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Genetic diseases with hyper- and hypotrichosis are very heterogeneous, both clinically and genetically. This is especially true for ectodermal dysplasias but also for hereditary syndromes in which, beyond abnormal hair growth, other structures and organs are affected. In this review, we discuss distinct diseases with excessive and reduced hair growth, focusing on the clinical hallmarks and underlying genetic defects.

Hintergrund: Beim Erkrankungsbild der Aplasia cutis congenita handelt es sich um eine seltene kongenital bedingte Anlagestorung der Haut. Diese manifestiert sich zumeist an der Kopfhaut, jedoch konnen auch tiefer liegende Gewebsschichten wie Knochen oder Dura mater betroffen sein. Blutungen aus dem Sinus sagittalis sowie Infektionen stellen die haufigsten Komplikationen dar. Es existieren zahlreiche Fallberichte, jedoch besteht bisher kein eindeutiger Konsens uber das therapeutische Management, welches sowohl konservative als auch chirurgische Masnahmen beinhaltet. Methoden: Wir berichten uber 3 Neugeborene mit Aplasia cutis congenita mit isolierter Hautmanifestation ohne Beteiligung tieferliegender Gewebsschichten. In allen 3 Fallen wurden die Patienten konservativ mit Fettgaze als Wundauflage behandelt und engmaschig kontrolliert. Ergebnisse: Bei allen 3 Neugeborenen konnte innerhalb weniger Monate eine komplikationslose Abheilung samtlicher Hautdefekte erzielt werden. Schlussfolgerungen: Die konservative Therapie mit Fettgaze stellt eine verlassliche therapeutische Option bei isolierter Hautmanifestation dar.

Cutis verticis gyrata (CVG) describes a rare thickening and folding of the scalp resembling the outer surface of the brain. Secondary CVG is caused by a variety of diseases such as nevi. A 38-year-old woman presented with a long history of a deformed right parietofrontal scalp. Clinical and histopathologic criteria lead to the diagnosis of CVG secondary to a combined blue and congenital nevus. Reports of malignant melanoma developing in this clinical setting mean that each patient must be followed closely or considered for prophylactic excision.

Hay-Wells syndrome is a rare form of ectodermal dysplasia, also known as AEC syndrome (Ankyloblepharon filiforme adnatum, Ectodermal effects, Cleft lip/palate). It is inherited in an autosomal dominant fashion with variable expression, featuring congenital abnormalities of skin, hair, teeth, nail, eccrine and mucous glands. We present a three-month-old boy, born to unaffected parents, with typical clinical findings of AEC syndrome. In this boy, a mutation Ile537Thr (c.1610C>T) in the sterile alpha motive (SAM) domain of the TP73L (p63) gene was detected. Because of the broad spectrum of related syndromes such as Rapp-Hodgkin syndrome, Bowen-Armstrong syndrome, CHAND syndrome and epidermolysis bullosa hereditaria, the diagnosis of AEC should be base don both clinical findings and genetic analysis.

Ectodermal dysplasia is an inherited disease caus ing malformations of all tissues originating from the ectoderm. The significance of this disease lies in severe hypodontia, and an accompanying hypoplasia of the alveolar process. The clinical situation is aggravated by a significant xerostomia. It was the aim of this study to document the distribution of hypodontia and tooth malformation. Furthermore, we aimed to elucidate the clinical impact of these findings. Records of 30 patients (19 males, 11 females) suffering from ectodermal dysplasia were included. Their age ranged between 7 and 23 years. All patients had been examined clinically and radiographically. In every patient, a record was made of which teeth were missing or malformed, and which deciduous teeth persisted. Additionally, the entire treatment procedure was assessed. The third molars were missing in all of the patients. The number of aplastic permanent teeth ranged from 2 to 26. The maxillary lateral incisors were most frequently absent, followed by the mandibular central incisors. The most stable teeth were the central incisors of the upper jaw, and the canines and first molars in both jaws. However, the maxillary central incisors and canines were the teeth most affected by malformation. Deciduous canines and second molars were the most often persisting teeth due to agenesis of the maxillary lateral permanent incisors and mandibular second premolars. In two-thirds of the patients, missing teeth were replaced by removable dentures. Half of the patients received orthodontic treatment. Hypodontia and malformation are almost regular dental characteristics in patients suffering from ectodermal dysplasia. The distribution of absent teeth deviates remarkably from the general population. Treatment requires an interdisciplinary approach including orthodontics, prosthodontics and oral surgery.

