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Background Bazex–Dupré–Christol syndrome (BDCS; MIM301845) is a rare X-linked dominant genodermatosis characterized by follicular atrophoderma, congenital hypotrichosis and multiple basal cell carcinomas (BCCs). Previous studies have linked BDCS to an 11·4-Mb interval on chromosome Xq25-q27.1. However, the genetic mechanism of BDCS remains an open question. Objectives To investigate the genetic aetiology and molecular mechanisms underlying BDCS. Methods We ascertained multiple individuals from eight unrelated families affected with BDCS (F1–F8). Whole-exome (F1 and F2) and genome sequencing (F3) were performed to identify putative disease-causing variants within the linkage region. Array comparative genomic hybridization and quantitative polymerase chain reaction (PCR) were used to explore copy number variations, followed by long-range gap PCR and Sanger sequencing to amplify the duplication junctions and to define the head–tail junctions. Hi-C was performed on dermal fibroblasts from two affected individuals with BDCS and one control. Public datasets and tools were used to identify regulatory elements and transcription factor binding sites within the minimal duplicated region. Immunofluorescence was performed in hair follicles, BCCs and trichoepitheliomas from patients with BDCS and sporadic BCCs. The ACTRT1 variant c.547dup (p.Met183Asnfs*17), previously proposed to cause BDCS, was evaluated with t allele frequency calculator. Results In eight families with BDCS, we identified overlapping 18–135-kb duplications (six inherited and two de novo) at Xq26.1, flanked by ARHGAP36 and IGSF1. Hi-C showed that the duplications did not affect the topologically associated domain, but may alter the interactions between flanking genes and putative enhancers located in the minimal duplicated region. We detected ARHGAP36 expression near the control hair follicular stem cell compartment, and found increased ARHGAP36 levels in hair follicles in telogen, in BCCs and in trichoepitheliomas from patients with BDCS. ARHGAP36 was also detected in sporadic BCCs from individuals without BDCS. Our modelling showed the predicted maximum tolerated minor allele frequency of ACTRT1 variants in control populations to be orders of magnitude higher than expected for a high-penetrant ultra-rare disorder, suggesting loss of function of ACTRT1 variants to be an unlikely cause for BDCS. Conclusions Noncoding Xq26.1 duplications cause BDCS. The BDCS duplications most likely lead to dysregulation of ARHGAP36. ARHGAP36 is a potential therapeutic target for both inherited and sporadic BCCs. What is already known about this topic? Bazex–Dupré–Christol syndrome (BDCS) is a rare X-linked basal cell carcinoma susceptibility syndrome linked to an 11·4-Mb interval on chromosome Xq25-q27.1.Loss-of-function variants in ACTRT1 and its regulatory elements were suggested to cause BDCS. What does this study add? BDCS is caused by small tandem noncoding intergenic duplications at chromosome Xq26.1.The Xq26.1 BDCS duplications likely dysregulate ARHGAP36, the flanking centromeric gene.ACTRT1 loss-of-function variants are unlikely to cause BDCS. What is the translational message? This study provides the basis for accurate genetic testing for BDCS, which will aid precise diagnosis and appropriate surveillance and clinical management.ARHGAP36 may be a novel therapeutic target for all forms of sporadic basal cell carcinomas.

Background Mutations in the ST14 gene, encoding the serine protease matriptase, have been associated with ichthyosis-hypotrichosis syndrome (IHS), a Mendelian disorder with skin and hair manifestations which include, in addition to ichthyosis and hypotrichosis, hypohidrosis and follicular atrophoderma. However, the understanding of the specific consequences of mutations in ST14 on the development of this syndrome is incomplete. Results Using a targeted next-generation sequencing array of 38 ichthyosis-associated genes on a large cohort of 180 ichthyosis patients from a primarily consanguineous background, a previously unreported homozygous p.Asp482Asn mutation in ST14 was identified in a patient with IHS. This mutation affects an essential site within a ligand-binding domain of matriptase. Comparison with previous reports of IHS allowed further delineation of the phenotype of IHS in correlation with mutations present in these patients. Histological and ultrastructural analysis of skin and hair identified novel features in this disorder. Conclusions This study correlates genotypic and phenotypic features of the rare disorder, IHS, expands the spectrum of pathology associated with the disorder, and provides clinical evidence of the importance of the Asp482 amino acid, previously shown to have an essential role in matriptase activation.

