Absent Eyebrows Research Articles

One Mutation of the ED1 Gene in a Chinese Han Family with X-Linked Hypohidrotic Ectodermal Dysplasia

Dear Editor: Hypohidrotic ectodermal dysplasia (HED) is characterized by the abnormal development of the eccrine sweat glands, hair, and teeth. The X-linked form of the disease, caused by mutations in the ED1 gene, represents the majority of HED cases. Most subjects with X-linked HED harbor mutations in the ED1 gene, which has a detection rate of 63% to 95%1. X-linked HED mainly occurs in men, whereas females are carriers. The affected organs are of ectodermal origin, but the nervous system is usually unaffected. Atopic dermatitis and bronchial asthma are frequent complications2. Here we in a Chinese family with X-linked HED show one mutation. The family belonged to the Han population of China and comprised two patients and their parents (Fig. 1). Two affected males fulfilled the diagnostic criteria of this disorder. The proband was a 5-year-old boy. He had fine curly sparse hair, abnormal teeth, and dryness of several skin areas, and had a recurrent fever of 38℃ due to the absence of sweating since birth, which was more frequent and obvious in summer and during moving. He also had a characteristic facial appearance of X-linked HED, including frontal bossing, absent or scarce eyebrows, a saddle nose, periorbital wrinkling and hyperpigmentation, and thickened, everted lips (Fig. 1)3. In addition, his mother's brother had similar symptoms and clinical onset. Both their parents were healthy. Fig. 1 The proband and his uncle had similar symptoms and clinical onset. Both their parents were healthy. Clinical features of the proband. (A) Sparse hair, (B) hypodontia, (C) extra ear malformation, (D) abnormal nail. After obtaining informed consent, blood samples were collected from members of the family and 100 unrelated population-matched controls. Genomic DNA was extracted from the peripheral blood lymphocytes by standard procedures using Flexi Gene DNA kits (Qiagen, Shanghai, China), and was stored at -80℃ before the test. Eight coding exons and flanking sequences of the ED1 gene were amplified by polymerase chain reaction (PCR) using primers reported previously4. After the amplification, the PCR products were analyzed by agarose gel electrophoresis, and purified with a QIAquick PCR purification kit (Qiagen). Finally, they were sequenced using an ABI-PRISM 3730XL automated DNA sequencer with forward/reverse universal and internal primers. The ED1 gene encodes a protein, ectodysplasin-A, recognized to be a member of the tumor necrosis factor (TNF) superfamily of ligands, which may be associated with its function. Ectodysplasin-A is involved in the regulation of ectodermal morphogenesis. To date, above 206 mutations in the ED1 gene have been included in the homo-sapiens gene bank, including missense mutations, nonsense mutations, splice junction mutations, small deletion/insertion mutations and large deletion or molecular transposition. Direct DNA sequence analysis showed one missense mutation (c.1133C>T) in exon 8 of the ED1 gene in the proband and his mother's brother. This mutation, located in the TNF homology domain, resulted in a change of Threonine (ACG) residue at codon 378 to Methionine (ATG) (p.T378M). At the same nucleotide position, the proband's mother was heterozygote with wild and mutant types. And this mutation was not found in the proband's father or 100 normal controls (Fig. 2). This result suggested that the c.1133C>T (p.T378M) mutation of the ED1 gene may be the pathologic cause of this X-linked HED Chinese family with. Fig. 2 Mutational analysis of the ED1 gene. (A) ATG; the patient showed a point mutation at nucleotide 1133 (C>T). (B) ANG; heterozygous double peaks of nucleotide C and T at the same position in his mother. (C) ACG; father and normal controls. In summary, we demonstrated one missense mutation p.T378M in the ED1 gene responsible for X-linked HED in the Chinese Han population. We hope this result will be useful for genetic counseling, carrier detection and prenatal diagnosis in X-linked HED families.