Early-modern drawings of malformations are much less known than the woodcuts and etchings of deformed children reproduced and discussed on leaflets or in monographs. The present article publishes for the first time a drawing from 1682 showing the front and rear view of a deformed boy born in Rossla (modern Sachsen-Anhalt). These illustrations and two surviving written testimonia reveal very different attitudes to the malformed child on the part of the various individuals involved. Although the information in the sources is not sufficiently precise to allow an unequivocal retrospective medical diagnosis of the malformations, two possible interpretations are presented.

The oral and dental rehabilitation of patients with ectodermal dysplasia is a demanding and complex process. Close cooperation of medical and dental specialists is is mandatory. The individual age related situation and aspects of social integration have to be considered, when doing treatment planning for these patients. A major problem is the highly reduced number of teeth, the impaired development of the jaws and the dysplastic alteration of the teeth. The prosthodontic rehabilitation of a young girl with the congenital disease of ectodermal dysplasia is presented and discussed.

We report on a child with pili trianguli et canaliculi. This hair shaft abnormality belongs to a heterogeneous group of diseases which are included under the synonym uncombable hair. The diagnosis was confirmed by scanning electron microscopy, revealing hair shafts with a characteristic longitudinal groove. In addition the girl suffered from atopic eczema and tooth anomalies. Our findings suggest that this disorder could represent a tricho-odontal subtype of ectodermal dysplasia.

Pachyonychia congenita (PC) is a rare ectodermal dysplasia with variable expression. The condition is usually inherited as an autosomal dominant trait. Several classifications of PC have been proposed. Feinstein and colleagues suggested four clinical types of PC. Type II, the Jackson-Lawler-Syndrome, is characterized by multiple epidermal cysts, palmoplantar bullae and hyperhidrosis as well as natal teeth in addition to the main findings of pachyonychia, palmoplantar hyperkeratosis and follicular keratosis. We report two patients (father and son) with Jackson-Lawler-Syndrome and describe in detail pathogenesis, diagnostic criteria and treatment approaches as well as the different classifications of pachyonychia congenita.

We report a now three year old male patient with ectodermal dysplasia and a polysaccharide specific humoral immunodeficiency. Immunological investigations showed compromised production of IgA, IgM, and IgG2. Isohaemagglutinins still were not detectable at the age of three years. Repeated vaccination with polyvalent pneumococcal polysaccharide vaccine did not result in production of specific antibodies. Two brothers showed clinical signs of ectodermal dysplasia. The elder brother died from pneumococcal sepsis at the age of 3 years. The younger brother suffers from chronic inflammatory gastrointestinal disease with ulcerations in all parts of the gastrointestinal system. Thus, a possible association between polysaccharide specific humoral immunodeficiency and ectodermal dysplasia may be considered.

Restrictive dermopathy is a rare, fatal, autosomal recessive, congenital skin disease. Rigidity of translucent thin skin, which is thus highly vulnerable and tears, spontaneously causes intra-uterine fetal akinesia or hypokinesia deformation sequence (FADS), characteristic dysmorphic facies with fixed open mouth in O position, and generalized joint contractures (arthrogryposis). Polyhydramnios and pulmonary hypoplasia are distinctive manifestations, leading to respiratory insufficiency and premature delivery at about 31 weeks of gestation. We report on a case of a prematurely born infant who presented with the typical morphological features and describe the light- and electron-microscopical findings as described in the literature.

Pachyonychia congenita (PC) comprises a heterogeneous group of autosomal dominantly inherited conditions showing characteristic nail thickening and associated signs such as palmoplantar keratoderma, follicular keratoses, and mucosal leukokeratoses. Less frequently epidermal cysts, hairshaft abnormalities, natal teeth and laryngeal involvement may be seen. Phenotypically and genetically two major forms of PC are recognized, pachyonychia congenita Jadassohn-Lewandowsky/PC type I (Medelian inheritance in man-MIM-167200) and pachyonychia congenita Jackson-Lawler/PC type II (MIM 167210). Both conditions show nail deformities, focal palmoplantar keratoderma, and follicular hyperkeratoses. Diagnostically relevant are leukokeratoses of the oral mucosa in patients with PC type I. In contrast individuals affected with PC type II show premature dentition and multiple pilosebaceous cysts predominantly affecting the upper trunk. The latter closely resemble eruptive vellus hair cysts and steatocystoma multiplex. By mutational analysis keratin K6a and K16 gene mutations have been detected in patients with PC type I, and keratin K6b and K17 gene mutations have been shown to be the underlying genetic defect in patients with PC type II.

