Loss-of-Function Mutations in SERPINB8 Linked to Exfoliative Ichthyosis with Impaired Mechanical Stability of Intercellular Adhesions.

SERPINS comprise a large and functionally diverse family of serine protease inhibitors. Here, we report three unrelated families with loss-of-function mutations in SERPINB8 in association with an autosomal-recessive form of exfoliative ichthyosis. Whole-exome sequencing of affected individuals from a consanguineous Tunisian family and a large Israeli family revealed a homozygous frameshift mutation, c.947delA (p.Lys316Serfs(∗)90), and a nonsense mutation, c.850C>T (p.Arg284(∗)), respectively. These two mutations are located in the last exon of SERPINB8 and, hence, would not be expected to lead to nonsense-mediated decay of the mRNA; nonetheless, both mutations are predicted to lead to loss of the reactive site loop of SERPINB8, which is crucial for forming the SERPINB8-protease complex. Using Sanger sequencing, a homozygous missense mutation, c.2T>C (p.Met1?), predicted to result in an N-terminal truncated protein, was identified in an additional family from UAE. Histological analysis of a skin biopsy from an individual homozygous for the variant p.Arg284(∗) showed disadhesion of keratinocytes in the lower epidermal layers plus decreased SERPINB8 levels compared to control. In vitro studies utilizing siRNA-mediated knockdown of SERPINB8 in keratinocytes demonstrated that in the absence of the protein, there is a cell-cell adhesion defect, particularly when cells are subjected to mechanical stress. In addition, immunoblotting and immunostaining revealed an upregulation of desmosomal proteins. In conclusion, we report mutations in SERPINB8 that are associated with exfoliative ichthyosis and provide evidence that SERPINB8 contributes to the mechanical stability of intercellular adhesions in the epidermis.

Atopic dermatitis and mother-child interaction: a comparative study of 48 dyads.

BACKGROUND: Psychological factors and family environment may play a role in the pathogenesis and the persistence of atopic dermatitis (AD). AIM: To evaluate the interactions between mothers and their children suffering from AD and to look for the presence of maternal depression and anxiety. METHODS: A sample of 24 children with AD and their mothers and 24 matched control dyads participated in the study. Maternal depression and anxiety were assessed using the Beck Depression Inventory-short form (BDI) and the Hamilton Anxiety Rating Scale (HAM-A). The mother-child interaction was evaluated by video recording, and through scores established after analyses of the video: M-score for the mother's attitude towards the child and C-score for the child's behavior. RESULTS: AD group mothers showed significantly higher scores on the HAM-A,but not on the BDI. The analysis of the video recording conveyed a significant difference in M-scores between the two groups but no difference in C-scores.. M-score was correlated with the mother's anxiety. CONCLUSION: Our study found evidence in favor of a disturbance of the mother- child interaction in the case of AD, noted on the mother's side, and more anxiety in AD group mothers than in the control group. Our findings suggest the need for psychological support for mothers of children suffering from AD.

Identification of SLC39A4, a gene involved in acrodermatitis enteropathica.

We have characterized the human gene SLC39A4, which encodes a protein with features characteristic of a ZIP zinc transporter. The chromosomal location and expression of SLC39A4, together with mutational analysis of eight families affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally involved in the pathogenesis of this condition.

Pseudotumoral cutaneous aspergillosis in chronic granulomatous disease, report of a pediatric case.

Invasive aspergillosis is a life-threatening condition in patients with chronic granulomatous disease (CGD). Skin invasion by Aspergillus occurs most commonly by contiguity to a neighboring cavity. We describe an unusual case of invasive cutaneous aspergillosis presented as a large burgeoning tumor in a 4-year-old girl with CGD who underwent surgical treatment for bifocal osteomyelitis of the left leg. The skin invasion occurred 4 months after a "successful" treatment of invasive pulmonary aspergillosis. Atypical presentation and diagnostic difficulties are discussed. Invasive cutaneous aspergillosis may be polymorphic. The diagnosis should be considered early in the etiological investigation of any suspicious skin lesions in CGD even in uncommon aspects such as burgeoning tumors.

Postvaccination morphea profunda in a child.