A transient myelodysplastic/myeloproliferative neoplasm in a patient with cardio‐facio‐cutaneous syndrome and a germline BRAF mutation

A male infant, born at 32 weeks gestation by cesarean because of hydrops fetalis, presented with multiple anomalies, such as sparse and curly scalp hair, absent eyebrows, frontal bossing, an atrial septal defect, pulmonary artery stenosis, and whole myocardial thickening. He was clinically diagnosed with cardio-facio-cutaneous (CFC) syndrome, and was confirmed to have a germline V-raf murine sarcoma viral oncogene homologue B1 (BRAF) c.721 A>C mutation. At 1 month of age, he presented with a transient myelodysplastic/myeloproliferative neoplasm (MDS/MPN), which improved within a month without the administration of antineoplastic agents. This is the first report of CFC syndrome with MDS/MPN. The coexistence of MDS/MPN may be related to this BRAF c.721 A>C mutation.

Ulerythema Ophryogenes, A Rarely Reported Cutaneous Manifestation of Noonan Syndrome: Case Report and Review of the Literature

Ulerythema ophryogenes (also known as keratosis pilaris atrophicans faciei) is a rarely reported cutaneous manifestation of Noonan syndrome. Recognizing ulerythema ophryogenes as a cutaneous association in Noonan syndrome may aid in the diagnosis of this relatively common genetic condition. We present a case of a patient with Noonan syndrome and ulerythema ophryogenes associated with a SOS1 mutation and review the literature on this association. To the best of our knowledge, this is the second case of Noonan syndrome proven to be due to an SOS1 mutation in which ulerythema ophryogenes was clinically recognized and specifically diagnosed. The presence of ulerythema ophryogenes in a patient with Noonan syndrome increases the likelihood of a SOS1 mutation. Further reports by dermatologists and medical geneticists documenting ulerythema ophryogenes and not just descriptions of sparse or absent eyebrows will help support this genotype-phenotype correlation.

Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development

The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction. To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations. This was a cross-sectional study. Dermatological surveys were designed by the authors and were completed by parents of mutation-positive individuals with CS at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatological examinations were performed by the authors at the CSFN conferences. Cutaneous papillomas were reported in 33 of the 46 (72%) participants, with age of onset ranging from infancy to 22years. Individuals with CS are more likely than patients with cardiofaciocutaneous syndrome (CFC) to present with cutaneous papillomas (72% vs. 5%, P<0·001) and palmoplantar keratoderma (76% vs. 36%, P<0·001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (9% vs. 90%, P<0·001) or keratosis pilaris (33% vs. 80%, P=0·001). This study also identified that loose, redundant skin on the hands and feet, 'stippled' dermatoglyphs (pachydermatoglyphia) on the fingertips (eight of 26, 31%) and acanthosis nigricans (17 of 46, 37%) are frequent features of CS. While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatological features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes.

Congenital hypotrichosis, eruptive milia, and palmoplantar pits: A case report with review of literature

We report a ten-month-old male infant, presenting with congenital hypotrichosis of scalp, absence of eyebrows and eyelashes. He also had multiple milia over face and extremities along with palmoplantar pits. The infant was born to third degree consanguineous marriage. None of the family members had similar disease. Histopathology was consistent with milia. Based on these findings, a diagnosis of unclassified ectodermal dysplasia was made.

Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis/woolly hair in 17 consanguineous families from Pakistan