Pachyonychia congenita is considered to be a genodermatosis of autosomal inheritance. It is characterized by nail hypertrophy, shortly present after birth. Later on follicular keratosis of the extremities and hyperkeratosis of palms and soles can be found.We report a child with pachyonychia congenita type-I (Jadassohn-Lewandowsky). Shortly after birth nail hypertrophy of all finger- and toenails and leukoplakia of the palate and tongue were found. At the age of 3 years follicular keratosis of the extremities and plantar bullae could be found additionally.The underlying disturbance is a mutation within genes for keratin 6, 16 and 17 which leads to formation of abnormal tonofilaments. In adult patients retinoids can be used for symptomatic treatment especially of the palmoplantar keratosis.

Background Our knowledge about the pathogenesis of hereditary macular diseases is still very circumscript. For genetic determination, a knowledge of the coincidence of eye symptoms and other defined common symptoms is helpful. The purpose of this paper was to present two sisters of a family of consanguineous parents with the combination of hypotrichosis of the head and macular dystrophy in the context of a tricho-ocular malformation of an ectodermal dysplasia. A review of the recent literature is included. Patients and methods Two 13- and 17-year-old sisters presented at our hospital with reduced visual acuity because of symmetrical central changes of the retinal pigment epithelium and chorioatrophic scars according to macular dystrophy combined with hypotrichosis capitis. We performed fundus perimetry and histological examinations of the hair. Results The 13-year-old patient exhibited central changes of the retinal pigment epithelium leading to a relative central scotoma for Goldmann 1/4 during fundus perimetry in both eyes (visual acuity 0.125 and 0.4). We found central chorioatrophic scars, followed by absolute central scotomas, with unstable fixation in the upper retinal hemisphere in her 17-year-old sister with reduced visual acuity (0.16 and 0.2). Conclusion There are few descriptions of the association of macular dystrophy and hypotrichosis. The combination of hypotrichosis and macular dystrophy could make genetical analysis easier. Mutational analysis of the TIMP-3 gene that has previously been associated with Sorsby fundus dystrophy did not reveal any disease-causing mutations in our patients.

The Clarke-Howel-Evans-McConnell syndrome is a rare hereditary disease characterized by palmoplantar keratoses, squamous cell carcinoma of the esophagus and oral leukoplakia. According to a new classification recently proposed by Stevens and colleagues, the syndrome can also be classified as palmoplantar ectodermal dysplasia type III. We report a family from the Black Forest region of Germany afflicted with the syndrome. The family was traced through five generation. 27 of 46 family members showed tylotic skin changes. In addition, 8 patients showed oral leukoplakia and 5 died from squamous cell carcinoma of the esophagus. Using screening examinations, early changes of the esophageal mucosa could be detected. The responsible gene has been mapped in the family. It is located at 17q23-qter, telomeric to the keratin II gene cluster. Therefore a defect in one of the well known keratin genes can be excluded as a cause of the syndrome.

The Schimmelpenning-Feuerstein-Mims-syndrome includes deformities and dysplasias of the skin, eyes, brain, skeleton, and heart. It may result from a malformation of the ectodermal and mesodermal blastoderm in the third week of gestation. We here report on 6 patients who presented between 1977 and 1993 in comparison with those cases in the literature. All children presented neurologic symptoms. The major symptom was a linear epidermal nevus. In addition we found mental retardation, convulsions, asymmetries of the cranial structures or dilated cerebral ventricles ipsilateral to the nevus. One child had a defect of the skull and scalp, a symptom not previously mentioned in the literature. Our patients exhibited a wide phenotypice spectrum ranging from mild to severe forms. Severe neurological symptoms were also found in patients despite minimal dermal involvement.

We report on a 23-year-old man with hidrotic ectodermal dysplasia of the Clouston type showing a severe expression of his gene defect. As a prominent feature of this case, we describe the presence of verruciform keratoderma of hands and feet, and we visualize these skin changes by means of a new imprinting technique.

The present study was to examine the radiographic and histologic correlation of the respective ultrasonographic findings.Histologic examinations were performed in 12 fetuses who had died in utero between 16 and 34 weeks of gestation. The fetuses had been examined by intrauterine sonography for tooth germs and had been subjected to additional radiographic examinations post abortum or partum. During autopsy, the tooth germs were again examined sonographically and radiographically, and non-decalcified histological sections were obtained by means of the sawing and grinding technique.The results obtained by histologically examining the 12 fetal jaws in the ultrasonic plane corresponded in all cases to those examined by sonography and radiology.Sonographic proof of tooth germs might gain increasing importance in future because agenesia of tooth germs is one of the principal signs of a variety of hereditary syndromes, particularly those of ectodermal origin.

