Trichothiodystrophy-like hair abnormalities in a child with keratitis ichthyosis deafness syndrome

Abstract:  Keratitis ichthyosis deafness syndrome is a rare congenital ectodermal disorder. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis-like skin lesions, hearing loss, and vascularizing keratitis. We report the clinical and molecular findings in a 5-year-old girl with keratitis ichthyosis deafness syndrome. DNA sequencing in our patient revealed a p.Ser17Phe mutation in GJB2. Besides the typical clinical features of keratitis ichthyosis deafness syndrome, a peculiar intriguing finding not previously described in the literature in this condition was that polarizing light microscopy of the scalp hair in our patient revealed striking bright and dark bands as seen in trichothiodystrophy. Amino acid analysis of the hair sample also disclosed a reduced cysteine index. We emphasize that it would be of great benefit to examine hair shafts in other patients with keratitis ichthyosis deafness syndrome for trichothiodystrophy-like abnormalities.     

Woolly hair--study of a family

A white English family is described with autosomal dominant woolly wiry hair. The propositus had woolly curly scalp hair, congenital perceptive deafness and dominant ichthyosis vulgaris. Her brother was epileptic and also deaf, but his skin and hair were normal and a male first cousin had dominant ichthyosis vulgaris but normal hair and hearing. Consanguinity was an interesting additional feature in this family.     

Ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis, growth retardation, and metaphyseal dysplasia (Shwachman syndrome). Report of a case with extensive skin lesions (clinical, histological, and ultrastructural findings)

The Shwachman syndrome comprises exocrine pancreatic insufficiency, growth retardation, and bone marrow hypoplasia resulting in neutropenia. Clinical, morphological, and ultrastructural studies, as well as hair analysis, were performed in a patient with Shwachman's syndrome and severe ichthyosis. Clinical findings were lamellar ichthyosiform desquamation on the extremities. The hair was scanty and short on the scalp, in the eyelashes, and in the eyebrows. The nails were hyperkeratotic. Morphologic findings were slight, regular acanthosis and severe diffuse hyperkeratosis with variable parakeratosis. The granular layer was thickened. The papillary dermis showed very slight perivascular lymphocyte infiltration. The most prominent ultrastructural finding was the presence of solitary or multiple droplets of varying size in the cytoplasm of the keratinocytes. Hair analysis revealed no abnormalities; the cystine concentration in hair specimens was normal.     

A Patient with Tay''s Syndrome

A 4-year-old girl with Tay's syndrome had the typical features of congenital ichthyosis and the peculiar anomaly of hair growth, trichothiodystrophy. Her hair shafts were brittle and showed alternating light and dark banding when examined microscopically between polarizing filters. Her hair cystine content was 4.6% (control 8.4%).     

Two cases of lamellar ichthyosis with unusual hair shaft abnormalities

The authors describe two brothers presenting the clinical picture of lamellar ichthyosis. The scanning electron microscopy and transmission electron microscopy study of their hair demonstrated important recurrent anomalies of the hair shaft.     

X性联锁遗传鱼鳞病一家系的STS基因研究

目的 研究一 X性联锁遗传鱼鳞病(XLI)家系基因突变,探讨基因突变与临床表现的关系,为进一步开展基因诊断和基因治疗奠定基础。方法 应用PCR方法扩增家系中的先证者及其母亲及与该家系无关的50例正常人外周血基因组DNA STS基因的第一外显子和第十外显子。以角蛋白hHb6为引物,作内对照。结果 家系中先证者的STS基因全部缺失,而先证者之母和与该家系无关的50例正常人未发现缺失。先证者及先证者之母的内对照引物PCR扩增后都有产物。结论 该XLI家系存在STS基因缺失,该缺失引发出XLI特有的皮肤病变。     

Trichothiodystrophy

Trichothiodystrophy is a congenital dysplasia of hairs characterized by: a pathognomonic image of the hair shaft under polarized light (the hair is plaited with alternately dark and light oblique bands) and trichoschisis with a clear-cut break; a deficiency of sulphurated aminoacids in the hair. We report a case where trichothiodystrophy was associated with abnormalities of the nails, teeth and eyes, growth and mental retardation, neurological syndrome and hypogonadism. From this case and a review of the cases published so far the following points emerge: 1. Congenital abnormalities of the neuroectodermal system are frequent. They include: skin lesions, such as ichthyosis, photosensitivity and atopic eczema; ungueal dysplasia; dysmorphic syndrome; growth and mental retardation; hypogonadism; neurological and ophthalmic abnormalities. 2. The condition seems to be transmitted as an autosomal recessive trait. A common element, dysplasia, enables us to include in the same nosological group as trichothiodystrophy a number of other pathological conditions, viz.: syndromes hitherto described under various names but almost identical, such as Brown's syndrome and BIDS syndrome (brittle hair, intellectual deficit, decreased fertility, small stature); IBIDS and PIBIDS syndromes which, in addition to the former, comprise ichthyosis and photosensitivity, as well as Tay's syndrome (characterized by the presence in all cases of ichthyosis associated with hair dysplasia); and perhaps some anecdotic cases with either a pathognomonic image under polarized light or a suggestive biochemical profile. Finally, since typical trichothiodystrophy has been reported in patients with Siemens' syndrome or with Marviesco-Sj?gren syndrome, these two syndromes may perhaps also be classified in the same category, as borderline forms of the disease.     

