Desquamation of the parchment-like hyperkeratinized skin begins shortly after birth and may require several weeks to complete. Skin alterations in the eyelid cause shortening of the anterior lamella, subsequently resulting in ectropion. This affects the upper eyelid more often than the lower eyelid and can lead to complications such as chronic palpebral or bulbar conjunctivitis and keratinization or exposure keratopathy. In this paper, we present two case reports illustrating the course of ichthyosis congenita mitis and ichthyosis congenita tarda.

Novel transglutaminase 1 mutations in patients affected by lamellar ichthyosis

Lamellar Ichthyosis (LI) is a form of congenital ichthyosis that is caused by mutations in the TGM1 gene that encodes for the transglutaminase 1 (TG1) enzyme. Functional inactivation of TG1 could be due to mutations, deletion or insertions. In this study, we have screened 16 patients affected by LI and found six new mutations: two transition/transversion (R37G, V112A), two nonsense mutations and two putative splice site both leading to a premature stop codon. The mutations are localized in exons 2 (N-terminal domain), 5, 11 (central catalytic domain), and none is located in the two beta-barrel C-terminal domains. In conclusion, this study expands the current knowledge on TGM1 mutation spectrum, increasing the characterization of mutations would provide more accurate prenatal genetic counselling for parents at-risk individuals.

Harlequin ichthyosis: a review of 50 cases and update of ABCA12 mutation analysis

Mutations in the ABCA12 gene underlie the most severe form of recessive congenital ichthyosis, Harlequin ichthyosis (HI). Due to the rarity of cases, there are no large series reporting the outcomes of babies born with HI. To improve the care of HI families, the authors have established a major referral centre for HI genetic screening and conducted an international study of 50 children born with this condition. The aim of this study is to assess the clinical outcomes of patients with HI referred to us for ABCA12 analysis and thereby report neonatal complications and long-term sequelae. Secondly, this study aims to identify novel mutations to facilitate prenatal diagnosis. Referring physicians were asked to review medical notes and retrospectively complete a clinical questionnaire. Adults and children over five were asked to complete a dermatology life quality index (DLQI) questionnaire. Mutation analysis was performed using PCR and sequencing but in one consanguineous case, reverse transcriptase-PCR (RT-PCR) on a parental skin biopsy was performed, followed by copy number analysis. Fifty responses were received. All infants had a typical appearance at birth and thereafter developed a persistent, diffuse scaly erythema with hair thinning and nail deformities. In most cases, acitretin was started shortly after birth. Approximately 54% of neonates survived into childhood and beyond. Mortality was associated with respiratory distress and sepsis. Early childhood skin infections with Staphylococcus, Streptococcus, Pseudomonas and MRSA were reported in one third. Problems maintaining weight necessitating nasogastric feeding in infancy and a high-calorie diet thereafter were seen in 58%. Older children experienced joint pain and there were two cases of inflammatory arthritis. While most children attended a mainstream school, 57% in the UK needed statementing. Despite the severity of the disease, the average children9s DLQI score was only 10/30. Eight novel ABCA12 mutations were identified and another three patients have been shown to harbour the common Pakistani mutation 7322delC. In the consanguineous case, a deletion of exons 12–15 was detected by RT-PCR and subsequently confirmed using copy number analysis. This is the first large-scale study of HI and provides important prognostic information for clinicians and affected families.

Effect of topical tazarotene in the treatment of congenital ichthyoses.