Autosomal recessive hypotrichosis/woolly hair is a rare genetic hair loss disorder characterized by sparse scalp hair/woolly hair, sparse to absent eyebrows and eyelashes, sparse axillary and body hair in affected individuals. This form of hair loss results from mutations in either LPAR6 or LIPH gene. To identify mutations in LPAR6 and LIPH genes in 17 consanguineous Pakistani families showing features of hypotrichosis/woolly hair. Genotyping in 17 families was carried out using polymorphic microsatellite markers linked to genes causing autosomal recessive hypotrichosis/woolly hair phenotype. To screen for mutations in LPAR6 and LIPH genes, all of their exons and splice junction sites were amplified by PCR and sequenced using an automated DNA sequencer. Genotyping with polymorphic microsatellite markers showed linkage in eight families to LPAR6 and in nine families to LIPH gene. Sequence analysis revealed four recurrent mutations (p.Phe24HisfsX28; p.Asp63Val; p.Gly146Arg; p.Ile188Phe) in LPAR6 and two recurrent mutations (p.Trp108Arg; p.Ile220ArgfsX29) in LIPH gene. Comparison of the haplotypes generated by typing LPAR6 and LIPH genes linked microsatellite markers in different families suggested common founder natures of the two mutations (c.66_69insCATG and c.659_660delTA). Mutations identified in the present study extend the body of evidence implicating LPAR6 and LIPH genes in pathogenesis of human hereditary hair loss.

Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (poikiloderma) associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to cancer. The prevalence is unknown but around 300 cases have been reported in the literature so far. The diagnostic hallmark is facial erythema, which spreads to the extremities but spares the trunk, and which manifests itself within the first year and then develops into poikiloderma. Two clinical subforms of RTS have been defined: RTSI characterised by poikiloderma, ectodermal dysplasia and juvenile cataracts, and RTSII characterised by poikiloderma, congenital bone defects and an increased risk of osteosarcoma in childhood and skin cancer later in life. The skeletal abnormalities may be overt (frontal bossing, saddle nose and congenital radial ray defects), and/or subtle (visible only by radiographic analysis). Gastrointestinal, respiratory and haematological signs have been reported in a few patients. RTS is transmitted in an autosomal recessive manner and is genetically heterogeneous: RTSII is caused by homozygous or compound heterozygous mutations in the RECQL4 helicase gene (detected in 60-65% of RTS patients), whereas the aetiology in RTSI remains unknown. Diagnosis is based on clinical findings (primarily on the age of onset, spreading and appearance of the poikiloderma) and molecular analysis for RECQL4 mutations. Missense mutations are rare, while frameshift, nonsense mutations and splice-site mutations prevail. A fully informative test requires transcript analysis not to overlook intronic deletions causing missplicing. The diagnosis of RTS should be considered in all patients with osteosarcoma, particularly if associated with skin changes. The differential diagnosis should include other causes of childhood poikiloderma (including dyskeratosis congenita, Kindler syndrome and Poikiloderma with Neutropaenia), other rare genodermatoses with prominent telangiectasias (including Bloom syndrome, Werner syndrome and Ataxia-telangiectasia) and the allelic disorders, RAPADILINO syndrome and Baller-Gerold syndrome, which also share some clinical features. A few mutations recur in all three RECQL4 diseases. Genetic counselling should be provided for RTS patients and their families, together with a recommendation for cancer surveillance for all patients with RTSII. Patients should be managed by a multidisciplinary team and offered long term follow-up. Treatment includes the use of pulsed dye laser photocoagulation to improve the telangiectatic component of the rash, surgical removal of the cataracts and standard treatment for individuals who develop cancer. Although some clinical signs suggest precocious aging, life expectancy is not impaired in RTS patients if they do not develop cancer. Outcomes in patients with osteosarcoma are similar in RTS and non-RTS patients, with a five-year survival rate of 60-70%. The sensitivity of RTS cells to genotoxic agents exploiting cells with a known RECQL4 status is being elucidated and is aimed at optimizing the chemotherapeutic regimen for osteosarcoma.

