ABSTRACT
BACKGROUND: Focal dermal hypoplasia (FDH) is rare X-linked dominant disease characterized by atrophy and linear pigmentation of the skin, split hand/foot deformities and ocular anomalies. FDH is caused by mutations of the Porcupine (PORCN) gene, which encodes an enzyme that catalyzes the palmitoylation of Wnt ligands required for their secretion. High resolution melting analysis (HRM) is a technique that allows rapid, labor-efficient, low-cost detection of genomic variants. In the present study, we report the successful implementation of HRM in the molecular diagnosis of FDH. METHODS: Polymerase chain reaction and HRM assays were designed and optimized for each of the coding exons of the PORCN gene, processing genomic DNA samples form a non-affected control and a patient complying with the FDH diagnostic criteria. The causal mutation was characterized by Sanger sequencing from an amplicon showing a HRM trace suggesting heterozygous variation and was validated using an amplification-refractory mutation system (ARMS) assay. RESULTS: The melting profiles suggested the presence of a variant in the patient within exon 1. Sanger sequencing revealed a previously unknown C to T transition replacing a glutamine codon for a premature stop codon at position 28, which was validated using ARMS. CONCLUSIONS: Next-generation sequencing facilitates the molecular diagnosis of monogenic disorders; however, its cost-benefit ratio is not optimal when a single, small or medium size causal gene is already identified and the clinical diagnostic presumption is strong. Under those conditions, as it is the case for FDH, HRM represents a cost- and labor-effective approach.
Subject(s)
Acyltransferases/genetics , Exons/genetics , Focal Dermal Hypoplasia/diagnosis , Focal Dermal Hypoplasia/genetics , Membrane Proteins/genetics , Nucleic Acid Denaturation/genetics , Amino Acid Sequence , Codon, Nonsense , Female , Focal Dermal Hypoplasia/physiopathology , Heterozygote , Humans , Infant , Mutation , Phylogeny , Polymerase Chain Reaction/methods , Sequence AlignmentSubject(s)
Abnormalities, Multiple , Focal Dermal Hypoplasia/diagnosis , Diagnosis, Differential , Humans , Infant , MaleABSTRACT
RESUMEN Introducción: El síndrome de Goltz o hipoplasia dérmica focal es una enfermedad genética rara del grupo de las displasias ectodérmicas con un mecanismo de herencia dominante ligado al cromosoma X. Objetivo: Describir las características clínicas del síndrome de Goltz, su diagnóstico y tratamiento. Presentación del caso: Paciente femenina de 4 años de edad diagnosticada con síndrome de Goltz. Se valora en equipo multidisciplinario con las especialidades de genética, cirugía maxilofacial, estomatología, dermatología, oftalmología, ortopedia y el servicio de otorrinolaringología. Conclusiones: El síndrome de Goltz se caracteriza principalmente por afectación cutánea; anomalías oculares, dentales, faciales y esqueléticas; afectación del aparato gastrointestinal, urinario, cardiovascular y sistema nervioso central con grado variable de severidad. Su diagnóstico es clínico. La atención interdisciplinaria es fundamental para el adecuado diagnóstico y tratamiento; su pronóstico depende del grado de afectación(AU)
ABSTRACT Introduction: Goltz syndrome also known as focal dermal hypoplasia is a rare genetic disease in the ectodermal dysplasia´s group and with a mechanism of dominant inheritance linked to the X chromosome. Objectives: To describe the clinical characteristics of the Goltz syndrome, its diagnosis and treatment. Case presentation: Case of a 4 year-old female patient diagnosed with Goltz syndrome. She was studied by a multidisciplinary team including Genetics, Maxillofacial Surgery, Stomatology, Dermatology, Ophthalmology, Orthopedics and ORL specialists. Conclusions: Goltz syndrome or focal dermal hypoplasia is mainly characterized by skin affectations; eyes, dental, skeletal, and face anomalies; gastrointestinal tract, urinary, cardiovascular and central nervous systems´ affections with varying degrees of severity. The diagnosis is clinical. A multidisciplinary approach is essential for a proper diagnosis and treatment; and prognosis depends on the grade of severity(AU)