Long-term oral treatment of two pronounced ichthyotic conditions: lamellar ichthyosis and epidermolytic hyperkeratosis with the aromatic retinoid, Tigason (RO 10-9359)

Five patients suffering from lamellar ichthyosis and 3 from epidermolytic hyperkeratosis (previously called non-bullous and bullous congenital ichthyosiform erythroderma) were treated from 11 to 52 months with the synthetic aromatic retinoid Tigason (RO 10-9359). In all cases of lamellar ichthyosis the results were judged as good to excellent, while none of the patients with epidermolytic hyperkeratosis gave more than a slight response. The reason for the poorer results in the latter condition was that effective therapeutic dosages in relation to ichthyosis invariably produced increased blistering. These and other side effects such as cheilitis, mild dryness of mucous membranes, slight hair loss, and pruritus, in no case necessitated discontinuation of the drug.     

Trichoscopy as a diagnostic tool in trichorrhexis invaginata and Netherton syndrome

Netherton syndrome is a rare autosomal recessive disease characterized by erythroderma, ichthyosis linearis circumflexa, atopy, failure to thrive and a specific hair shaft abnormality called trichorrhexis invaginata or bamboo hair, considered pathognomonic. We report the case of a 4-year-old boy with erythroderma since birth, growth deficit and chronic diarrhea. Trichoscopy was used to visualize typical bamboo and "golf tee" hair and of key importance to diagnose Netherton syndrome. We suggest the use of this procedure in all children diagnosed with erythroderma.     

Ichthyosis cribriformis: A new entity?

A 22-year-old woman had an unusual congenital skin disorder in the form of ichthyosis characterized by innumerable keratotic plugs, resulting in a peculiar sievelike appearance. On histopathologic examination the epidermis showed a pronounced orthohyperkeratosis. The keratotic plugs seemed to emerge from the infundibular region of hair follicles. Immunohistochemical characterization revealed a normal keratin and filaggrin expression. Oral treatment with isotretinoin resulted in a reduction of the hyperkeratosis. Because we could not find any previously reported similar case, we propose the new name "ichthyosis cribriformis," which means "sievelike ichthyosis."     

Do you know this syndrome? Ichthyosis associated with neurological condition and alteration of hairs

Trichothiodystrophy refers to a heterogeneous group of rare genetic diseases that affects neuroectodermal-derived tissues with multisystem involvement. The hallmark of these syndromes is the deficiency of sulfur in hair matrix proteins, leading to short and brittle hair. Few cases of this rare disorder have been published. The authors report a case of trichothiodystrophy in a male infant with ichthyosis, photosensitivity, spastic paraparesis, short stature, and neurologic and psychomotor retardation. Diagnosis was based on clinical and microscopic features of hair samples.     

Annular epidermolytic ichthyosis: a case report and literature review

Annular epidermolytic ichthyosis is a rare subtype of epidermolytic ichthyosis that is characterized by erythematous, polycyclic, and migratory scaly plaques accompanied by palmoplantar keratoderma. This report presents the case of an 8-year-old girl who developed migratory, erythematous, scaly plaques associated with palmoplantar keratoderma. The initial hypothesis was erythrokeratodermia variabilis et progressiva; however, the finding of epidermolytic hyperkeratosis in histopathological examination led to the diagnosis of annular epidermolytic ichthyosis.     

Ichthyosis, follicular atrophoderma, and hypotrichosis caused by mutations in ST14 is associated with impaired profilaggrin processing

Congenital ichthyosis encompasses a heterogeneous group of disorders of cornification. Isolated forms and syndromic ichthyosis can be differentiated. We have analyzed two consanguineous families from the United Arab Emirates and Turkey with an autosomal recessive syndrome of diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse nonscarring hypotrichosis, marked hypohidrosis, and woolly hair (OMIM 602400). By genome-wide analysis, we found a homozygous interval on chromosome 11q24-q25 and obtained a LOD score of 4.0 at D11S910. We identified a homozygous splice-site mutation in the Arab patients and a frame-shift deletion in the Turkish patient in the gene suppression of tumorigenicity-14 (ST14). The product of ST14, matriptase, is a type II transmembrane serine protease synthesized in most human epithelia. Two missense mutations in ST14 were recently described in patients with a phenotype of ichthyosis and hypotrichosis, indicating diverse activities of matriptase in the epidermis and hair follicles. Here we have further demonstrated the loss of matriptase in differentiated patient keratinocytes, reduced proteolytic activation of prostasin, and disturbed processing of profilaggrin. As filaggrin monomers play a pivotal role in epidermal barrier formation, these findings reveal the link between congenital disorders of keratinization and filaggrin processing in the human skin.     