A Homozygous Nonsense Mutation in the Human Desmocollin-3 ( DSC3) Gene Underlies Hereditary Hypotrichosis and Recurrent Skin Vesicles

Desmosomes are the major players in epidermis and cardiac muscles and contribute to intercellular binding and maintenance of tissue integrity. Two important constituents of desmosomes are transmembrane cadherins named desmogleins and desmocollins. The critical role of these desmosomal proteins in epithelial integrity has been illustrated by their disruption in mouse models and human diseases. In the present study, we have investigated a large family from Afghanistan in which four individuals are affected with hereditary hypotrichosis and the appearance of recurrent skin vesicle formation. All four affected individuals showed sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid were observed on the affected individuals' scalps and on most of the skin covering their bodies. A scalp-skin biopsy of an affected individual showed mild hair-follicle plugging. Candidate-gene-based homozygosity linkage mapping assigned the disease locus to 8.30 cM (8.51 Mbp) on chromosome 18q12.1. A maximum multipoint LOD score of 3.30 (theta = 0.00) was obtained at marker D18S877. Sequence analysis of four desmoglein and three desmocollin genes, contained within the linkage interval, revealed a homozygous nonsense mutation (c.2129T>G [p.Leu710X]) in exon-14 of the desmocollin-3 (DSC3) gene.

Mutations in theP2RY5gene underlie autosomal recessive hypotrichosis in 13 Pakistani families

Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. Affected male individuals have normal beard hair. To search for pathogenic mutations in the human P2RY5 gene in Pakistani families with autosomal recessive hereditary hypotrichosis. In the present report, 16 unrelated consanguineous Pakistani families having multiple affected individuals with autosomal recessive hypotrichosis were investigated. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Thirteen of the families showed linkage to the LAH3 locus on chromosome 13q14.11-q21.32. These families were then subjected to direct sequencing of the P2RY5 gene, which encodes a G protein-coupled receptor. Sequence analysis of the P2RY5 gene revealed two novel missense mutations (c.742A>T; p.N248Y and c.830C>T; p.L277P) in three families. Five previously described mutations including three missense (c.188A>T; p.D63V, c.436G>A; p.G146R, c.562A>T; p.I188F), one insertion (c.69insCATG; p.24insHfsX52) and one complex deletion (c.172-175delAACT; 177delG; p.N58-L59delinsCfsX88) were detected in the other 10 families. Mutations revealed in the present study extend the body of evidence implicating the P2RY5 gene in the pathogenesis of human hereditary hair loss.

Novel missense mutations in lipase H (LIPH) gene causing autosomal recessive hypotrichosis (LAH2)

Autosomal recessive hypotrishosis (LAH2) is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. However, affected male individuals have normal beard hair. Mutations in lipase H (LIPH) gene, located on chromosome 3q26.33, have been shown to be responsible for LAH2 type of hypotrichosis. To search for pathogenic mutations in LIPH gene at LAH2 locus in Pakistani families demonstrating autosomal recessive hypotrichosis. In the present study we have ascertained two large unrelated consanguineous Pakistani families (A and B) inherited autosomal recessive form of hypotrichosis. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene at LAH2 locus on chromosome 3q26.33. These families were then subjected to direct sequencing of the LIPH gene. Sequence analysis of the LIPH gene revealed two novel missense mutations (c.2T>C; p.M1T and c.322T>C; p.W108R) in the two families. The mutations reported here are the first missense mutations identified in the LIPH gene, which extend the body of evidences implicating the LIPH gene in the pathogenesis of human hereditary hair loss.

P38.09: Prenatal sonographic findings in a case of cardio‐facio‐cutaneous syndrome