Actin-Related Protein-Testis1 (ARP-T1)/ ACTRT1 gene mutations cause the Bazex-Dupré-Christol Syndrome (BDCS) characterized by follicular atrophoderma, hypotrichosis and basal cell cancer. Here, we report an ARP-T1 interactome (PXD016557) involved in ciliogenesis, endosomal recycling and septin ring formation. Consequently, ARP-T1 localizes to the midbody during cytokinesis and the basal body of primary cilia in G0. Tissue samples from BDCS patients show reduced ciliary length with significant correlations of ARP-T1 expression levels, confirmed by ACTRT1 knock down. We report that BDCS is a novel ciliopathy and the first case of a skin cancer ciliopathy, where ARP-T1 plays a critical role to prevent pathogenesis.

Background Bazex–Dupre–Christol syndrome (BDCS) is an X-linked dominantly inherited disorder affecting hair follicle structures. Currently, hypotrichosis, follicular atrophoderma and basal cell carcinomas are considered frequent symptoms of the disorder whereas milia are supposed to reflect infrequent clinical signs. Usually, basal cell carcinomas in this disease manifest from the second decade of life onwards. Case report Here, we studied a novel multigeneration family of German origin with BDCS. Interestingly, two family members developed pigmented basal cell carcinomas in early childhood, at the age of 3 and 5 years, respectively. The differentiation from other pigmented lesions was accomplished by both dermoscopy and histopathology. A thorough survey of the current literature revealed that milia were present in almost all patients with BDCS reported, as is the case in our family. Conclusions We suggest that milia should also be considered frequent symptoms in BDCS. For the first time, to the best of our knowledge, we describe the occurrence of pigmented basal cell carcinomas in BDCS during the first decade of life. Our observation emphasizes the importance of screening for cutaneous malignancies in this disorder already at young age.

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.

This paper suggests that there is probably a dominant, sex-linked type of chondrodysplasia punctata. Clinical data are reported for three girls with such a disorder. Two of their mothers showed a mild form of cicatricial alopecia. The pathognomonic dermatological findings in the children include erythematous skin changes and striated ichthyosiform hyperkeratosis during the first months of life. Later on, patterned ichthyosis, follicular atrophoderma, coarse, lusterless hair and cicatricial alopecia become evident. It is assumed that about one fourth of all cases with chondrodysplasia punctata reported in the literature belong to the dominant sex-linked type.

Autosomal recessive congenital ichthyosis (ARCI) is a clinically and genetically heterogeneous group of genodermatoses characterized by disorders of cornification. ARCI11 (MIM #602400) includes two syndromes caused by mutations in the ST14 (suppression of tumorigenicity 14) gene: IFAH (autosomal recessive congenital ichthyosis, follicular atrophoderma and hypotrichosis) and ARIH (autosomal recessive ichthyosis and hypotrichosis). All the reported ARCI11 cases so far belonged to consanguineous Turkish or Arab families]. We describe a novel p.Glu519Gln missense mutation in a patient affected by IFAH from a non consanguineous Rumanian family.

Bazex-Dupre-Christol syndrome is an X-linked dominantly inherited disorder characterized by congenital hypotrichosis, hypohidrosis, follicular atrophoderma, multiple milia and basal cell carcinomas. We present a girl and her family with this syndrome. Our patient, her 5 month old brother and her 17 year old brother had multiple milia and scalp and eyebrows hypotrichosis. Her 8 year old brother had multiple milia and follicular atrophoderma. Her mother had hypohidrosis and congenital scalp and eyebrows hypotrichosis, as well as a right paranasal lesion suggestive of basal cell carcinoma. We emphasize the importance of precise diagnosis and clinical follow up of these patients due to the possibility of developing basal cell carcinomas.

