P2004Netherton syndrome

Curt Mafra Treu, MD, Policlinica Geral do Rio de Janeiro, Rio de Janeiro, Brazil;Luana Boeira Rocha, MD, Policlinica Geral do Rio de Janeiro, Rio de Janeiro,Brazil; Manuela Boleira Sieiro Guimaraes, MD, Policlinica Geral do Rio de Janeiro,Rio de Janeiro, Brazil; Paula Periquito Cosenza, MD, Policlı́nica Geral do Rio deJaneiro, Rio de Janeiro, Brazil

Background: Netherton syndrome is an autosomal recessive genodermatosis (5q32)of unknown cause. In its complete form is characterized by erythroderma, linearcircumflex ichthyosis, trichorrhexis invaginata, atopic diathesis, andhypodevelopment.

Case report: A 42-year-old man reported the appearance of erythematous papuleswith centrifugal growth, forming arciform lesions, some circinate with peel edges,various sizes, in the upper extremities, lower extremities, buttocks, palms, andsoles. The lesions were migratory, involuted spontaneously, and reemerged else-where over a period of approximately 2 to 3 months with eventual itching. He hadno comorbidities, denied smoking, the regular use of alcohol or drugs, and atopy. Hehad 19 previous nonspecific biopsies. He has a brother, also male, with similarclinical appearance, since 12 years of age. He had a previous treatment with topicalkeratolytics with partial resolution of his symptoms and oral acitretin withoutimprovement. VDRL, serology for HIV 1 and 2, also for HTLV-1, ANA and serum IgEwere negative. Diagnostic hypotheses: poroceratose, symmetric progressive eryth-rokeratodermia, linear circumflex ichthyosis, and erythrokeratodermia variabilis. Anew histologic examination was consistent with linear circumflex ichthyosis.

Discussion: In 1958, Netherton described a girl with generalized dermatitis peel anddeformities of nodular fragile hair shaft, which he called trichorrhexis nodosa(bamboo hair). This was later renamed appropriately as trichorrhexis invaginated, adeformity of the hair shaft of the ball and socket type, suggested by Wilkinson et al.Netherton syndrome is an autosomal recessive genodermatosis (5q32) of unknowncause. In its complete form, it is characterized by erythroderma inflammatorychanges; trichorrhexis invaginated (bamboo hair); linear circumflex ichthyosis;atopic diathesis; and hypodevelopment—the development returns to normal after 2years. Netherton syndrome has been described in all races, but is more common infemales. Its frequency is still unknown, probably because of the diagnostic difficulty.The most common complications are skin and systemic infections. The diagnosis isclinical and laboratory, the histologic finds are nonspecific. The response totreatment is unsatisfactory. Possible complications need to be treat with appropriateand effective therapeutic regimens. Emollients, keratolytics, and antibiotics are thecornerstones of treatment.

MARCH 2

cial support: None identified.

Commer

P2005A novel mutation in the GJB2 (connexin 26) gene in a child with clinicaland histologic features of keratitis-ichthyosis-deafness syndrome

Uffe Koppelhus MD, MD, PhD, Department of Dermatology, Aarhus UniversityHospital, Aarhus C, Denmark; Gitte Esberg, MD, Department of Pediatrics, SkejbyHospital, Aarhus University Hospital, Aarhus N, Denmark; Lisbeth Tranebjaerg,MD, PhD, Department of Audiology, Bispebjerg Hospital, Copenhagen NV,Denmark; Mette Ramsing, MD, PhD, Department of Pathology, AarhusUniversity Hospital, Aarhus, Denmark; Mette Sommerlund, MD, PhD,Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disor-der that is characterized by the presence of an atypical ichthyosiform erythrodermaassociated with congenital sensorineural deafness and vascularizing keratitis. KIDwas first described in 1915 and fewer than 100 cases have been reported so far. Thesyndrome is caused by a heterozygous missense mutation in GJB2 encoding the gapjunction protein connexin 26 (Cx26). The most frequent mutation is the p.D50Nmutation, but a few other mutations have been described. The mutations are mainlysporadic, but familial cases (approximately 30 %) have also been reported. Wheninherited, the mutation seems to follow an autosomal dominant pattern. We here,describe a new mutation p.A88V of the Cx26 gene, leading to KID syndrome. Adifferent missense mutation (p.A88S) has been described in heterozygosity in a deafchild, whose mother was also heterozygous carrier, but had normal hearing ability.The diagnosis KID syndrome was suspected from the clinical findings: hearing loss,ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar kerato-derma, and alopecia of the scalp and eyelashes. At birth, a thick vernix caseosa likecovering of the scalp was observed. Histologic analysis showed the characteristicpattern for KID syndrome with acanthosis and papillomatosis of the epidermis withbasket-weave hyperkeratosis. The boy was born prematurely (33 1 4), weighed3000g (ie, as large for his gestational age), and had Apgar scores 1/1, 5/3, and 9/10.He had intraventricular hemorrhage grade 1 to 2 and intracerebral bleeding anddeveloped hydrocephalus. The skin symptoms were treated successfully withacitretin (0.5mg/kg) in combination with intensive skin care resulting in a significantimprovement of the severe hyperkeratotic lesions within 4 to 5 days. However, thechild’s condition was further complicated by septicemia and meningeal infectionwith extended-spectrum beta-lactamase producing Klebsiella pneumoniae fol-lowed by severe respiratory impairment and death at 46 weeks of gestational age (13weeks postnatally).

cial support: None identified.