The clinical efficacy and tolerability of the topical receptor-selective retinoid tazarotene in the treatment of congenital ichthyoses was investigated. Twelve consecutive patients with different forms of congenital ichthyosis were enrolled in an open, non-randomized, intraindividually controlled, half-side pilot study. Diagnoses were X-linked recessive ichthyosis, non-erythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant ichthyosis vulgaris and ichthyosis bullosa of Siemens (IBS). Tazarotene 0.05% gel was applied unilaterally daily on a defined body area measuring 10% of the body surface area. The contralateral side was treated with an ointment containing 10% urea. After 14 days, application frequency was reduced to three times a week, and stopped after another 2 weeks. The follow-up period was 3 months. Reduction in scaling and roughness was used to assess the clinical response in the tazarotene-treated area compared with the control area. Clinical and laboratory assessments were performed every 14 days during the trial. Unilateral improvement in favour of the tazarotene-treated side was observed in nine of 12 patients (75%). Four patients (33%) achieved an excellent response and four (33%) achieved a good response. No therapeutic effect was seen in patients with IBS. The remission persisted during the reduction phase and after discontinuation for up to 2 months. Local irritation in three patients was the only side-effect detectable. Short-term topical application of tazarotene 0.05% gel is a very effective and well-tolerated treatment modality in different forms of congenital ichthyoses and may be an alternative to systemic retinoid therapy.

Inherited ichthyoses: a review of the histology of the skin.

The histology of skin biopsies from 46 cases of different forms of congenital ichthyosis was reviewed. Sections were examined for hyperkeratosis, follicular keratosis, appearance of the granular layer, epidermal thickness, tonofilament clumps, epidermal vacuolation, spongiosis, bullae and dyskeratosis, appearance of the basal layer, inflammation, mitoses, and adnexae. A detailed description of the histological features of each type of ichtnyosis studied is presented. Some ichthyoses can be recognized on routine hematoxylin and eosin staining (bullous ichthyosiform erythroderma, Netherton's syndrome, and neutral lipid storage disease); some forms require frozen sections to demonstrate fat (neutral lipid storage disease) or enzyme activity (Sjögren-Larsson syndrome). Protein electrophoresis and enzymology are necessary for X-linked recessive ichthyosis. A close liaison with the clinicians is essential for the diagnosis of all types of ichthyosis, and combined studies including routine histopathology, electron microscopy, and frozen sections may be required for the diagnosis.

Ultrastructural identification of basic abnormalities as clues to genetic disorders of the epidermis.

The present article discusses specific, directly gene-dependent ultrastructural markers of dominantly inherited epidermal disorders that serve as clues to their underlying molecular genetic abnormalities. These are epidermolysis bullosa simplex Koebner and Weber-Cockayne with rupture or non-assembly of basal cell keratins and point mutations in keratins 5 and 14. Clumping of basal cell keratins is pathognomonic of EB Dowling-Meara and caused by mutations in hot spots of the rod domain of K5 and K 14. Clumps and aggregates of basal keratins occur side by side in the same cell and thus do not indicate specific different types of mutations. Similar clumping of suprabasal keratins in bullous CIE Brocq and in palmoplantar keratoderma Voerner have been assigned to identical types of mutations in the same critical position of the rod domain in K 1, K 10, and K 9, respectively. Highly unusual tubular keratins are pathognomonic of another dominant palmoplantar keratoderma type the genetic basis of which still awaits elucidation. Shell formation of (low molecular weight?) keratins in ichthyosis hystrix Curth-Macklin is not linked to the keratin gene clusters on chromosomes 12 and 17 and might be related to regulatory genes of keratin expression. Suprabasal shells in congenital reticular ichthyosiform erythroderma do not consist of keratins but resemble glycoprotein networks. Finally, the keratohyalin abnormality in ichthyosis vulgaris was the clue for the identification of a filaggrin deficiency, at the same time giving evidence to the heterogeneity of keratohyalin proteins.

Keratinocyte proliferation in epidermal keratinocyte disorders evaluated through PCNA/cyclin immunolabelling and AgNOR counting.