We report a new case of postvaccination morphea profunda (MP) in a child and discuss its different clinical presentations, prognosis, and therapy and its relationship with "solitary morphea profunda." A 2-year-old healthy girl presented with an induration of the anterior aspect of the left thigh of 9 months duration. The lesion had appeared 3 months after a third dose of diphtheria-tetanus-pertussis vaccine. Cutaneous examination showed an induration of 7 × 7 cm with an "orange peel" texture after pinching the skin. Histologic examination confirmed the diagnosis of MP. Systemic steroids (1 mg/kg/day) led to the stabilization of the lesion. After 4 months of treatment, we began the concomitant use of oral methotrexate (10 mg/wk) for 2 months. Methotrexate was then continued alone for 10 months, leading to a significant regression of the induration with no relapse.

[Not Available]. / Traitement du psoriasis par méthotrexate à l'ère des biothérapies : étude chez 21 patients tunisiens.

INTRODUCTION: We present here results of methotrexate, in term of efficacy and tolerance, administrated in 21 Tunisian patients with severe psoriasis. METHODS: It was a retrospective study conducted between january 2002 and december 2009 in the department of dermatology of Charles Nicolle Hospital of Tunis. We have included 21 patients with severe psoriasis treated by methotrexate. RESULTS: Patients were 53year-middle aged with a sex-ratio=6. Psoriasis evolved for a mean of 10years (1month-60years). Patients had: plaque psoriasis (n=18, 85.8%) with 63% body surface involvement, erythrodermic psoriasis (n=2, 9.5%) and psoriatic arthritis (n=1, 4.7%). Methotrexate was orally administrated at an initial dose of 5-7.5mg/week. The maximum dose was of 7.5mg-12.5mg/week. Complete remission was achieved in 62% of cases and partial remission in 28.5% of cases. Haematological and hepatic toxicities were observed in 2 patients (9.5%). Mean remission period was of 14months (3months-3years). Seven patients had severe relapses. CONCLUSION: Our study concluded to the efficacy of methotrexate in severe psoriasis with a high rate and long term remission, despite lower doses than those classically used in the literature.

[Treatment of psoriasis by methotrexate in the era of biotherapies: a study in 21 Tunisian patients]. / Traitement du psoriasis par méthotrexate à l'ère des biothérapies : étude chez 21 patients tunisiens.

INTRODUCTION: We present here results of methotrexate, in term of efficacy and tolerance, administrated in 21 Tunisian patients with severe psoriasis. METHODS: It was a retrospective study conducted between january 2002 and december 2009 in the department of dermatology of Charles Nicolle Hospital of Tunis. We have included 21 patients with severe psoriasis treated by methotrexate. RESULTS: Patients were 53 year-middle aged with a sex-ratio = 6. Psoriasis evolved for a mean of 10 years (1month-60 years). Patients had: plaque psoriasis (n = 18, 85.8%) with 63% body surface involvement, erythrodermic psoriasis (n = 2, 9.5%) and psoriatic arthritis (n = 1, 4.7%). Methotrexate was orally administrated at an initial dose of 5-7.5 mg/week. The maximum dose was of 7.5 mg-12.5 mg/week. Complete remission was achieved in 62% of cases and partial remission in 28.5% of cases. Haematological and hepatic toxicities were observed in 2 patients (9.5%). Mean remission period was of 14 months (3 months-3 years). Seven patients had severe relapses. CONCLUSION: Our study concluded to the efficacy of methotrexate in severe psoriasis with a high rate and long term remission, despite lower doses than those classically used in the literature.

Cutaneous adverse drug reactions in children. A series of 90 cases.

BACKGROUND: Cutaneous adverse drug reactions (CADR) are frequent in children. They have different clinical presentations and may be caused by several drugs. AIM: To evaluate the epidemioclinical features of cutaneous adverse drug reactions (CADR) and the different causative drugs in a Tunisian paediatric series. METHODS: We have retrospectively included 90 children (under 16 years old) with a well documented cutaneous drug reaction, seen in the Department of Dermatology of Charles Nicolle hospital of Tunis over 18 years (1991-2008). Age, gender, duration of skin disorders, type of cutaneous lesions, incriminated drugs, delay between drug consumption and eruption, validation by the national pharmacovigilance centre, treatment and outcome were recorded. RESULTS: Our patients were 6.9 year-aged (sex-ratio M/F 1.19). They had maculopapular eruption (MPE) (57.7%), acute urticaria (16.6%), fixed drug eruption (14.4%), erythema multiform (2.2%), photosensitization (1.1%) or severe cutaneous drug reactions (10%).Incriminated drugs were: Antibiotics (55.5%), non-steroidal antiinflammatory drugs (18.8%), antiepileptics (11.1%), and analgesics (5.5%). Betalactamins were the most commonly incriminated antibiotics (32 out of 50 patients; 64%). Barbiturates were the most commonly incriminated anti-epileptics (7/90 cases, 7.7%). Favourable outcome was noted in all patients, even those with severe drug reactions. CONCLUSION: MPE to antibiotics were the most common kinds of CADR in children. Drug responsibility should be based on solid criteria given the frequency of MPE of infectious origin and the frequent prescription of antibiotics in paediatric population.