Bazex-Dupre-Christol syndrome (BDCS) [OMIM 301845] is an X-linked dominant disorder of the hair follicle characterized by multiple basal cell carcinomas, follicular atrophoderma, congenital hypotrichosis, and hypohidrosis. Additional features include multiple milia, trichoepitheliomas, and axillary hidradenitis suppurativa as well as a variety of other symptoms. Some patients with a diagnosis of BDCS have had poor school performance. But no other associated psychopathological disorders have been described in the literature. We describe the neuropsychological characteristics and the co-occurring psychopathological disorders in an Italian family (brother and sister, and their mother) affected by BDCS. The BDCS phenotype in this family was characterized by hypotrichosis, atrophoderma follicularis, milia, and trichoepitheliomas. No basal cell carcinomas were documented. At neuropsychological assessment the three affected family members all had a borderline cognitive level. Other identified psychopathological disorders included attention deficit hyperactivity disorder, executive deficits, academic difficulties, deficits in lexical skills, and internalizing problems. The presence of cognitive impairment in the three family members affected by BDCS suggests that cognitive impairment may be associated with the syndrome. It may be useful to assess neuropsychological performance in patients with BDCS to identify possible associated neuropsychological disorders.

Follicular atrophoderma is a rare anomaly observed mainly in the X-dominant form of chondrodysplasia punctata (Conradi-Hunermann-Happle syndrome) and in the X-linked dominant Bazex syndrome. We report on five Emirati sibs (three girls and two boys), 4–18 years old, with normal stature, diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse non-scarring hypotrichosis, and marked hypohidrosis. Steroid sulfatase activity, assessed in the two boys, was found to be normal. Electron microscopic studies of ichthyotic skin did not show any specific abnormality. The association of congenital diffuse ichthyosis with follicular atrophoderma and hypotrichosis has not been reported before. The patients were reminiscent of Bazex syndrome; however, ichthyosis is not a component of Bazex syndrome. We conclude that this syndrome of congenital ichthyosis with follicular atrophoderma represents a new autosomal recessive genodermatosis. Am. J. Med. Genet. 75:186–189, 1998. © 1998 Wiley-Liss, Inc.

Bazex-Dupre-Christol syndrome (BDCS) is an X linked dominant disorder of the hair follicle characterised by follicular atrophoderma, multiple basal cell carcinomas, hypotrichosis, milia, and localised hypohidrosis. Follicular atrophoderma (FA) are follicular funnel shaped depressions, "ice pick marks", seen most commonly on the dorsum of the hands. We describe the first known Scottish family with this syndrome, five affected members spanning three generations. They have hypohidrosis confined to the face, coarse hair, dry skin, milia, and follicular atrophoderma. All the adults have a history of multiple basal cell carcinomas. None of them has any skeletal feature suggestive of Gorlin's syndrome. The clinical features, skin histology, and scanning electron microscopic (SEM) examination of the hair are described and illustrated. The features are compared with 15 previous reports of BDCS and four reports in which this is a possible diagnosis are also reviewed. BDCS should be considered as a differential diagnosis in patients with early onset or familial basal cell carcinomas.

Bazex-Dupré-Christol syndrome is an inherited condition with skin cancer predisposition characterized by follicular atrophoderma, hypotrichosis, and early onset of multiple basal cell carcinomas. Previous reports suggested an X-linked mode of inheritance. We therefore performed linkage analysis with microsatellite markers of the X chromosome in three families. We obtained evidence for X-linkage and regional assignment to Xq24-q27 of this syndrome (maximal lod score = 5.26 with a recombination fraction of 0% at the DXSl192 locus). This represents a first step towards the identification of a gene involved in hair follicle development and skin tumor formation.

A seven-year-old girl was born with red, scaly skin that later evolved into hypopigmentation and follicular atrophoderma in a widespread distribution that followed Blaschko lines. She also had patchy, scarring alopecia, left microphthalmia, bilateral cataracts, dysmorphic facies, short stature, hip dysplasia, and vertebral abnormalities. An elevated plasma 8(9)-cholestenol level confirmed the diagnosis of Conradi-Hunermann-Happle syndrome, which is caused by mutations in the emopamil binding protein (EBP) gene. This reports highlights the evolution of clinical findings over time in this X-linked dominant form of chondrodysplasia punctata.