Subject(s)
Humans , Female , Child, Preschool , Focal Dermal Hypoplasia/diagnosis , Focal Dermal Hypoplasia/genetics , Focal Dermal Hypoplasia/drug therapy , Focal Dermal Hypoplasia/diagnostic imaging , Case ReportsABSTRACT
Resumen: Introducción: La hipoplasia dérmica focal o síndrome de Goltz es una rara genodermatosis de herencia dominante ligada al X, que afecta al tejido proveniente de las placas del ectodermo y del mesodermo. El cuadro clínico se caracteriza por alteraciones cutáneas, oftálmicas, neurológicas, dentales, ungueales, bucales, de tejidos blandos y esqueléticas. El diagnóstico se realiza por los hallazgos clínicos en un individuo con alteraciones ectodérmicas y malformaciones características en las extremidades. El manejo es multidisciplinario y, al igual que el pronóstico, depende de las alteraciones específicas que presente cada paciente. Caso clínico: Se presenta el caso de un recién nacido de sexo femenino, de 15 días de vida, con zonas de alopecia en piel cabelluda, herniación de tejido celular subcutáneo en varias áreas de todos los segmentos corporales, escotadura en ala nasal, hendidura en encía superior, defecto grave de extremidad superior izquierda con rizomelia (acortamiento de segmento proximal) y aplasia de radio, así como ectrodactilia de miembro pélvico derecho. Todos los hallazgos son compatibles con hipoplasia dérmica focal de acuerdo con los criterios diagnósticos. Conclusiones: Se presenta el caso de una paciente recién nacida con síndrome de Goltz.
Abstract: Background: Focal dermal hypoplasia or Goltz syndrome is a rare X-linked dominant inherited genodermatosis, affecting both the ectodermal and mesodermal tissue. Clinical manifestations include skin abnormalities, defects in eyes, teeth, nails, mouth, soft tissues and skeleton. The diagnosis is based on clinical findings and is suspected in individuals with ectodermal abnormalities and characteristic malformations in the extremities. The management is multidisciplinary and, like the prognosis, depends on the specific alterations that each patient presents. Case report: We report the case of a 15-day-old female newborn with alopecic areas on the scalp, herniation of subcutaneous cellular tissue at the lumbar level, nasal wing notch, severe left superior limb defect with rhizomelia (proximal segment shortening) and radio aplasia, as well as right leg ectrodactyly, areas of atrophy compatible with focal dermal hypoplasia according to diagnostic criteria. Conclusions: We present a case of female newborn patient with Goltz syndrome.
Subject(s)
Female , Humans , Infant, Newborn , Focal Dermal Hypoplasia/diagnosis , Limb Deformities, Congenital/etiology , Prognosis , Focal Dermal Hypoplasia/physiopathologyABSTRACT
Background: Focal dermal hypoplasia or Goltz syndrome is a rare X-linked dominant inherited genodermatosis, affecting both the ectodermal and mesodermal tissue. Clinical manifestations include skin abnormalities, defects in eyes, teeth, nails, mouth, soft tissues and skeleton. The diagnosis is based on clinical findings and is suspected in individuals with ectodermal abnormalities and characteristic malformations in the extremities. The management is multidisciplinary and, like the prognosis, depends on the specific alterations that each patient presents. Case report: We report the case of a 15-day-old female newborn with alopecic areas on the scalp, herniation of subcutaneous cellular tissue at the lumbar level, nasal wing notch, severe left superior limb defect with rhizomelia (proximal segment shortening) and radio aplasia, as well as right leg ectrodactyly, areas of atrophy compatible with focal dermal hypoplasia according to diagnostic criteria. Conclusions: We present a case of female newborn patient with Goltz syndrome.