[Kindler syndrome: clinical and ultra-structural particularities, a propos of three cases]. / Le syndrome de Kindler, particularités cliniques et ultrastucturales à travers trois nouvelles observations familiales.

INTRODUCTION: Kindler's syndrome is a rare type of genetic skin condition belonging to the class of bullous poikilodermia. We report three new sibling cases of this rare syndrome. CASES REPORTS: The condition was seen in three sisters aged 12, 16 and 20 years, born of a first-degree consanguineous marriage with no family history of Kindler's syndrome. The three patients presented spontaneously regressive bullous eruptions, poikilodermia of gradual onset, major cutaneous atrophy on the back of the hands and the feet, photosensitivity and gingival hypertrophy. Electron microscopy examination of poikilodermic skin showed normal anchoring filaments and intraepidermal cleavage. DISCUSSION: Diagnosis of Kindler's syndrome is based upon clinical evidence. Kidler's syndrome is a well defined clinical entity. Ultra-structural studies show intraepidermal, junctional, and dermal cleavage. This syndrome must be differentiated from congenital epidermolysis bullosa, Weary's syndrome, and other bullous hereditary poikilodermas.

Early onset childhood cicatricial pemphigoid: a case report and review of the literature.

Cicatricial pemphigoid is an extremely rare condition in children, since only 17 cases have been reported in the English literature, so far. We describe a new case in a 20-month-old boy, who is to our knowledge the youngest patient reported yet. The disorder had begun 10 months before he was referred to our department by mucosal crusted erosions of the oral and nasal cavities and conjunctivae. Cutaneous examination showed buccal erosions with limited mouth opening, entropion of the lower eyelids, trichiasis, cicatricial cornea, synechia of the nasal cavities and hypopigmented lesions of the abdomen. There were no anal or genital lesions. Cicatricial pemphigoid was confirmed by positive direct and indirect immunofluorescence on mucous biopsy. Systemic corticosteroids (2 mg/kg/day), maintained for 12 months, had led to complete healing of lesions. But due to cicatrization, synechia of the nasal cavities and corneal opacities, leading to a dramatic visual loss, have occurred. Dapsone 25 mg/day and topical ocular cyclosporine are now maintained to avoid relapse. Our review of the literature of all cases of CP showed that ocular and to a less degree, vulvar lesions are the most severe ones, due to the serious complications with scar formation.

Linear IgA bullous dermatosis: the more frequent bullous dermatosis of children.

BACKGROUND: Linear IgA bullous dermatosis (LAD) of children is relatively frequent in Africa. We undertook this study to evaluate the frequency of this disease among autoimmune bullous diseases (AIBD) in Tunisian children. METHODS: We present a 32-year retrospective study (January 1976 to December 2007). Children with chronic acquired bullous diseases seen at the Charles Nicolle Hospital of Tunis and for whom direct immunofluorescence (DIF) of the perilesional skin demonstrated linear IgA immunoglobulin deposits were included in the study population. RESULTS: Thirty-one children with LAD were collected representing 65.9 percent of all AIBD of children collected in the same period, with a mean age of 5.5 years and a sex ratio M/F of 2.4. Most of the children had a generalized eruption (28/31) but more profuse on the face, pelvic region, buttocks, and limbs. Mucosal lesions were present in only 4 children (12.9%). The mean duration of the disease was 14 months. Direct immunofluorescence demonstrated predominantly linear IgA deposits along the dermal-epidermal junction in all patients. Faint IgG, IgM, and complement were also seen (20/31). Indirect immunofluorescence was negative in 67 percent of cases. Eight patients responded to Dapsone, but prednisone had to be added in 7 children and erythromycin in 4 others to control the disease. A long term remission period (34 months) was achieved in 61.9 percent of patients. CONCLUSION: This study confirms that LAD is the most common AIBD in children in Tunisia and it frequently occurs in preschool-aged males. Independently of the medication chosen for treatment, a long term remission is frequently observed.

