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The late onset of normal keratinization after week 24 menstrual age (MA) of fetal life is the cause of considerable problems with the prenatal diagnosis of congenital ichthyosis. This paper summarizes the experiences with prenatal diagnosis in nine pregnancies at risk of congenital ichthyosis and one at risk of chondrodysplasia punctata, rhizomelic type. An important prerequisite--and the main problem--is the manifestation of the mutant genes early enough in fetal life to allow a safe exclusion. Continuous precocious keratinization of the interfollicular epidermis, hyperkeratosis, and/or specific markers of congenital ichthyosis such as various types of lipid inclusions had been expected. With a normal ultrastructure and development of fetal epidermis no evidence of ichthyosis was present in eight cases; all eight children were born healthy. Regional variations of the onset of keratinization of the interfollicular epidermis, observed in one of these eight fetuses as well as in one fetus at risk (but normal for) recessive dystrophic epidermolysis bullosa, posed considerable problems and might lead to a false-positive diagnosis. Examination after birth allowed one to localize these regions to areas close to the mamillae. Regional variations in addition to the well-known cranio-caudal gradient thus are normal findings: both children have normal skin. One fetus at risk of non-bullous congenital ichthyosiform erythroderma (type II) was involved without prenatal manifestation of interfollicular keratinization, specific markers, or increased numbers of cornified cells in the pilosebaceous follicles at 20 weeks MA. A slightly more irregular pattern of the horn cell contents was not regarded as sufficient evidence alone to indicate congenital ichthyosis. A severely affected boy was born in week 34 MA. Similarly the fetus at risk of chondrodysplasia punctata showed no skin abnormalities, neither at fetoscopy (week 22 MA) nor after abortion (week 24 MA) although based on other clinical features it was clearly affected. Thus, this genodermatosis cannot be diagnosed prenatally by its keratinization disturbances. In future cases, precocious keratinization and hyperkeratosis cannot be expected to be expressed before week 24 MA, and minor signs, such as irregularities of horn cell contents, have to be taken as an indication of involvement. Multiple biopsies are required, and a safe exclusion may be impossible before week 22 MA.

A presentation of a 3-year-old girl with a congenital hemidysplasia of the left side together with ichtyosiform erythroderma, the so-called CHILD-syndrome. A short review of the syndrome is given.

This is a report on a child with a syndrome characterized by an extensive congenital ichthyosiform eruption, neurosensory deafness and abnormally elevated serum steroid disulfates neonatally. When analysed by gas-liquid chromatography (glc) and gas chromatography-mass spectrometry (gc-ms) the following serum steroid disulfates were very high 5 days after birth: 5-androstene-3 beta,17 alpha-diol (56 micrograms/ml), 5-androstene-3 beta,17 beta-diol (25 micrograms/ml) and 5-pregnene-3 beta,20 alpha-diol (26 micrograms/ml). The values are about one hundred times higher than the reference values at this age. At the same time serum steroid monosulphate concentrations were normal. The patient had normal steroid sulfatase activity in skin biopsies, indicating that enzyme deficiency was not the reason for the high steroid disulfate concentrations. When serum steroid disulphatases were next analysed at 16 months of age they were normal. No hepatomegaly was observed but the other laboratory data support the hypothesis that the serum steroid disulphate concentrations were due to neonatal hepatography. Later, no indications of chronic liver disease were observed. These indications have not been described earlier in ichthyosiform erythrodermia and it is possible that the patient represents a new type of this rare disease.

Recently, autosomal-dominant lamellar ichthyosis (ADLI) has been shown to be a new genetic trait with clinical and histologic features similar to those of autosomal-recessive lamellar ichthyosis. In two patients affected with ADLI, the malpighian keratinocytes showed ultrastructural signs of increased cellular metabolism. The tonofilaments and keratohyaline granules were regular in structure and number. However, as a distinctive ultrastructural feature, a prominent transforming zone was found between the granular and horny layers. Moreover, a normal keratin pattern and only a limited number of lipid inclusions were observed in the stratum corneum. Thus, ADLI can be distinguished from the autosomal-recessive forms of lamellar ichthyosis, permitting a correct diagnosis when genetic counselling has to be given in sporadic cases.

A patient with congenital ichthyosis and progressive neurologic anomalies showed disturbances in the specific humoral and cellular defense as well as the presence of atypical lymphoid cells in skin and lymph node. The latter resembled the atypical T cells found in mycosis fungoides and Sézary syndrome. The possibility of the presence of either a cutaneous T cell lymphoma or unregulated T cell stimulation leading to concurrent immunodeficiency in this patient is discussed.