Introducción: La hipoplasia dérmica focal o síndrome de Goltz es una rara genodermatosis de herencia dominante ligada al X, que afecta al tejido proveniente de las placas del ectodermo y del mesodermo. El cuadro clínico se caracteriza por alteraciones cutáneas, oftálmicas, neurológicas, dentales, ungueales, bucales, de tejidos blandos y esqueléticas. El diagnóstico se realiza por los hallazgos clínicos en un individuo con alteraciones ectodérmicas y malformaciones características en las extremidades. El manejo es multidisciplinario y, al igual que el pronóstico, depende de las alteraciones específicas que presente cada paciente. Caso clínico: Se presenta el caso de un recién nacido de sexo femenino, de 15 días de vida, con zonas de alopecia en piel cabelluda, herniación de tejido celular subcutáneo en varias áreas de todos los segmentos corporales, escotadura en ala nasal, hendidura en encía superior, defecto grave de extremidad superior izquierda con rizomelia (acortamiento de segmento proximal) y aplasia de radio, así como ectrodactilia de miembro pélvico derecho. Todos los hallazgos son compatibles con hipoplasia dérmica focal de acuerdo con los criterios diagnósticos. Conclusiones: Se presenta el caso de una paciente recién nacida con síndrome de Goltz.
Subject(s)
Focal Dermal Hypoplasia/diagnosis , Limb Deformities, Congenital/etiology , Female , Focal Dermal Hypoplasia/physiopathology , Humans , Infant, Newborn , PrognosisABSTRACT
El síndrome de Goltz, o hipoplasia dérmica focal, es un desorden multisistémico raro que involucra la piel, el sistema músculo-esquelético, los ojos, el pelo, las uñas y el riñón, entre otros, con considerable variación en los rasgos clínicos. El examen oftalmológico del caso que se presenta corresponde a una niña con microftalmia en el ojo izquierdo, obstrucción del conducto nasolagrimal en el ojo derecho y coloboma de iris y del nervio óptico del ojo microftálmico, además de esotropia sensorial. El diagnóstico fue confirmado por genética como una hipoplasia dérmica focal que, a pesar de ser poco común, debemos conocerlo para poderlo identificar si se presentara en nuestra consulta(AU)
Goltz syndrome or focal dermal hypoplasia is a rare multisystemic disorder involving the skin, the musculoskeletal system, the eyes, the hair, the nails and the kidney among others, with considerable variation in clinical features. The ophthalmological examination of the case presented in this paper shows a girl who has microphthalmia in the left eye, nasolacrimal duct obstruction in the right eye and coloboma of the iris and optic nerve in the microphthalmic eye in addition to sensory esotropia. The diagnosis was confirmed by genetic studies and it was focal dermal hypoplasia, which is a rare disease but we should learn about it to be able to identify it if some patient with the disease goes to our service(AU)
Subject(s)
Humans , Female , Infant , Esotropia/diagnosis , Focal Dermal Hypoplasia/diagnosis , Microphthalmos/diagnosis , Nasolacrimal Duct/abnormalitiesABSTRACT
Focal dermal hypoplasia or Goltz syndrome is a rare X-linked genodermatosis characterized by cutaneous and musculoskeletal defects. Dermoscopy is a noninvasive auxiliary method for the diagnosis of lesions, whether melanocytic or not. Its widespread use in dermatology is resulting in the description of new patterns and characterization of lesions not reported before its use. A typical case of Goltz syndrome presenting multiple malformations was observed and submitted to dermoscopy. Dermoscopy findings of the papillomas in raspberry form in the perioral and ocular regions, revealed a unique vascular pattern, different from viral warts; dermoscopy of some brownish maculas resembling lentigo in the periphery of skin atrophic areas are described as lentigo-like lesions, an uncommon pattern of melanocytic lesions, but without criteria suggestive of malignancy.
Subject(s)
Dermoscopy , Focal Dermal Hypoplasia/diagnosis , Female , Focal Dermal Hypoplasia/pathology , Humans , Young AdultABSTRACT
Focal dermal hypoplasia (FDH), also known as Goltz-Gorlin syndrome, is an autosomal dominant disease affecting tissues derived from the ectoderm and mesoderm. Knowledge and early diagnosis of the craniofacial alterations commonly found in patients with FDH provide oral health care professionals with effective preventive and therapeutic tools. This article aims to review the craniofacial characteristics present in FDH and the main systemic manifestations that have implications for dental management, while presenting a new case of the syndrome with novel oral findings.