Generalized peeling skin syndrome: Case report and review of the literature.

Peeling skin syndrome (PSS) is a rare form of ichthyosis with a probable autosomal recessive inheritance that exhibits superficial, painless, continual, or seasonal cutaneous exfoliation. The syndrome generally appears at birth or in infancy. We report a case of generalized PSS and provide a literature review. A 34-year-old woman reported a lifelong history of generalized and painless peeling of the skin that worsened in summer. Her parents were third degree cousins. Her twin sister and her two cousins presented with the same condition. Physical examination showed widespread superficial sheets of variable size that could be easily removed without bleeding or pain. No underlying erythema was noted. Otherwise, the patient was in good health. Histological findings showed an epidermal cleavage within the stratum corneum. The generalized form of PSS is classified into 3 types, A, B, and C, according to the classification system of Traupe and Mevorah. We have tried to classify the cases of generalized PSS already reported in the literature into one of these three types. Thirteen reported cases probably presented PSS-type A. Sixteen patients are best described as PSS-type B. Two patients exhibit PSS-type C. Fifteen reported patients had an acral form of peeling skin syndrome. The classification of the eleven remaining patients was difficult to determine. Our patient presented clinical and histological features of generalized PSS-type A.

Congenital cutaneous candidiasis associated with respiratory distress in a full-term newborn.

BACKGROUND: Congenital candidiasis is rare occurring in most cases in premature and low birth weight new born. It can produce a spectrum of disease ranging from a diffuse skin eruption to a severe systemic disease with or without skin involvement. Amphotericin B is the first-line agent for the treatment of systemic disease. AIM: To describe a congenital candidiasis in a full-term newborn. CASE REPORT: At birth, the newborn had a generalized, erythematous, papulovesicular eruption. He was treated by topic antifungal therapy. However, on the third day, he developed a systemic disease with respiratory distress and fever. Ear, skin swab and gastric aspirate grew to Candida albicans. The newborn was given fluconazole for 10 days with favourable outcome. CONCLUSION: Early topic therapy did not prevent systemic spread of congenital cutaneous candidiasis in our case. Treatment with fluconazole, as the first-line agent, seems effective and safe.

[Side effects of meglumine antimoniate in cutaneous leishmaniasis: 15 cases]. / Les effets indésirables du Glucantime par voie générale, dans le traitement de la leishmaniose cutanée: à propos de 15 cas.

BACKGROUND: Leishmaniasis is wide spread parasitic disease considered to be endemic in 88 countries in both old and new world. The standard treatment remains Meglumine antimoniate. AIM: We study the side effects of systemic meglumine antimoniate in cutaneous leishmaniasis. METHODS: We conduct a retrospective study covering 3-year period (2002- 2005). All medical reports of cutaneous leishmaniasis treated by systemic Meglumine antimoniate are reviewed. RESULTS: The study comprise 63 patients all treated by systemic meglumine antimoniate at the dose of 60 mg/kg/day for 10-15 days. Side effects were noted in 15 cases (12 females and 3 males). The subject's age range from 11 to 78 years. Stibio-intolerance (fever, rash, arthralgia, abdominal pain) was observed in 12 cases and stibiotoxicity in 3 cases: precordialgies 1 case, hyperamylasemia and increase liver enzyme: 1 case, pancytopenia, renal and hepatic failure leading to death: 1 case, skin eruption: 7 cases, pruritus and erythema in the site of injection: 5 cases, urticaria: 1 case. Meglumine antimoniate was stopped in 13 cases. CONCLUSION: Meglumine antimoniate is the generally recommended treatment of cutaneous leishmaniasis. In spite of the rarity of Glucantime's side effects, we recommend a careful survey especially in older patients.

[Chronic lupus erythematosus: 104 Tunisian cases]. / Le Lupus Erythémateux Chronique: 104 cas tunisiens.