Patients described as having lamellar ichthyosis (LI) may not all have the same disorder. We studied nine patients, four of whom had erythroderma and generalized fine scaling, while the remainder had more marked scaling and hyperkeratosis without erythema. The former group is referred to as having nonbullous congenital ichthyosiform erythroderma (CIE), and the other is said to have LI. The clinical differences were paralleled by cell kinetic and histologic differences. The mean tritiated thymidine autoradiographic labeling indices were 9.36 +/- 4.05 and 19.70 +/- 5.84 for the LI and CIE groups, respectively. The histologic differences were delineated using 10-cm analogue scales and showed statistically significant differences for hyperkeratosis and parakeratosis. These data support the hypothesis that LI and CIE are separate disorders.

We describe two infants born with a collodion membrane; both were treated with a product containing 10% urea and 5% lactic acid and as a consequence were found to have a raised plasma urea concentration.

Ichthyosiform erythroderma is a rare phenomenon occurring in about 1/300,000 live births. Congenital unilateral ichthyosis, described in this case report, is a clinical variant of ichthyosis. Only five previous cases have been reported. In the patient described in this report, superimposed infection of the affected skin developed. Her immunologic system was intact. She manifested failure to thrive, in spite of an adequate caloric intake, and markedly delayed psychomotor development. This patient also demonstrated absorption from the affected dermis of topically applied urea hydrophilic base ointment. She died before her first birthday.

A family with a history of ichthyosis is described in which the type of scale was thin and fine, resembling that of ichthyosis vulgaris, but the inheritance is of the autosomal recessive type. We have reviewed our previous experience with 42 additional patients whose condition had been diagnosed as recessively inherited ichthyosis and conclude that there is considerable heterogeneity in the cutaneous manifestations. We suggest that it is not possible to classify all patients into categories such as lamellar ichthyosis or congenital ichthyosiform erythroderma, and it may be better to use a more general term such as recessive ichthyosis until specific causes can be established.

Psoriasis occurring in a patient with lamellar ichthyosis is reported. Similar self-limited episodes had occurred earlier. On histopathologic examination of a biopsy specimen, an eruptive plaque showed parakeratosis and a reduction in the granular layer. Electrophoretic analysis of the keratins isolated from the epidermis of a plaque showed a reduction in the amount of the 67 kd polypeptide compared to the keratins of ichthyosis epidermis. Both of these findings support the diagnosis of psoriasis. Epilyt, applied daily, was effective in removing scales.

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.

Sjögren-Larsson syndrome is a rare disorder of childhood characterized by ichthyosis, mental retardation, and spastic paraplegia. The authors report the case of a patient presenting a congenital neuroichtyosis and psychotic disorders, and discuss the nosology of their case.

A 39 years old female patient with congenital erythroderma is reported. The condition was considered as the non bullous type of Brocq's congenital ichthyosiform erythroderma until recently. The patient was admitted as she had generalized erythema, desquamation and oedema, pyrexia and oliguria. The scales were fine and small, quite different from those of lamellar ichthyosis. The patient developed a recidivant pustular eruption on palms, face and trunk. So the diagnosis was changed to congenital psoriasiform erythroderma and this was supported by histopathological examination of both scaling and pustular lesions. There was a remarkable improvement on amethopterin therapy. The case is discussed and the relevant litterature is reviewed.

We report the case of a 15-year-old girl with a uneventful family history. Her skin condition was clinically, histologically and ultrastructurally compatible with the diagnosis of ichthyosis congenita. She suffered from neurosensory deafness and oligophrenia. Further findings included dental aplasia, brachydactyly, clinodactyly and accessory cervical ribs. At the age of 14, a thyroid carcinoma was diagnosed. Therapy with a retinoid derivative (Ro 10-9359) resulted in a marked improvement of the ichthyosis. We assume a genetic syndrome with autosomal-recessive inheritance.

A one-day-old male premature baby was born to a G4P4 mother with the gestation age of 30 weeks. His birth weight was 2000 gm. He was noted to be covered with a thick, armor-like skin which is split by deep fissures and makes the feature of Ectropion and eclabium. His nose was flattened, only the nostrils were visible, and the external ears were underdeveloped. The hands and feet appeared to be swollen and crumpled. The genital organ was covered with thick fissured skin and it was impossible to distinguish sex by external appearance. Three days after delivery, the patient died of respiratory distress. He was found normal through general laboratory and chromosome study. However, dermatohistology showed hyperkeratosis, focal parakeratosis and hypogranulosis. Pathology showed PDA (patent ductus arteriosus), enlarged thymus and congestion of internal organs. Its etiology and pathogenesis somehow remain unknown. We hereby reported this harlequin fetus, the most severe type of lamellar ichthyosis, and discussed its incidence, pathogenesis, pathohistology, prognosis and the recent development in treatment.

Two sibs are described with Sjögren-Larsson syndrome. Another sib died in early life with signs which appear to be indicative of the same condition. In the two cases studied we have documented signs of peripheral nerve involvement (not previously reported in the literature) which point towards a pathological process acting on ectodermal structures to a greater extent than has previously been considered.