The differential diagnosis of the karyotypically normal fetus with cystic hygromas is extensive, and includes several syndromes for which DNA diagnosis can now be done. We present a case in which cystic hygromas had been seen at 17 weeks. Karyotyping was normal. On our initial sonogram, at 21 weeks, findings included cystic hygroma, anteriorly displaced aorta, prominent superior vena cava, and globular appearance to the left ventricle. Polyhydramnios and a protruberant fetal tongue developed in the third trimester. Delivery was prompted by cessation of fetal movement at 32 weeks gestation. Cord blood gas studies were normal. The infant had dysmorphic features and hypotonia and developed progressive cardiomyopathy with pulmonic stenosis and concentric biventricular hypertrophy. Differential diagnosis included Noonan, Costello, and CFC syndromes. The neonate subsequently expired. When DNA testing for CFC became available, a stored specimen was checked, and demonstrated a heterozygous missense mutation (c.1931 G > T) in exon 11) of the BRAF gene consistent with the diagnosis of CFC syndrome. Cardio-facio-cutaneous (CFC) syndrome is a rare, devastating, sporadic syndrome which has recently been linked to gain-of-function mutations in the BRAF, KRAS, MEK1 and MEK2 genes of the RAS-extracellular signal-regulated kinase pathway. Abnormalities include developmental delay, postnatal growth impairment, characteristic facial features (prominent forehead, temporal narrowing, hypotelorism, posteriorly rotated ears) with or without web neck, cutaneous manifestations (sparse brittle hair, absent eyebrows, and hyperkeratosis of the palms and soles), and a variety of cardiac anomalies, including pulmonic stenosis and hypertrophic cardiomyopathy, often manifest only after birth. In utero diagnosis has not been described. Whether the unique cardiac findings described here will be seen in other cases awaits further sonographic observations. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

General anesthesia for a patient with deletion 6q syndrome in addition to laryngomalacia undergoing dental treatment

Chromosome 6 deletions are very rare (1,2), and deletion 6q syndrome is clinically characterized by mental and/or neuromotor retardation and microcephaly (3). Other alterations frequently observed are decreased biparietal diameter, hypertelorism, hypotelorism, absent eyebrows, prominent eyes with ptosis, receding chin, dysmorphic ears, large extremities, prominent nasal bridge, long philtrum, epicthus, strabismus, and micrognathia (3-5). Laryngomalacia is the most common congenital laryngeal anomaly and the most frequent cause of stridor in infants (6-11). We report the case of a 14-year-old male patient with both deletion 6q syndrome and laryngomalacia, who we treated for multiple dental caries. He had a medical history of tracheotomy at age 11 years for laryngomalacia, and has suffered from epileptic attacks and aspiration pneumonia over the last 2 and 6 years, respectively. Since he was mentally retarded and in a poor respiratory state, dental treatment under general anesthesia was scheduled in our hospital. General anesthesia was induced and maintained using 30% nitrous oxide and 1-3% sevoflurane in oxygen through the tracheotomy tube. Pre- and intraoperative endotracheal suction improved the condition of both lungs markedly and the procedures were uneventful and completed in 2 h and 58 min.

A Novel Locus for Ectodermal Dysplasia of Hairs, Nails and Teeth Type Maps to Chromosome 18q22.1–22.3

Ectodermal dysplasias (EDs) are developmental disorders affecting tissues of ectodermal origin including hair, nails, teeth and sweat glands. Ectodermal dysplasia of hair, nails and teeth is a rare type of congenital disorder characterized by sparse and thin hair, dystrophic finger-and toenails and missing and abnormal teeth. In an effort to understand the molecular basis of this form of ED a family of Pakistani origin with an autosomal recessive pattern of inheritance was ascertained from a remote region in Pakistan. The clinical features of the affected individuals included thin and fine hair on the scalp, dystrophic and flat nails, absent or sparse eyebrows and eyelashes, missing and abnormal teeth, and thin body hair. A human genome scan carried out using microsatellite markers mapped the disease locus in this family to chromosome 18q22.1-18q22.3. A maximum two-point LOD score of 2.73 (theta= 0.0) was obtained at marker D18S541. Multipoint linkage analysis resulted in a maximum LOD score of 3.42 obtained with several markers, including D18S1125, ATA82B02, D18S848, D18S488, D18S1091, and D18S485, which supported the linkage. The linkage interval is flanked by markers D18S857 and D18S815, which corresponds to a region of 17.32 cM according to Rutgers combined linkage and physical map (build 36). This region covers 8.63 Mb according to the sequence-based physical map. Three candidate genes, CDH7, CDH19 and ZNF407, from the linkage interval were sequenced and found to be negative for functional sequence variants. This study is the first step towards the identification of a gene involved in hair, nails and teeth type ED.