BACKGROUND: Chronic lupus erythematosus is a cutaneous form of lupus erythematosus, usually involving photoexposed areas. AIM: The aim of our study is to evaluate the epidemio-clinical trends, therapeutic features and outcome of patients with chronic lupus erythematosus, through a Tunisian hospital series. We have tried to compare our results with those of other African and western series. METHODS: It is a retrospective study, concerning all patients with chronic lupus erythematosus, attending the Dermatology department of Charles Nicolle Hospital over an 11 years period. The patients' age, sex, clinical features, explorations results, treatment and evolution were recorded. RESULTS: A total of 104 patients were included. Chronic lupus erythematosus represented 0,1 % of all the dermatitis seen over 11 years. Chronic lupus erythematosus affects young women with a ratio F/M of 1,97 and an average age of 42 years. The discoid form was the most frequent clinical shape, observed in 73 % of cases (76 patients). The face was the most frequent localization of the lesions (91%). Five patients (4.8%) presented a generalized chronic lupus erythematosus. The direct immunofluorescence in sick skin was positive in 54 % of cases. Treatment included sun avoidance and oral antimalarials drugs in the majority of cases (95%). The progression from chronic lupus erythematosus to systemic lupus erythemetosus was observed in two cases (2%). CONCLUSION: Chronic lupus erythematosus is a relatively rare disorder in Tunisia, compared to other African countries, where prevalence is 7 to 10 times more frequent. As shown in our study, the most common clinical feature is the discoid form. The diagnosis can be confirmed by histopathological and direct immunofluorescence examination. Progression of chronic lupus erythematosus to systemic lupus erythematosus is possible, as observed in two of our patients. Thus, Patients with chronic lupus erythematosus should be continually followed up.

An update on mutations of the SLC39A4 gene in acrodermatitis enteropathica.

Acrodermatitis enteropathica (AE) is a very rare inherited recessive disease caused by severe zinc deficiency. It typically occurs in early infancy and is characterized by periorificial and acral dermatitis, alopecia, and diarrhea. In 2002, both we and others identified the AE SLC39A4 gene located at 8q24.3, and described the first causative mutations for the disease. The SLC39A4 gene encodes a zinc-specific transporter belonging to the Zinc/Iron-regulated transporter-like family, which is highly expressed in the duodenum and jejunum. The SLC39A4 mutations are spread over the entire gene and include many different types of mutations. We report here the identification of five novel variants, including three likely pathogenic mutations. Since the first description, 31 mutations or unclassified variants of SLC39A4 have been reported in this gene. Although most of the patients with AE carry homozygous or compound heterozygous mutations, some of them have either no SLC39A4 mutation or only a monoallelic mutation. Thus, a genotype-phenotype correlation is not easily defined for all AE patients, and the molecular basis of the disease could be more complex than previously described. In cases unexplained by current genetic analyses, the most plausible molecular causes could be a dysregulation of the SLC39A4 gene transcription -- involving either metal response elements (MREs) or a modifier gene -- or the existence of another putative AE gene. In this review, we summarize the current knowledge of SLC39A4 mutations, as well as the future prospects to fully unravel the pathogenesis of AE.

Assessment of cryotherapy by liquid nitrogen in the treatment of hand and feet warts.

BACKGROUND: Cryotherapy with liquid nitrogen is the most widely used method to treat hand and feet warts. Therapeutic response to this method depends on many factors related to warts and to the patient. The aim of this study is to determine factors influencing therapeutic response of warts to cryotherapy by liquid nitrogen. METHODS: It was a prospective transversal study including 100 patients with warts of the hands and/or feet treated by cryotherapy with liquid nitrogen (cotton wool bud) and referred to Dermatology Department of Charles Nicolle Hospital of Tunis. Demographic data, so as characteristics of warts were recorded. Patients received one treatment/week with a maximum of 4 sessions. Patients whose warts were seen to be resolved were classified as cured. Cure-predictive factors were studied with a multi varied study with logistic regression. RESULTS: Of the 100 patients (56 females/44 males, Mean age: 22 years), ten were withdrawn. In 89 patients, warts were present on hands, whereas 23 had warts on feet and 12 had warts on both hands and feet. The mean number of warts per patient was 7. The total cure rate was of 64.4% and was more elevated in hands compared to feet (70.8% versus 10.5%). There was no difference between mean ages of cured group and not cured one (22.2 years versus 21 years). The mean duration of warts in cured patients was lower than that of not cured patients. The mean number of warts before treatment was 4.3 in cured patients and 12.3 warts in not cured patients. The mean number of treatments was 2.3 in cured patients and 4 treatments in not cured patients. The difference between these factors into cured and not cured groups was statistically significant in uni-varied study but not significant in multi-varied one. CONCLUSION: The effectiveness of liquid nitrogen used by traditional method in the treatment of hand and feet warts seems to depend on multiple factors: wart's duration, number of warts and number of treatments. These factors depend on each other.