Commer

010

P2006Treatment of erythrokeratoderma variabilis with isotretinoin

Lyubov Avshalumova, DO, SunCoast Hospital/Largo Medical Center, Largo, FL,United States; Matthew Mahoney, MD, Mahoney Dermatology Specialists, Largo,FL, United States

Erythrokeratoderma variabilis (EKV), also known as Mendes da Costa syndrome, is arare, autosomal dominantly inherited disorder of keratinization. It has been shownto be associated with mutations in genes for gap junction proteins GJB3 (encodingconnexin 31) and GJB4 (encoding connexin 30.3). EKV usually presents within thefirst year of life, and has a chronic course. It is characterized by coexistenthyperkeratotic plaques and transient erythematous patches. Patients are otherwisehealthy with normal life expectancy. However, the psychosocial impact on life canbe tremendous in affected individuals. We describe a 12-year-old boy presentingwith generalized yellow-brown, thick, hyperkeratotic plaques. He also exhibitedsharply demarcated, arcuate and spiral-shaped erythematous and hypopigmentedpatches with fine scale, along with confluent palmar and plantar keratoderma.According to his mother, scaly red patches first appeared at 6 months of age, whichsubsequently evolved into thick plaques with geographic shapes at 5 years of age.The clinical picture was suggestive of EKV. The patient’s father had similar lesions inchildhood; however, his skin disease improved around the end of adolescence andhe now has less erythematous, pink hyperkeratotic plaques present over the kneesand elbows. Treatment with multiple topical agents, including urea and lactic acidcreams as well as tazarotene, was attempted without success. Patient was started ona course of isotretinoin at 20mg/day with some improvement noted within monthsof therapy. Tapering to 10mg/day, however, did not sustain the benefit and dose ofisotretinoin was again increased to 20mg/day. Monthly monitoring of the laboratoryvalues has not revealed any changes after 6 months of therapy, and the patient hasdenied side effects other than dry lips. The efficacy of systemic retinoids in disordersof keratinization is well documented in the literature. However, their use in childrenis limited because of concerns of serious adverse effects on musculoskeletal,neurologic, and gastrointestinal systems with chronic use. Low doses are ofteneffective in EKV. Patient education and close follow-up are essential to reduce therisk of potential complications. When used appropriately, systemic retinoids are safeand effective in pediatric population. They can minimize discomfort and signifi-cantly improve quality of life and social interactions in affected children.

cial support: None identified.

Commer

P2007Mutations in TRPS1 gene in tricho-rhino-phalangeal syndrome type I

Li-Hsuan Chen, MD, Department of Dermatology, National Cheng-KungUniversity Hospital, Tainan, Taiwan; Sheau-Chiou Chao, MD, Department ofDermatology, National Cheng-Kung University Hospital, Tainan, Taiwan

Background: The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) areautosomal dominant disorders characterized by craniofacial and skeletal abnormal-ities. They share common features, such as sparse and slow-growing scalp hair,laterally sparse eyebrows, bulbous pear-shaped nose, elongated and flat philtrum,thin upper lip, and protruding ears. Various skeletal abnormalities are also observed,including short stature, shortening of the phalanges and metacarpals, cone-shapedepiphyses, and Perthes-like change of the hips. The TRPS1 gene was first identifiedin 2000 and mapped to 8q24.1. The gene encodes a zinc-finger transcription factorand the mutations in it are responsible for TRPS.

Objectives: To examine clinically suspected cases of TRPS I for mutations in theTRPS1 gene.

Methods: Blood specimens were obtained from seven patients of TRPS I. DNApurification, PCR amplification, heteroduplex scanning by conformation-sensitivegel electrophoresis (CSGE), and automated nucleotide sequencing were performed.Then verification of the mutations was performed.

Results: Seven patients with the typical phenotype of TRPS I were included. Twocases showed familial inheritance, and the others were sporadic. Three nonsensemutations, including C2113T (Q705X), G2179T (E727X), and C1591T (R531X), andtwo frame shift mutations,1184delG and C1140TA, resulting in premature stopcodons were identified in five of the patients. We were not able to detect themutations in the rest two patients one of whom had familial inheritance.

Conclusions: If clinicians are aware of the disease, TRPS is readily recognizable fromthe clinical and radiologic features. Molecular analysis of the mutations underlyingTRPS is a viable and accessible means for diagnosis and future gene therapy. Furtherstudy will be needed to find out if there is another gene contributing to TRPS toexplain the absence of mutations in the two patients in the series.

cial support: None identified.

Commer

J AM ACAD DERMATOL AB71