A harlequin fetus seen at birth was treated with etretinate and more general measures, including careful attention to fluid balance, calorie intake and temperature control. She improved, continued to develop, and had survived to 5 months at the time of this report.

The first born offspring of first-cousin parents was affected with a keratinization disorder thought to be nonbullous congenital ichthyosiform erythroderma (CIE). In each of three subsequent pregnancies, the parents elected to have prenatal diagnosis based on evaluation of fetal skin biopsies. The epidermis of fetus 1 was identical to normal 21-wk estimated gestation age (EGA) fetal epidermis, but because keratinization begins normally around 24 wk EGA, the procedure was repeated 4 wk later. A thin epidermis with a few layers of stratum corneum indicated a normal fetus and a healthy infant was born at term. Skin biopsy samples from fetus 2 gave conflicting results; the epidermis of one sample appeared normal but the second had 5-15 layers of incompletely keratinized cells superficial to basal and intermediate layers. The hair canals of both samples were hyperkeratotic. Pelleted amniotic fluid cells contained aggregates of incompletely keratinized epidermal cells and concentric rings of keratinized cells. The fetus was thought to be affected and the pregnancy terminated. Regional variation in epidermal thickness and keratinization was noted upon gross examination of the fetus and by histology of the skin. Marked hyperkeratinization of follicles was evident in all regions. No abnormal keratins were expressed in the affected epidermis but epidermal lipids analyzed from two body regions had a lower triglyceride content and a higher content of free sterols compared with age-matched, normal fetal epidermis. Immunolabeling for markers of differentiation revealed variable stages of epidermal differentiation according to region. Four structurally identical biopsy samples were obtained from a third fetus. The epidermis appeared normal for age and hair canals were keratinized to various extents. The pregnancy was continued and at 33 wk a male infant was born with a severe ichthyosis of the face and scalp and fine, white scaling on the body. The epidermis of both the severely and mildly affected regions of the newborn had a thick, compact stratum corneum and other features of CIE. Scars from all four fetal biopsies were identified on the trunk, in areas which appeared less affected clinically. This study reports, for the first time, the criteria for prenatal diagnosis of CIE and the variable expression of this disorder in the midtrimester fetus. More importantly, it demonstrates the risks and pitfalls of this in utero diagnosis based on epidermal morphology.

Epidermal keratinocytes separated from skin lesions of non-bullous congenital ichthyosiform erythroderma were investigated in an attempt at experimental reproduction of this keratinization disorder. In vitro studies on growth and differentiation of pathological keratinocytes isolated from the influence of the host's dermal and humoral components were performed using the immersed epidermal cell culture technique. Ten to 25-day-old confluent and stratified cultures were examined by means of photonic and electron microscopy, and stained with various differentiation markers for indirect immunofluorescence studies. The cultured epidermis showed low-grade differentiation and no clear-cut evenly distributed signs of the original disease. Grafting on congenitally athymic nude mice allowed further differentiation of the epidermal sheets and re-expression of the histologic and ultrastructural features of non-bullous congenital ichthyosiform erythroderma. Thus, the purely epidermal origin of this particular form of autosomal recessive ichthyosis could be confirmed. Large amounts of pathological keratinocytes generated from small skin biopsies may be used for experimental purposes after grafting on several athymic animals.

Rud's syndrome is a neuroichthyosis with hypogonadism, associated with mental deficiency and epilepsy. Short stature is a frequent component of the syndrome. The primary genetic defect and the pattern of inheritance have not yet been determined. A typical patient is presented, with mental deficiency, short stature, pypoacusia, muscular atrophy, tylosis, pseudoacanthosis nigricans and endocrine disturbances. The neuroichthyosis with hypogonadism must be considered Rud's syndrome. A classification of neuroichthyosis is proposed. In a first group is neuroichthyosis with hypogonadism, in the second group is neuroichthyosis with spasticity and in the third group, neuroichthyosis without hypogonadism or spasticity.

A unique form of congenital ichthyosis in two unrelated patients is described and characterized histologically by separation of the epidermis between the stratum corneum and the stratum granulosum. The clinical history, genetics, serially performed skin biopsies, and biochemical studies are reviewed. This form of ichthyosis is different from previously described entities. Lifelong peeling of the general body epidermis, pruritus, short stature, easily removed anagen hairs, and the ability to easily mechanically separate stratum corneum from the rest of the epidermis characterize the syndrome. In two families with this disorder, autosomal recessive inheritance is suggested. A low plasma tryptophan level as present in two patients with this disease. This inherited disorder of the epidermis was first described in 1924 before the genetics and histology of ichthyosis were extensively studied and is a distinct genetic and clinical entity to be considered in unusual cases of ichthyosis.