[Orf of the hand]. / Orf de la main.

INTRODUCTION: The orf is a zoonotic infection which can be transmitted to humans. OBJECTIVE: The aim of our report is to describe this often misdiagnosed viral infection in a man with an orf of the hand appearing after the feast of the sacrifice. CASE REPORT: A 40-year-old man with no past medical history, presented with a nodular lesion on the fifth right finger evolving for 3 weeks which had appeared 2 weeks after the feast of the sacrifice. Histology showed a vacuolar degeneration of keratinocytes probably of viral origin. Both histological aspect and the contact with sheep, led to the diagnosis of hand orf. Three weeks later the lesion had spontaneously resolved. CONCLUSION: Orf is an infectious mucocutaneous disease due to a parapoxvirus. It is more frequent in professionally exposed persons (veterinary, butchers...). But, in our country, the frequency of the orf increases after the feast of the sacrifice and remains undiagnosed because patients do not consult. The diagnosis may be confirmed by electron microscopy, conventional histopathology or by isolation of the virus by PCR. Information on the benign character of the disease and reassurance of the infected patient are very important because lesion usually resolves spontaneously.

[Bullosis diabeticorum: report of ten cases]. / La bullose des diabétiques: a propos de dix cas.

BACKGROUND: Bullosis diabeticorum is a rare characteristic complication of diabetes mellitus; it affects 0.5% of diabetics. Bullosis diabeticorum is a manifestation of complicate and longstanding diabetes mellitus. THE AIM: of our study was to describe particularities of diabetes in patients suffering of this disease. METHODS: We have led a retrospective study covering a 5 year-period (January 2001 - December 2007) in the dermatology department of the Charles Nicolle's hospital in Tunisia. We selected for this study all cases of bullosis diabeticorum. RESULTS: During the studied period, 10 cases have been collected. They were in all cases about complicate and long-standing diabetes. Bullosis diabeticorum has a favourable outcome in all cases with symptomatic treatment. CONCLUSION: The different cases of bullosis diabeticorum reported in our series were associated to complicate diabetes mellitus what lets suggest that vascular deteriorations led to cutaneous fragility responsible for the skin cleavage.

[Anhidrotic/hypohidrotic ectodermal dysplasia: ten cases]. / Dysplasie ectodermique hypo/anhidrotique: 10 observations.

BACKGROUND: Ectodermal dysplasias are rare hereditary diseases characterised by congenital absence of ectodermally derived structures and classified according to four symptoms: trichodysplasia, hypodontia, onychodysplasia and hypohidrosis. AIM: The objective of our study is to precise the epidemioclinical characteristics, the diagnostic tools, the evolution and the treatments of this rare disease through a 10-case series of hypohidrotic ectodermal dysplasia (HED). METHODS: The present report is a retrospective study of all cases of an/hypohidrotic ectodermal dysplasia collected from 1977 to 2006. We have specified age, sex, parental consanguinity, similar familial cases, clinical and histological features, dental, oto-rhino-laryngologic, ophthalmologic and respiratory examinations. RESULTS: Ten cases of HED were collected (average age: 14 years, sex ratio 9/1). The mean duration diagnostic period was of 14 years. Parental consanguinity was registered in 3 cases but only one patient had similar familial cases. All patients had facial dysmorphy, hypotrichosis and hypo/anodontia (respectively 8/10 and 2/10). All patients had clinically and histologically documented hypoplastic (6/10) or aplastic sweat glands (4/10). Extra-cutaneous manifestations were noted in 8 patients (recurrent rhinitis 6/10, recurrent pneumopathies 3/10, xerophtalmy 3/10). CONCLUSION: Our series deals with 10 cases of HED, consisting in Chris-Siemens Touraine syndrome. It highlights the delayed diagnosis of this disease (mean: 14 years) with a diagnosis made at an adult age in four patients. Our study confirm the X-linked heredity (9/10) with a possible autosomal transmission (one female-case). HED is rarely life-threatening, but early diagnosis allows a better quality of life to patients and genetic counselling to parents. Our series illustrates the rarity of HED which is also probably due to its underestimation by clinicians.