Further delineation of cardio-facio-cutaneous syndrome: clinical features of 38 individuals with proven mutations

Background:Cardio-facio-cutaneous syndrome (CFC) is a multiple congenital anomaly/mental retardation syndrome named because of a characteristic facies, cardiac anomalies, and ectodermal abnormalities. While considerable literature describes the main features, few studies...

Localization of a novel autosomal recessive hypotrichosis locus (LAH3) to chromosome 13q14.11–q21.32

Autosomal recessive hypotrichosis is a rare form of alopecia characterized by sparse hair on scalp, sparse to absent eyebrows and eyelashes, and sparse auxiliary and body hair. Previously, for this form of hypotrichosis, two loci LAH (localized hereditary hypotrichosis) and AH (autosomal recessive hereditary hypotrichosis) have been mapped on chromosome 18q12.1 and 3q27.2, respectively. In the study presented here, we report the localization of a third locus for autosomal recessive form of hypotrichosis in two large Pakistani families. The patients in the two families exhibited typical features of the hereditary hypotrichosis. Genome scan using polymorphic microsatellite markers mapped the gene on chromosome 13q14.11-q21.32. A maximum combined two-point logarithm of odds (LOD) score of 4.79 at theta= 0.0 was obtained for several markers. Multipoint linkage analysis resulted in a maximum LOD score of 5.9, which further supports the linkage. Haplotype analysis defined the linkage interval of 17.35 cM flanked by markers D13S325 and D13S1231 according to the Rutgers combined linkage-physical map. This region contains 24.41 Mb according to the build 36 of the human genome sequence-based physical map.

Atypical Rothmund-Thomson syndrome in a patient with compound Heterozygous Mutations in RECQL4 Gene and phenotypic features in RECQL4 syndromes

We describe the natural history of the RTSII phenotype in a 7-year-old boy who developed intrauterine and postnatal growth retardation, failure to thrive and persisting diarrhoea. The growth hormone stimulation test identified an isolated growth hormone deficiency. Since infancy, the patient manifested skin lesions characterized by a very mild poikilodermic-like appearance on the cheeks only, widespread café-au-lait spots and the absence of eyebrows and eyelashes. There was no cataract. Orthopaedic and radiologic work-up identified the absence of thumb anomaly and radial head luxation and patellar hypoplasia. Neurologic, cognitive milestones and intelligence were normal. The cytogenetic work-up did not show any anomaly. Based on this clinical presentation, we carried out a sequencing analysis of the RECQL4 gene, which is responsible for Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes and found a splice site mutation (IVS10-1G>A) and a nucleotide substitution in exon 12 (L638P). The mother was identified as a carrier for the substitution in exon 12 and the father for the splice site mutation, respectively. An analysis of the transcripts focused on the RECQL4 helicase domain: in the proband only those generated from the maternal L638 allele were present. This case report emphasizes the clinical overlap between RAPADILINO and Rothmund-Thomson syndromes within a continuum phenotypic spectrum. The distinctive set of clinical signs displayed by the patient may be accounted for by his unique combination of two different RECQL4 mutations. The molecular findings provide information that enhances our comprehension of genotype-phenotype correlations in RECQL4 diseases, enables a more precise genetic counseling to the parents and facilitates a more appropriate long-term follow-up to the affected child.