The assessment of cell proliferation is important to our understanding of hyperproliferative disorders. In this work we evaluated the proliferation characteristics of epidermal keratinocytes in diseases with abnormal keratinization by two different methods (immunostaining for the proliferating cell nuclear antigen--PCNA and histochemical staining for nucleolar organizer region--associated argyrophilic proteins--AgNORs). Twenty-seven specimens from diseases with an abnormal keratinization were studied and compared with specimens of normal human skin. As compared with the latter, the numbers of PCNA-positive epidermal keratinocytes were increased in psoriasis, congenital non-bullous ichthyosiform erythroderma, epidermolytic hyperkeratosis and chronic dermatitis and decreased in ichthyosis vulgaris, X-linked ichthyosis and pityriasis rubra pilaris. In most cases a parallel modification of AgNORs was found. We conclude that although PCNA immunolabelling and AgNOR staining do not provide strictly correlated values, both appear as useful markers for the assessment of keratinocyte proliferation in epidermal disorders.

Secondary Hyperparathyroidism in Patients With Ichthyosis Is Not Caused by Vitamin D Deficiency or Ingestion of Retinoids

To the Editor.— We recently reported that five of 15 patients with various disorders of keratinization had secondary hyperparathyroidism. 1 We now confirm and extend those observations to a larger, totally separate group of patients. Patients and Methods.— Families with epidermolytic hyperkeratosis, lamellar ichthyosis, congenital nonbullous ichthyosiform erythroderma, ichthyosis vulgaris, and Darier's disease answered an advertisement to participate in studies on the genetic basis of their disease(s). Diagnoses were established by clinical findings, inheritance pattern, and skin biopsy specimens of at least one member of each family. Coded serum and plasma samples were immediately frozen and shipped to New Haven, Conn, for analysis of parathyroid hormone (PTH), creatinine, calcium, 25(OH) vitamin D, and 1,25 (OH) 2 vitamin D as previously described. 1 Results.— Samples from 65 patients were analyzed. The patients fell into two distinct groups: those with normal serum PTH values and those with PTH levels at least 1.8

Congenital ichthyosis with hypogonadism and growth retardation ? a new syndrome with peculiar ultrastructural features

A male patient presented with a congenital ichthyosis clinically characterized by generalized erythroderma, fine scaling on the trunk and palmoplantar hyperkeratoses with severely affected nails. The acanthotic epidermis was characterized by hyperproliferation with a large quantity of mitoses and extremely suppressed keratinization without a normal granular layer. The horny layer was parakeratotic and contained remnants of cell debris and lipid droplets. Ultrastructurally the prickle cell layer was characterized by binuclear cells, oedematization of the keratinocytes and isolated dyskeratotic cells. Some suprabasal cells showed unusual morphological features, containing nuclei with cytoplasmic pseudoinclusions, sometimes leading to a complete disintegration of the nuclear structure, and bowl- and lens-shaped accumulations of a filamentous material. Instead of normal tonofibrils, the aggregated material consisted of fine interlacing filaments. The latter are compared with the filamentous shells in ichthyosis hystrix Curth-Macklin and congenital reticular ichthyosiform erythroderma. The clinical symptomatology--congenital ichthyosis, growth retardation, secondary hypogonadism, hepatomegaly--and the ultrastructural characteristics of the keratinization disorder indicate that the present case cannot be considered as a subtype of the recessively inherited ichthyosis congenita group, but suggest a new syndrome as a separate nosologic entity.

Congenital Migratory Ichthyosiform Dermatosis With Neurologic and Ophthalmologic Abnormalities

We encountered two patients with a congenital migratory ichthyosiform dermatosis, retinal colobomas, conductive hearing loss, seizures, mental retardation, and similar facial features. The results of electron microscopic studies performed on skin biopsy specimens from the patients differed significantly from those of previously reported cases of ichthyosiform dermatoses with associated neurologic and ophthalmologic abnormalities; they appear to represent a new neuroectodermal syndrome.

Alopecia ichthyotica

Scarring patchy alopecia is a characteristic feature of various forms of congenital ichthyosis (congenital ichthyosiform erythroderma). 4 patients presenting this scalp disease are described. The hair loss is obviously a consequence of the ichthyosiform erythroderma, and therefore we propose for this type of pseudopelade the term alopecia ichthyotica.