Background. We present the case of a 32-year-old woman with a large recurrent multifocal basal cell carcinoma on the scalp. Conspicuous accompanying symptoms were multiple periorbital milia, hypotrichosis of the body and the scalp, and hypohidrosis. The sparse hair of the scalp showed further abnormalities such as pili torti, as well as flattened, irregularly curly hairs. Objective. In 1964, Bazex et al. described a syndrome characterized by congenital hypotrichosis, follicular atrophoderma, and basocellular neoplasms that included basal cell nevi and early onset basal cell carcinomas. The Bazex–Dupre–Christol syndrome is a rare X-linked dominant disease. A sporadic occurrence with the typical constellation of these symptoms has not yet been reported. The lack of a positive family history and no signs of follicular atrophoderma argues for a sporadic occurrence of a Bazex–Dupre–Christol-like syndrome. The case reported shares several features with the classic Bazex–Dupre–Christol syndrome. Conclusion. Our report documents the necessity to look for early development of basal cell carcinomas in patients who show signs of the epidermal malformations described.

Bazex-Dupre-Christol syndrome is a rare genodermatosis with cancer predisposition, characterized by follicular atrophoderma, multiple milia, congenital hypotrichosis, hypohidrosis and basal cell malformations that include nevoid basal cell carcinomas of early onset. We present two patients with this syndrome, a 1-year-old boy with diffuse scalp and eyebrows alopecia, milia papules on the face, ears, trunk, and limbs. Hypohidrosis was observed on his trunk and head. His 16-year-old mother had identical changes since childhood, with hair fragility, and multiple atrophic "ice pick" follicular depressions on the dorsa of her hands. She also had a basal cell carcinoma on her face. Microscopic examination of hairs from the mother revealed abnormalities such as diameter irregularities, broken shafts, trichorrexis nodosa and pili bifurcatti. Pili bifurcatti is an uncommon hair shaft dysplasia that has not before been observed in Bazex-Dupre-Christol syndrome.

Conradi-Hunermann-Happle syndrome, or X-linked dominant chondrodysplasia punctata, is a rare genetic disorder characterized by skeletal dysplasia, stippled epiphyses, cataracts, transient ichthyosis and atrophic residua in a mosaic pattern. Mutations in the gene encoding the emopamil-binding protein have been identified as an underlying cause. A 5-year-old girl presented for evaluation of ill-defined patches of cicatricial alopecia. In addition, subtle follicular atrophoderma, esotropia, craniofacial asymmetry and short stature were noted. Her history revealed widespread scaly erythema and eye surgery for congenital cataract in the first months of life. Diagnosis of Conradi-Hunermann-Happle syndrome was confirmed by plasma sterol analysis showing markedly elevated levels of 8(9)-cholestenol and 8-dehydrocholesterol and by detection of a missense mutation (c.307G>A; p.E103K) in the emopamil-binding protein gene. We suggest that plasma sterol analysis is a reliable method of establishing the diagnosis of Conradi-Hunermann-Happle syndrome, even in patients with less striking phenotypical changes beyond infancy.

We describe the case of a 13-year-old girl suffering from chondrodysplasia punctata, associated with ichthyosis arranged along Blaschko's lines, follicular atrophoderma, cicatricial alopecia and coarse, lusterless hair. The patient also showed a congenital cataract of the right eye, dysplastic facial appearance and symmetrical shortening of the tubular bones. The pathogenetic concept of functional X-chromosome mosaicism is reviewed as well as the recent results obtained by molecular research that have failed, so far, to solve the problem of regional assignment of the underlying X-linked gene.

A 6-year-old male child presented with progressive hypertrophy and discoloration of all 20 nails. Further evaluation revealed milia in bilateral concha and face, which were present since infancy. Other findings included atrophoderma over bilateral sides of lateral canthi of eyes and absent lower central incisors. Past medical and family history had remarkable findings such as natal teeth and similar nail changes in his elder sister. Similar nail changes, milia and focal plantar keratoderma were present in his father and elder sister. The patient's clinical presentation and history were compatible with pachyonychia congenita subtype 2.