Cardio-Facio-Cutaneous Syndrome: Two Cases in the Same Generation

A 4-year-old Japanese boy, the youngest of three brothers, presented with ichthyosiform hyperkeratosis over his whole body, eczematous erythema with partial desquamation and erosion on the flexor side of the joints of extremities, the fossa axillaries, and the genital and buttock regions, and total hair loss on the scalp and the absence of eyebrows and eyelashes. In addition to the ichthyotic eruptions and hair abnormalities, he also had a ventricular septal defect, mental retardation, growth retardation, characteristic facial features such as a depressed nasal bridge, low-set ears, and ocular hypertelorism; therefore, he was diagnosed with cardio-facio-cutaneous (CFC) syndrome. The patient's family did not have a history of consanguineous marriage. The parents and the eldest son were healthy. However, the second son, also born with ichthyosiform hyperkeratosis over his whole body, total hair loss on the scalp, myocardial deficiency, mental retardation, growth retardation, and characteristic facial features, had died of pneumonia and sepsis at the age of 1.5 years. Because the middle brother had the same disease, the present case is considered to be a rare case of CFC syndrome with in a single generation.

Ablepharon‐macrostomia syndrome in a 46‐year‐old woman

Ablepharon-macrostomia syndrome (AMS) is a rare condition reported to date in 13 patients worldwide. AMS is characterized by absent or short eyelids, absent eyebrows and eyelashes, macrostomia, and external ear abnormalities. Additional features include alopecia or sparse hair, hypoplastic malar region, redundant skin, rudimentary nipples, abnormal genitalia. While the AMS phenotype is well delineated in infants and children, clinical manifestations are rather poorly characterized in adulthood. Here, we report on an Italian woman who received a diagnosis of AMS at the age of 46 years after several surgical treatments. A clinical comparison between our patient and previously reported AMS cases aids in delineating the adult phenotype of AMS and further broadens the clinical spectrum of this condition.

The role of eyebrows in face recognition.

A fundamental challenge in face recognition lies in determining which facial characteristics are important in the identification of faces. Several studies have indicated the significance of certain facial features in this regard, particularly internal ones such as the eyes and mouth. Surprisingly, however, one rather prominent facial feature has received little attention in this domain: the eyebrows. Past work has examined the role of eyebrows in emotional expression and nonverbal communication, as well as in facial aesthetics and sexual dimorphism. However, it has not been made clear whether the eyebrows play an important role in the identification of faces. Here, we report experimental results which suggest that for face recognition the eyebrows may be at least as influential as the eyes. Specifically, we find that the absence of eyebrows in familiar faces leads to a very large and significant disruption in recognition performance. In fact, a significantly greater decrement in face recognition is observed in the absence of eyebrows than in the absence of eyes. These results may have important implications for our understanding of the mechanisms of face recognition in humans as well as for the development of artificial face-recognition systems.

The gene for autosomal dominant hidrotic ectodermal dysplasia (Clouston syndrome) in a large Indian family maps to the 13q11-q12.1 pericentromeric region.

Hidrotic ectodermal dysplasia (HED), Clouston syndrome (MIM No. 129500), is an autosomal dominant disorder affecting the skin and its derivatives. It is characterized by alopecia, dysplastic nails in hands and feet, and hyperkeratosis of the palms and soles. We have studied a large Indian pedigree (UR005), from Gujarat region, consisting of a total 127 individuals including 41 affected (12 males and 29 females). The phenotype in this family ranged from atrichosis to hypotrichosis, sparsity or absence of eyebrows, and thickening of palms and soles. In order to map the disease locus by linkage analysis, DNA polymorphisms were used in DNAs from 23 affected and 8 normal individuals. While genotyping was in progress, Kibar et al. [1996] reported mapping of the locus of a similar disease in French-Canadian families to 13q around marker D13S141. We then utilized markers on 13q to genotype the members of the Indian family. Linkage with 13q11-12.1 markers was confirmed with a maximum lod score of 3.27 (theta=0.00) with locus D13S1316. Multipoint linkage analysis yielded a lod score of 5.04 at theta=0.00 with D13S1316; haplotype analysis indicated that the gene for the Clouston syndrome in this family is localized proximal to D13S292. These data suggest that the gene for the Clouston syndrome in this Indian pedigree is probably the same as that described in the French Canadian families. The combination of data from all available families linked to 13q11-12.1 will make it possible to narrow the critical region and facilitate the positional cloning of the elusive gene.