Pitfalls in Clinical Diagnosis of Female Carriers of X-linked Hypohidrotic Ectodermal Dysplasia

Vincent, Marie-Claire

doi:10.1001/archderm.138.9.1256

Cited by 7 publications

(4 citation statements)

References 5 publications

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“…Generally, the starch‐iodine test detects heterozygous carriers with mild manifestations (4). However, the mutation search has to be considered a first‐line diagnostic test to detect asymptomatic carriers (5).…”

Section: Discussionmentioning

confidence: 99%

V‐Shaped Hyperpigmented Linear Lesions, Patchy Hypotrichosis, and Teeth Abnormalities in a Young Girl

Toll

Vincent

Calvas

2007

Pediatric Dermatology

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A 22-year-old woman presented to our Department complaining of linear hypopigmented lesions on the trunk and extremities as well as mild patchy hypotrichosis on the occipital area since infancy. Her medical history was significant for congenital dental abnormalities (hypodontia with conical-shaped teeth) that had been treated with orthodontic management and dental implants (Fig. 1). No consanguinity or similar abnormalities were recorded in the family.The patient described generalized xerosis and was aware of having hyperpigmented linear areas that were more visible after suntanning. She did not complain of reduced sweating.Physical examination revealed a fair-haired woman with scanty fine hair and an irregularly shaped occipital area of hypothrichosis. In the abnormal zone, the hair was thin and brittle with a whorly implantation (Fig. 2). Discrete eyebrow hypothrichosis was also noted. Linear hypopigmented streaks following a V-shaped pattern, intermingled with areas of normal skin, were observed on her back (Fig. 3). In addition, after a close examination, a patchy absence of vellus hair and stripes of hypotrichosis along the limbs were noted. No associated nail abnormalities were detected. A skin biopsy specimen taken from the transitional lines showed a segmental loss of eccrine sweat glands. WHAT SYNDROME IS THIS?Expression mosaicism of X-linked hypohidrotic ectodermal dysplasia. ADDITIONAL STUDIESA starch-iodine test was performed on the patient's back, demonstrating a linear distribution of nonfunctioning sweat glands along Blaschko lines (Fig. 4). Active sweat pores were evidenced by the appearance of minute dark spots. Genetic StudyMutation analysis of the ED1 gene from genomic DNA was performed in our patient. After direct DNA sequencing, a 8-bp duplication in exon 1 of ED1 gene [c.64_71dup8] resulting in a frameshift and premature stop codon [p.Cys25AlafsX34] was demonstrated.

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Section: Discussionmentioning

confidence: 99%

V‐Shaped Hyperpigmented Linear Lesions, Patchy Hypotrichosis, and Teeth Abnormalities in a Young Girl

Toll

Vincent

Calvas

2007

Pediatric Dermatology

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“…Kira-kira 30% tidak menunjukkan manifestasi klinis. 19 Starchiodine test dan biopsi kulit dapat membantu mendeteksi adanya perempuan pembawa gen mutan. 11,13 Kasus ini adalah seorang anak laki-laki dengan riwayat keluarga diduga pamannya juga menderita DEH.…”

Section: Diskusiunclassified

Displasia Ektodermal Hipohidrotik

Pn¹,

Hadinegoro

Boediardja³

2016

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Seorang bayi laki-laki berusia 4 bulan menderita displasia ektodermal hipohidrotik (DEH),merupakan kelainan genetik yang sebagian besar diturunkan secara x-linked recessive.Sindrom ini ditandai dengan tidak ada atau berkurangnya kelenjar keringat,hypotrichosis,dan hypodontia. Diagnosis ditegakkan berdasarkan gejala klinis dan dipastikandengan biopsi kulit yang menunjukkan tidak ada atau hipoplasi kelenjar ekskrin danrambut. Trias gambaran klinis utama DEH adalah hipohidrosis atau anhidrosis, hipotrikosisdan andontia total atau partial. Kelainan ini perlu segera ditegakkan untuk menghindarikomplikasi yang berat pada masa bayi dan diperlukan untuk menentukan penangananselanjutnya. Untuk mengetahui pola penurunan genetik pada pasien ini perlu disusunsilsilah penyakit dalam keluarga serta biopsi kulit atau uji starch-iodine pada kedua orangtua pasien sehingga konseling genetik. Pencegahan dapat diberikan secara multidisiplinsangat diperlukan dalam penanganan kasus seperti ini agar mendapatkan prognosis yanglebih baik. Displasia ektodermal hipohidrotik yang disebut juga Christ-Siemens Tourainesyndrome atau displasia ektodermal anhidrotik digambarkan pertama kali pada tahun 1848oleh Thurnam 1,2 dan diikuti pada abad-19 oleh Darwin.2 Pada tahun 1921, Thadanimenetapkan DEH sebagai suatu kelainan x-linked dan kemudian melaporkan bahwaperempuan pembawa gen mutan menampakkan gejala yang bervariasi dari kondisitersebut.1,2Angka kejadian DEH diperkirakan 1 per 100.000 kelahiran hidup,2,5 lebih 90% terjadi padaanak laki-laki.2 Di Indonesia dilaporkan 2 kasus pada tahun 2000-2002,6 salah satu kasusberobat di Subbagian Kulit Anak Ilmu Penyakit Kulit dan Kelamin FKUI-RSCM.

