Case and Research Letters
Congenital Absence of Nails and Digital-Type Thumb due to Prenatal Phenytoin Exposure
Ausencia congénita de uñas y pulgar digitalizado debida a la exposición prenatal a fenitoína
M. Karbhari Pawar
, V. Zawar
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Departamento de Dermatología, The Skin Clinic and Cosmetic Centre, Nashik, India
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"apellidos" => "Zawar" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Dermatología, The Skin Clinic and Cosmetic Centre, Nashik, India" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ausencia congénita de uñas y pulgar digitalizado debida a la exposición prenatal a fenitoína" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 599 "Ancho" => 755 "Tamanyo" => 65830 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Complete absence of nails of little and ring finger of the right hand with flexion deformity of the middle finger.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Anonychia i.e. absence of nails constitutes one of the component of limb anomalies in Fetal hydantoin syndrome (FHS), apart from the hypoplastic fingernails and distal phalanges, a digital-type thumb i.e. long, slender finger like-thumb, abnormal palmar creases, increased frequency of low arch, digital dermal ridge patterns and hip dislocation.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a>Craniofacial anomalies, ocular defects, and growth abnormalities are the other systemic manifestations of the FHS; however isolated simple anonychia i.e. absence of fingernails and toenails, without other congenital anomaly and slender, finger-like thumb is an extremely rare finding of FHS.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case Report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 15-year-old boy, otherwise healthy presented with absence of nails of both hands’ ring fingers and little fingers and both feet's 5<span class="elsevierStyleSup">th</span> toenails and hypoplastic nails of the 2<span class="elsevierStyleSup">nd</span>, 3<span class="elsevierStyleSup">rd</span> and 4<span class="elsevierStyleSup">th</span> toes<span class="elsevierStyleCrossOut">,</span> since birth (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). He was born of non-consanguineous marriage. His mother was suffering from epilepsy and was prescribed oral phenytoin 100<span class="elsevierStyleHsp" style=""></span>mg three times daily since her 20 years of age. Phenytoin was continued throughout her pregnancy and drug levels were not monitored. Along with phenytoin, folic acid 5<span class="elsevierStyleHsp" style=""></span>mg once daily was prescribed to the patient. Patient's past and family history was insignificant and his sibling didn’t suffer from any anomalies. He was of normal intelligence. On examination there was also flexion deformities of the distal interphalangeal joints and slight extension of his proximal interphalangeal joints of the left middle and ring finger and right middle finger (<a class="elsevierStyleCrossRefs" href="#fig0010">Figures 2 and 3</a>). His thumbs were thinner than the normal. Rest of his general and systemic examination was insignificant. Laboratory investigations including metabolic profile, Vitamin D and parathyroid hormone levels were within normal limits. Radiographic survey of the hands and feet were normal. Patient was counseled regarding benign nature of anonychia.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Meadow initially described a possible link between congenital abnormalities and maternal use of anticonvulsive drug in 1968 and it was expanded by Hanson and Smith in 1975 in the offspring of women taking phenytoin and they proposed these specific phenytoin related anomalies as FHS. FHS equally affects males and females. The incidence of complete classic FHS is around 5–10%, whereas one third (33%) of patients manifest an incomplete clinical syndrome. Women with mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are at major risk of having an infant with FHS.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Congenital isolated, non-syndromic anonychia results from mutation in the gene coding for R-spondin 4, which play a role in the Wnt signalling pathway. Syndromic form of anonychia presents with ectodermal dysplasia, skeletal or neurological malformations such as microcephaly, brachydactyly (Cooks syndrome), abnormal dentition, lymphedema, gingival fibromatosis (Zimmermannn–Laband syndrome), deafness, Iso–Kikuchi syndrome, Nail-patella syndrome and mental retardation (DOOR syndrome -deafness, onycho-osteodystrophy, mental retardation).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Coffin-Siris syndrome constitutes many features similar to FHS, such as hypoplastic fingernails and toenails (especially of the fifth finger); but severe mental retardation, joint laxity and dislocation of the radial head is present in Coffin-Siris syndrome.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Acquired causes of anonychia include trauma, pemphigus, lichen planus, Stevens–Johnson syndrome, epidermolysis bullosa, teratogens (drugs and alcohol), amniotic bands and viral infection during pregnancy.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Anonychia secondary to teratogenic drugs commonly occurs with phenytoin and warfarin and has also been reported with valproate, carbamazepine, morphine and trimethadone.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Nail development begins as flat rectangular surface of the future nail bed on the dorsal tips demarcated by folds, visible at 8-10 weeks of gestational age and is completed by the fifth month of gestational age; hence intake of teratogens by mother during the first and second trimester of pregnancy adversely affect nail development.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The exact mechanism of nail malformation is unknown but it is speculated that intermediate metabolites of phenytoin i.e. epoxides are responsible for its teratogenicity. Epoxides bind to embryonic or fetal nucleic acids, proteins and lipids and disrupt the normal development of the fetus at critical periods of embryogenesis. Also, co-oxidation of the phenytoin to free radical intermediates by prostaglandin synthetase may result in oxidant stress, which further initiate lipid peroxidation reactions and/or bind covalently to essential nucleic acids causing fetal dysmorphogenesis. Genetic make-up of the individual in-formation of these intermediate metabolites and free radicals and its clearance and repair mechanisms may explain different susceptibility across individuals.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5–7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Treatment of the hypoplastic nails is rarely indicated as their appearance may improve with time. Nail anomalies in a newborn may be a marker of increased maternal serum phenytoin concentration and it may herald more severe congenital abnormalities, especially mental retardation. As the teratogenic effect of the phenytoin is dose dependent, it is prudent to monitor drug levels regularly during the pregnancy.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of Interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case Report" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of Interest" ] 3 => array:1 [ "titulo" => "Bibliografía" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pawar MK, Zawar V. Ausencia congénita de uñas y pulgar digitalizado debida a la exposición prenatal a fenitoína. Eczema y urticaria en Portugal. 2019;110:778–780.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 424 "Ancho" => 805 "Tamanyo" => 65253 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Total absence of nails of 5<span class="elsevierStyleSup">th</span> toes.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 599 "Ancho" => 755 "Tamanyo" => 65830 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Complete absence of nails of little and ring finger of the right hand with flexion deformity of the middle finger.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 625 "Ancho" => 755 "Tamanyo" => 71904 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Anonychia of the ring and little finger of the left hand with flexion deformity of the middle and ring finger.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hand abnormalities in the fetal hydantoin syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L. 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| 2024 Noviembre | 30 | 14 | 44 |
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| 2023 Septiembre | 179 | 39 | 218 |
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