The Mulvihill-Smith syndrome consists of a large number of stigmata. A few of them are also seen in the LEOPARD syndrome. In both syndromes keratoconus has not yet been reported.We present a twenty-year-old male patient suffering from keratoconus in connection with a Mulvihill-Smith syndrome. A keratoplasty à chaud was done after perforation of the corneal ulcer.As a major complication corneal graft rejection is known after keratoplasty à chaud. However, in our patient immunological graft failure may be prevented by the T-cell defect.

Uncombable hair is a heterogeneous symptom with a partially genetic background. In order to make an exact diagnosis, it is mandatory to recognize associated abnormalities, do pedigree analyses, and perform scanning electron microscopic studies of the hair. In a case of ectodermal dysplasia, ectrodactyly, cleft lip/palate (EEC) syndrome and in a patient with familial tricho-odonto-onychial ectodermal dysplasia with syndactyly, scanning electron microscopy demonstrated pili torti et canaliculi, helicotrichia and cuticular dystrophy. Congenital pili torti et canaliculi must be differentiated from pili torti and from pili trianguli et canaliculi ("cheveux incoiffables"), inasmuch as they may present in hypotrichosis congenita hereditaria of Marie-Unna or as part of complex ectodermal dysplasia syndromes with clefting of the lip/palate and/or limb defects. It is noteworthy that some of those patients show a dysmorphic facies and an atopic constitution in addition to the aforementioned abnormalities. We discuss the possible relationship of these syndromes to each other, with special respect to the Hay-Wells or ankyloblepharon, ectodermal dysplasia, cleft lip/palate (AEC) and the Rapp-Hodgkin (ectodermal dysplasia, midfacial hypoplasia, cleft lip/palate) syndromes.

We report on an 11-year-old female patient with anhidrotic ectodermal dysplasia (AED) showing the following characteristics: (1) reduced number of hair follicles and incomplete formation of sweat glands; (2) disturbed hair growth with shortening of anagen and anhidrosis; (3) disturbed cytokeratin expression pattern of CK 13, 14, 19 (follicular epithelium) and of CK 18 (eccrine sweat glands); (4) reduction of cystine and increase in sulphonic cysteine acid. Thus, we demonstrated pathological differentiation on the immunomorphological and on the biochemical level, leading to disturbed keratinization that could be visualized by transmission and scanning electron microscopical studies of the hair shafts. According to these findings AED is a developmental defect that involves not only incomplete formation of hair follicles and sweat glands but also a disordered differentiation and follicular keratinization with disturbed cytokeratin pattern and pathological amino acid composition of the terminal hairs produced.

The nails are often involved in complex dysplasias. The present paper reviews nail manifestations of complex dysplasias, ectrodactylia and selected palmoplantar keratoses with associated symptoms. Some of these are of early diagnostic importance, while others are rare symptoms of complex dysplasias. Mono- and oligosymptomatic syndromes are drawn to the reader's attention.

Schöpf syndrome is an unusual genodermatosis categorized within the heterogeneous group of ectodermal dysplasias. Since the first description of this syndrome in 1971, ten further cases have been published. The diagnostic features include eyelid cysts, hypotrichosis, hypodontia, nail dystrophy, and keratosis of palms and soles. When the signs and symptoms noted in all published cases are taken together, considerable clinical variability in the combinations and in the age of onset is observed. The frequent occurrence of benign and malignant tumours of the palms and soles deserves particular attention. Schöpf syndrome is probably not as rare as is commonly believed. A woman with typical clinical features of this syndrome is presented. Schöpf syndrome is assumed to be passed on as an autosomal recessive trait; however the present and two further case reports are not compatible with this mode of inheritance, because family members in several generations are affected. Schöpf syndrome is probably a heterogeneous disorder. Lipid biochemical investigations of stratum corneum by high-performance thin-layer chromatography (HPTLC) show a decrease in the ceramide fraction and an increase in free fatty acids as a percentage of total lipids. The pathophysiological significance of these findings needs further investigation.

Fever--the most frequent symptom of diseases in children--points diagnostically to an infection. We report on a child who presented with recurrent high fever of unknown origin. Infectious diseases could be excluded. During a general medical checkup the results of repeated pilocarpine iontophoresis attracted attention by the minimal secretion of sweat. The diagnosis of hypohydrotic ectodermal dysplasia could be confirmed by dermal biopsy since all integumentary appendages were missing. Only 300 cases of this rare hereditary dysplasia can be found in the literature.