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“…The mother of patient 1 had no symptoms except for slightly decreased sweating, with X-chromosome inactivation being skewed mainly toward the normal allele in blood cells. Carriers who are heterozygous for an XLHED mutation may have variable clinical features (14,17,31,32). Lexner et al (17) reported that in two female carriers with pronounced clinical symptoms, the normal allele in their blood cells was mainly inactivated.…”

Section: Mutationsmentioning

confidence: 99%

Two Novel Mutations in the ED1 Gene in Japanese Families With X-Linked Hypohidrotic Ectodermal Dysplasia

et al. 2009

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X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by hypodontia, hypotrichosis, and hypohidrosis, is caused by mutations in ED1, the gene encoding ectodysplasin-A (EDA). This protein belongs to the tumor necrosis factor ligand superfamily. We analyzed ED1 in two Japanese patients with XLHED. In patient 1, we identified a 4-nucleotide insertion, c.119-120insTGTG, in exon 1, which led to a frameshift mutation starting from that point (p.L40fsX100). The patient's mother was heterozygous for this mutation. In patient 2, we identified a novel missense mutation, c.1141GϾC, in exon 9, which led to a substitution of glycine with arginine in the TNFL domain of EDA (p.G381R). This patient's mother and siblings showed neither symptoms nor ED1 mutations, so this mutation was believed to be a de novo mutation in maternal germline cells. According to molecular simulation analysis of protein structure and electrostatic surface, p.G381R increases the distance between K375 in monomer A and K327 in monomer B, which suggests an alteration of overall structure of EDA. Thus, we identified two novel mutations, p.L40fsX100 and p.G381R, in ED1 of two XLHED patients. Simulation analysis suggested that the p.G381R mutation hampers binding of EDA to its receptor via alteration of overall EDA structure. (Pediatr Res 65: 453-457, 2009) H ypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by the impaired development of teeth (hypodontia), hair (hypotrichosis), and eccrine sweat glands (hypohidrosis) (1). Most HED patients have shown an X-linked inheritance pattern, although a minority of patients had an autosomal dominant or recessive trait (2,3).The ED1 gene responsible for XLHED was mapped to chromosome Xq12-q13 and was identified by positional cloning (4). ED1 encodes the protein ectodysplasin-A (EDA) that belongs to the tumor necrosis factor ligand (TNFL) superfamily (5,6). EDA consists of a small N-terminal intracellular domain, a transmembrane domain, and a larger C-terminal extracellular domain containing a furin-cleavage site, a collagen-like domain, and a TNFL domain. The collagen-like domain has been believed to be necessary for trimerization of EDA proteins (7). However, it is not known whether the collagen-like domain is solely responsible for the trimerization: constructs of EDA-A1 and EDA-A2 lacking the collagenlike region can pack in the crystals as dimers of trimers (8). The TNFL domain has the ability to interact with the EDA receptor (EDAR) and X-linked ectodysplasin-A2 receptor (XEDAR) (9).EDA-A1 and EDA-A2 are the longest EDA isoforms, but they differ by only an insertion/deletion of two amino acids (E308, V309) as determined by alternative splicing of ED1 pre-mRNA. This insertion/deletion functions to regulate receptor-binding specificity, such that EDA-A1 binds EDAR, whereas EDA-A2 binds XEDAR (10). EDAR interacts with its adapter EDAR-associated death domain (EDARADD) to build an intracellular complex and activate the nuclear factor-B pathway, which is essen...

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Pitfalls in Clinical Diagnosis of Female Carriers of X-linked Hypohidrotic Ectodermal Dysplasia

Cited by 7 publications

References 5 publications

V‐Shaped Hyperpigmented Linear Lesions, Patchy Hypotrichosis, and Teeth Abnormalities in a Young Girl

V‐Shaped Hyperpigmented Linear Lesions, Patchy Hypotrichosis, and Teeth Abnormalities in a Young Girl

Displasia Ektodermal Hipohidrotik

Two Novel Mutations in the ED1 Gene in Japanese Families With X-Linked Hypohidrotic Ectodermal Dysplasia

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