Background: The Bazex-Dupre-Christol syndrome is characterized by follicular atrophoderma, congenital hypotrichosis, and basal cell neoformations that include basal cell carcinomas and basal cell nevi. Observations: We describe a large family in which 20 persons across four generations present with typical features of the Bazex-Dupre-Christol syndrome. However, the clinical picture in this family differs with regard to gender and age. Male subjects have a uniformly severe disease, whereas female subjects exhibit a range of severity of the syndrome. The most striking difference between male and female subjects is provided by hypotrichosis. In male subjects, hypotrichosis is diffuse and affects all scalp hairs. On the other hand, female subjects do not have hypotrichosis, but normal hairs are intermingled with abnormal hairs. In infancy and childhood, multiple milia are present, whereas in adults only a few milia are observed. Conclusions: The family pedigree seems to be consistent with an X-linked inheritance, since male-to-male transmission does not occur. Moreover, further evidence of an X-linked dominant mode of inheritance could be derived from the observation of gender differences that can be attributed to the lyonization phenomenon in female subjects. From a clinical and morphologic point of view, the Bazex-Dupre-Christol syndrome seems to be a disorder of the hair follicle. ( Arch Dermatol. 1994;130:337-342 )

Follicular atrophoderma has been associated with a variety of findings. In our patient's family the disease was present in the mother and all of her living children. Scrotal tongue was also found in all but one child. We think that follicular atrophoderma is probably inherited as an autosomal dominant trait.

四肢伸側に毛孔性皮膚萎縮を持つ中年男子に基底細胞癌が多発した。他の5人兄弟には皮疹をみなかつたが, 母親にも同様の毛孔性皮膚萎縮をみたことよりBazex症候群が疑われた。毛孔性皮膚萎縮は幼児期より前腕, 下腿の伸側ではつきりしており, ほとんどに体毛を伴つたが一部では脱落していた。基底細胞癌は42才時より顔面に初発し, 以後, 頭頸部や限界線照射の既往がある躯幹にも多発した。以上の臨床所見と, 頭髪, 発汗の異常はみられなかつたことを考えあわせ不完全型のBazex症候群と考えた。なお患者は22才時, 尋常性乾癬のため躯幹に限界線照射を受けたが, 両部にも多数の基底細胞癌が出現したことより, Bazex症候群患者には放射線治療は禁忌と考えた。

Chodrodysplasia punctata is a very rare disease, and was first described by Conradi in 1914. Almost 200 cases have been reported in the world, and 33 cases in Japan.The essential feature of this condition is the presence of stippled foci of calcification within the hyaline cartilage in infancy. And this disease is frequently associated with multiple congenital abnormalities, as cataract, saddle nose, follicular atrophoderma, contractures of joints, dwarfing of the limbs, kyphoscoliosis, mental retardation, etc.Three cases of Conradi-Hunermann type of chondrodysplasia punctata, diagnosed in infancy, are presented. They were followed for about 10 years.

A case of Conradi's disease (chondrodystrophia calcificans congenita, congenital stippled epiphyses) is reported in which the evolution of the disease was followed for 15 years. At birth the patient showed stippling of the epiphyses, abnormalities of the vertebral bodies, shortening of the right femur, bilateral congenital cataracts, saddle-nose deformity, and blotchy erythema of the skin and scalp. By the age of 6 months most of the epiphyseal stippling had disappeared and the vertebral column abnormalities had begun to produce kyphosis. By 15 years of age she had severe kyphoscoliosis, marked shortening of the right leg, short stature, cicatricial alopecia, coarse and lusterless hair, follicular atrophoderma, saddle-nose deformity, cataracts, irregular dentition, and low normal intelligence. Despite the early disappearance of epiphyseal stippling, recognition of the associated abnormalities may allow diagnosis of Conradi's disease in later life.