Quantification of n-alkanes in stratum corneum in the hereditary ichthyoses

Chromatographic assay of n-alkanes in skin showed detectable levels in normal controls and in patients with various forms of hereditary ichthyosis. Raised n-alkanes were found in some, but not all, patients with non-bullous and bullous ichthyosiform erythroderma and in individual patients with lamellar ichthyosis, ichthyosis vulgaris and Netherton's syndrome. The finding of elevated scale n-alkanes is neither consistent in ichthyosis, nor specific to any one type of ichthyosis, and n-alkane assay is not helpful in distinguishing one type of hereditary ichthyosis from another. The source of n-alkanes in ichthyotic scale and their role, if any, in the pathogenesis of ichthyosis remain obscure.     

Ichthyosis follicularis with alopecia and photophobia (IFAP) syndrome

A 12-year-old boy born of a nonconsanguineous marriage presented with dry rough skin and photophobia since birth. His growth and developmental milestones were normal and there was no history of any neurological problem, hearing deficit or scarring around the hair follicles. Cutaneous examination revealed diffuse thinning of scalp hair with loss of eyebrows and eyelashes and a sandpapery texture of the skin all over the body, suggestive of ichthyosis follicularis with alopecia and photophobia syndrome.     

Lichenoid folliculitis of the scalp in four patients with ichthyosiform skin disorders and cicatricial alopecia

Ichthyosis is a heterogeneous group of inherited skin disorders characterized by a defect of keratinization. Patients diagnosed with lamellar ichthyosis (LI) and some ichthyosiform syndromes, such as the Conradi‐Hünermann‐Happle syndrome (CHHS), usually present with hair loss. Even though only few dermatologic complaints carry as many emotional overtones as hair loss, there are very few data available in the literature regarding scalp histopathological features in ichthyosis. A better understanding of scalp changes in such context may result in new therapeutic strategies that in turn would enhance patients' self‐esteem and quality of life. The aim of this paper is to describe the scalp histopathological findings of four young patients with cicatricial alopecia: three diagnosed as having LI and the fourth with CHHS.     

Histologic and ultrastructural features of the ichthyotic skin in X-linked dominant chondrodysplasia punctata

The ichthyotic skin in X-linked dominant chondrodysplasia punctata was investigated in a four-week-old baby and a fourteen-year-old girl. Histologically, the ichthyosiform erythroderma of the newborn and the ichthyosis of the older child presented as a retention hyperkeratosis with several distinctive features such as calcification of the keratotic follicular plugs, atrophy of the hair follicles and focal hyperpigmentation of the basal keratinocytes. On ultrastructural examination, small to medium sized vacuoles were regularly seen in the thinned granular layer. Some of these vacuoles contained needle-like calcium inclusions. The histologic and ultrastructural findings are therefore characteristic for this rare type of ichthyosis.     

Clearance of ichthyosis linearis circumflexa with balneophototherapy.

We report a 13-year-old boy suffering from severe ichthyosis linearis circumflexa. Evidence of hair shaft abnormalities and impaired immunity could not be found. The patient was treated with salt water baths and artificial UVB radiation (balneophototherapy) 3-5 times weekly. After 40 treatments with balneophototherapy the skin lesions were almost completely cleared and maintenance UVB monotherapy was performed twice weekly for 2 months. After 4 months, however, the disease relapsed. Balneophototherapy presents a potentially effective and well tolerated phototherapeutic option for ichthyosis linearis circumflexa. As only short periods of remission may be expected, intermittent balneophototherapy would be probably necessary to control the disease.     

Cholesterol sulphate levels in the hair and nails of patients with recessive X-linked ichthyosis

Cholesterol sulphate (CS) has been suggested as an intercellular glue for corneocyte-corneocyte cohesion from studies on patients with recessive X-linked ichthyosis (RXLI). Pathological stratum corneum of RXLI patients was found to show a significant elevation of CS. In the present study hair and nails, unaffected keratinized tissues in RXLI patients, were examined for CS levels. The results demonstrated significantly elevated CS levels in both tissues in RXLI patients (P less than 0.001). In particular the mean CS level in the hair of RXLI patients was five times greater than normal. The present study suggests that hair is a useful material for the diagnosis of RXLI.     

Ocular findings and skin histology in a group of patients with X-linked ichthyosis

We carried out ophthalmological examinations, and histopathological examinations of skin biopsies in 32 male patients affected by X-linked ichthyosis. We found corneal opacities in only five patients, and their presence was not related to the age of the patients. Skin histology revealed a reduction of the granular layer in nine cases, a finding previously thought to be typical of autosomal dominant ichthyosis vulgaris.