Fever of unknown origin, unability to sweat, hypotrichosis, absent eyebrows and thick everted lips were symptoms in a 3 month old female infant and raised the suspicion of anhidrotic ectodermal dysplasia. After several days of high fever and enteritis our patient presented with convulsions which could hardly be interrupted for a couple of days. Two months later brain scanning revealed serious brain damage. Finally the diagnosis of anhidrotic ectodermal dysplasia was confirmed by the unability to sweat by means of the quantitative pilocarpin iontophoresis test. Skin biopsy showed absence of the eccrine glands.

We report on a 23-year-old women suffering from a hidrotic ectodermal dysplasia with baldness, xerodermia, kyphosis of the chest, hypopigmented mamillae, disturbances of the menstrual cycle, dysphonia and keratitis punctata superficialis recidivans. The complex condition is classified as a tricho-oculo-dermo-vertebral syndrome. Immunohistological findings suggest a combined alteration of epithelial differentiation of hair follicles and interfollicular epidermis.

Anal sphincter dysplasia is a congenital, often familial malformation of the anal canal. In the literature, the anomaly is poorly represented and usually referred to as anteriorly or ventrally displaced anus. The range of symptoms includes chronic constipation, severe straining at defecation, encopresis and chronic paradoxical diarrhea with fecal incontinence. One usually finds dysplasia and absent (type I) or incomplete (type II) fixation of the sphincter complex to the coccyx. Both are demonstrable by computerized tomography (CT) as well as by intraoperative dissection of the sphincter muscles. There ist also shortening of the ectodermal segment of the anal canal which is obviously responsible for the disturbed stool sensation. Posterior butterfly anoplasty combined with fixation of the sphincter complex to the coccyx usually leads to immediate improvement of defecation disorders. A genetic study on 42 patients (age 1-52 years) operated on for anal sphincter dysplasia revealed autosomal dominant inheritance with variable expression and probably incomplete penetrance of the mutated gene.

We report on a 46-year-old man with X-linked hypohidrotic ectodermal dysplasia, who presented with large skin areas covered with aggregated sebaceous gland papules on the face and neck. This is rare, but has been observed in very similar form in association with this disorder in a not insubstantial proportion of cases.

A 15-year-old boy had suffered burning of both palms and all fingers during his 2nd year of life. Epitheliazation of the lesions did not occur. In his 6th year, erythema, desquamation and erosion-like alterations appeared spontaneously on the soles of both feet and on the plantar sides of the toes. These alterations were similar to those on the hands. Histologically the lesion on the right sole was covered with a very thin horny layer and thin epidermis. The cells of the epidermis had clear cytoplasm and probably derived from the ductal epithelium of the sweat glands. Under the atrophic epidermis, granulation tissue consisting of lymphocytes, plasma cells, histiocytes, and a few polynuclear cells and eosinophils was seen. The following symptoms were still present in the boy: dys- and hypotrichosis, oligodontia, enamel and dentin hypoplasia, cleft palate and uvula, concomitants strabismus (left eye), and cryptorchidism. Transplantation of the patient's skin from the right thigh to the lesion on the right sole was tried. The authors postulate a previously unreported form of ecto-mesodermal dysplasia in this case.

A profound knowledge of specific genetically determined anomalies of the hair may be of considerable value in the diagnosis of genetic syndromes. We give a review of a few recent developments in the field of genetic hair diseases. For example, the brittle hair due to sulphur deficiency (trichothiodystrophy) is nowadays regarded as genetically heterogeneous; three different syndromes can be distinguished: BIDS syndrome, Tay syndrome, and PIBIDS syndrome. Polarization microscopy revealed a striking resemblance of the hair anomalies found in trichothiodystrophy syndromes and those in acrodermatitis enteropathica. This surprising result indicates similar pathophysiological mechanisms. The Comèl-Netherton syndrome--long regarded as representing two different diseases--has recently been recognized as a clinically variable, but genetically homogeneous syndrome, which is most likely based on a single mutation ("lumping"). Minor's sweat test allows the recognition of women heterozygous for X-linked hypohidrotic ectodermal dysplasia and may help to appreciate seemingly non-specific hair findings, such as diffuse alopecia.

4 families suffering from hidrotic ectodermal dysplasia (HED) are reported. They belong to the tricho-onychotic subgroup, type Clouston. The trichologic investigations showed a disturbance of the cuticular pattern, being a constant feature of this HED-subgroup.