In 1943 Miescher (1) reported peculiar atrophic changes of the skin of body and scalp in a 7 year old Swiss girl. There were spots of atrophic alopecia on the scalp, and on the extremities and trunk irregular zones in which dimple-like depressions were found at the place of follicular orifices. The child was very small and had thoracic kyphoscoliosis, lumbar lordosis, luxation of the right hip, a considerably shortened right leg, and a moderately shortened left arm. Five years earlier, Burckhardt (2) has described the skeletal condition of the same child, then 2 years old, as chondrodystrophia foetalis calcarea. In the English speaking countries this disease is called chondrodystrophia calcificans congenita, chondro-osseous dystrophy with punctate epiphyseal dysplasia, or similar variations.

A dominant inheritance leading to development of nevoid basal cell epitheliomas on the face and follicular atrophoderma on the extremities constitute the two constant manifestations of Bazex syndrome. A patient with both manifestations on the trunk who fulfilled all the criteria for a diagnosis of nevoid basal cell epitheliomas is described. Histopathology of the basal ceil cancer corresponded to that of the fibroepithelial tumor, thus differing from the more common nodular and trichoepitheliomatous persentations. Difficulty in associating the atrophoderrna with a hair follicle (histologically) arises because the latter ceases to exist as a functional unit.

The X-linked dominant Conradi—Hunermann syndrome (CHS-XD, McKusick 30295) is characterized by ichthyosiform erythroderma at birth giving way to whorled areas of hyperkeratosis, streaky follicular atrophoderma, cicatricial alopecia and coarse lustreless hair. The facies typically shows frontal bossing, a flattened nasal bridge and malar hypoplasia. Cataracts are common. Skeletal abnormalities include the transient punctate epiphyseal calcifications, asymmetric limb shortening and short stature. According to Happle (1981), CHS-XD can be readily distinguished from an autosomal dominant form of the Conradi—Hunermann syndrome (CHS-AD, McKusick 11865) because the latter does not produce whorled/streaky skin lesions or cataracts. Differentiation between CHS-XD and autosomal recessive rhizomelic chondrodysplasia punctata (RCP, McKusick 21510) presents no serious problem: patients with RCP have severe, symmetrical proximal limb shortening, marked psychomotor retardation, mild ichthyotic skin changes and they rarely survive beyond 2 years of age.

Five patients from a single family are reported who have an inherited condition of which the main features are follicular atrophoderma, abnormalities of scalp hair and multiple basal cell carcinomas. Thes abnormalities are consistent with the syndrome described by Bazex et al. (1964). The pattern of inheritance of this condition is discussed.

X-Linked dominant ichthyosis is a rare disorder of keratinization and represents a cutaneous hallmark of a distinct type of chondrodysplasia punctata [4]. Clinically, this type of keratinization disorder gives rise to ichthyosiform erythroderma in the newborn, and mild scaling with follicular atrophoderma in older children. We have recently demonstrated that, in Xlinked dominant ichthyosis, the slightly thinner epidermis displays characteristic ultrastructural features, including vacuolization of the granular cell layer and regular keratohyalin formation [6]. As an incidental finding, alterations of the epidermal Langerhans cells were noted. This prompted us to reexamine the behaviour of Langerhans cells in this rare ichthyosis using ultrastructural and quantitative methods. The study was performed on biopsies obtained from a 4-week-old baby and a 14-year-old girl who both showed the typical signs and symptoms of Xlinked dominant chondrodysplasia punctata [5]. The biopsies were taken from ichthyotic areas of the upper trunk and were processed by routine methods for electron microscopy. The numerical density of the epidermal Langerhans cells was evaluated directly by electron-microscopic examination of ultrathin sections. For this purpose, ultrathin sections of tissue blocks stained with lead citrate and uranyl acetate were mounted on Formvar-coated 50-mesh grids, and all of the epidermal Langerhans cells within one grid square were counted. Subsequently, the evaluated square was recorded on a 35-mm film in order to determine the epidermal surface within this square

A family with Conradi-Hunermann syndrome was identified after a scaly, erythrodermic neonate was seen. Although examination of the female infant yielded no specific findings suggestive of the syndrome, her mother and maternal great-grandmother had features that allowed the diagnosis to be made. Only after 5 months did the streaky hyperkeratotic pattern characteristic of the syndrome develop in the child. Family members bore other stigmata, including patchy cicatricial alopecia, coarse hair, follicular atrophoderma, frontal bossing, cataracts, short stature, and short proximal limbs. The pattern of inheritance in this family is compatible with that of an X-linked dominant genodermatosis with variable expression. Histopathologic findings from skin biopsy specimens were psoriasiform rather than ichthyotic. Decreased peroxisomal enzyme activity was discovered on fibroblast cultures, linking this syndrome with other peroxisomal disorders. Treatment with oral bezafibrate and clofibrate, which are potential inducers of hepatic peroxisomes, did not result in clinical improvement. It is recommended that usage of the term chondrodysplasia punctata be restricted to the descriptive radiologic finding of stippled calcifications and that Conradi-Hunermann syndrome refer only to the disease described herein, which is transmitted as an X-linked dominant trait.

To the Editor.— In the October 1978 issue of theArchives(114:1479-1483, 1978), Dr Curth reconsidered her interesting case report of 1949 1 dealing with the association of follicular atrophoderma and chondrodysplasia punctata. With regard to cause, Dr Curth now suggests either an X-linked dominant gene that is lethal in hemizygous males or an autosomal dominant gene with sex-limited expression. The following arguments are advanced to show that the first possibility is more likely. The concept of X-linked dominant chondrodysplasia punctata was proposed because of two facts. 2,3 First, some patients with chondrodysplasia punctata show widespread atrophic skin lesions and alopecia, and occasionally also pigmentary disturbances that may easily be confused with incontinentia pigmenti of the Bloch-Sulzberger type. This pattern of skin lesions suggests functional X-chromosome mosaicism. Consequently, in involved areas the X chromosome carrying the mutant gene should be active, whereas in uninvolved skin the normal X chromosome should be

• Follicular atrophoderma apparently does not occur alone but is associated with other abnormalities. It is present in three groups: (1) If it is associated with chondrodystrophia calcificans congenita, it occurs only in girls and is due either to an X-chromosomal gene causing the changes in the heterozygote (ie, in the female sex) and prenatal death in the hemizygous state (ie, in the male sex), or to an autosomal dominant gene with expression almost wholly limited to the female sex; (2) If it is associated with Bazex's syndrome, it occurs in male and female persons in successive generations and is due either to an autosomal dominant gene or to an X-linked dominant gene; and (3) If it occurs in association with keratosis palmoplantaris dissipata, keratosis follicularis, and hyperhidrosis palmoplantaris, it may be due to a recessive gene or a mutation. (Arch Dermatol114:1479-1483, 1978)

• Seven members of one family had a rare, inherited syndrome of follicular atrophoderma, basal cell carcinomas, and localized anhidrosis. Associated findings in some subjects were generalized hypohidrosis and "eczema" involving the face shortly after birth. This syndrome shows dominant inheritance, possibly x-linked. Follicular atrophoderma is an important skin manifestation, as it has been associated in all reported cases with other systemic or cutaneous abnormalities. ( Arch Dermatol 113:948-951, 1977)

To the Editor. —In their excellent paper entitled ``Bullous Variety of Incontinentia Pigmenti (Bloch-Sulzberger)'' (A. M. A.Arch. Dermat. & Syph. 65 :557-567 [May] 1952), Epstein, Vedder, and Pinkus state that they saw no signs of follicular atrophoderma upon examination of their patient at the age of 16 months. The authors, however, noted agenesis of the skin appendages in the histologic pictures of specimens taken at the ages of 19 days and one year. Agenesis of skin appendages was noted in the histologic pictures of follicular atrophoderma of two girls observed by me (Curth, H. O.: Follicular Atrophoderma and Pseudopelade Associated with Chondrodystrophia Calcificans Congenita, J. Invest. Dermat. 13 :233-247 [Nov.] 1949) at the ages of 8 and 9 years, respectively. In the 9-year-old child and her 4-year-old sister incontinentia pigmenti was also present. I saw my patients with incontinentia pigmenti and their 37-year-old mother for the first time at