Subject(s)
Craniofacial Abnormalities/diagnosis , Focal Dermal Hypoplasia/diagnosis , Tooth Abnormalities/diagnosis , Anodontia/diagnosis , Child, Preschool , Cuspid/abnormalities , Dental Care for Chronically Ill , Dental Enamel Hypoplasia/diagnosis , Early Diagnosis , Facial Asymmetry/diagnosis , Female , Follow-Up Studies , Humans , Incisor/abnormalities , Labial Frenum/abnormalities , Molar/abnormalities , Palate, Hard/abnormalities , Tooth Eruption, Ectopic/diagnosisABSTRACT
Goltz syndrome is a rare genetic disease of X-linked dominant inheritance. It is more common in female patients and, in most cases, results in miscarriage of male fetuses. It has a broad scope of possible clinical manifestations. Its diagnosis consists of the sum of the many clinical, radiological and histopathological findings. The treatment options are genetic counseling, reconstructive surgery and multidisciplinary approach, aiming to improve quality of life and ensure a normal and productive life.
Subject(s)
Abnormalities, Multiple/diagnosis , Focal Dermal Hypoplasia/diagnosis , Abnormalities, Multiple/genetics , Adolescent , Female , Focal Dermal Hypoplasia/genetics , Humans , SyndromeABSTRACT
A síndrome de Goltz é uma doença genética rara, de herança dominante ligada ao X, mais comum em doentes do sexo feminino e, na maioria das vezes, resulta no aborto dos fetos do sexo masculino. Tem um amplo espectro de manifestações clínicas possíveis. O diagnóstico consiste no somatório dos numerosos achados clínicos, radiológicos e histopatológicos. O tratamento é o aconselhamento genético, cirurgias reconstrutivas e abordagem multidisciplinar, com objetivo de melhorar a qualidade de vida e garantir uma vida normal e produtiva.
Goltz syndrome is a rare genetic disease of X-linked dominant inheritance. It is more common in female patients and, in most cases, results in miscarriage of male fetuses. It has a broad scope of possible clinical manifestations. Its diagnosis consists of the sum of the many clinical, radiological and histopathological findings. The treatment options are genetic counseling, reconstructive surgery and multidisciplinary approach, aiming to improve quality of life and ensure a normal and productive life.
Subject(s)
Adolescent , Female , Humans , Abnormalities, Multiple/diagnosis , Focal Dermal Hypoplasia/diagnosis , Abnormalities, Multiple/genetics , Focal Dermal Hypoplasia/genetics , SyndromeABSTRACT
Focal dermal hypoplasia or Goltz syndrome is a rare congenital and mesoectodermal dysplasia with multisystemic involvement. Although the genetic alterations responsible for focal dermal hypoplasia are not fully known, there is predominance in affected females, suggesting dominant X-linked inheritance. Besides the skin, other structures frequently involved are the skeletal system, eyes, teeth, hair, and nails. Skeletal abnormalities are predominantly observed in the hands and feet. We report a 9-year-old girl who had typical linear skin atrophy on the trunk, exuberant "fat herniations," several skeletal abnormalities, and exuberant "lobster claw" deformity. In addition, she had the typical longitudinal striations in femur metaphyses. With regard to family history, her mother had one male stillbirth with several deformities. This typical focal dermal hypoplasia patient is considered valuable in light of the affected male stillbirth and parents with nonaffected phenotypes that together provides evidence for mother-to-daughter spontaneous transmission.
Subject(s)
Focal Dermal Hypoplasia/diagnosis , Child , Female , Focal Dermal Hypoplasia/genetics , Humans , Infectious Disease Transmission, Vertical , SyndromeABSTRACT
Presentamos una paciente de un año y medio de edad con manifestaciones clínicas de hipoplasia dérmica focal (síndrome de Goltz), las cuales se confirmaron con el estudio histológico. Realizamos una revisión de la literatura referente a la enfermedad
Subject(s)
Humans , Female , Infant , Focal Dermal Hypoplasia/diagnosis , Diagnosis, Differential , Focal Dermal Hypoplasia/complications , Focal Dermal Hypoplasia/therapy , Syndactyly/etiology , X Chromosome/pathologyABSTRACT
Presentamos una paciente de un año y medio de edad con manifestaciones clínicas de hipoplasia dérmica focal (síndrome de Goltz), las cuales se confirmaron con el estudio histológico. Realizamos una revisión de la literatura referente a la enfermedad (AU)
Subject(s)
Humans , Female , Infant , Focal Dermal Hypoplasia/diagnosis , Focal Dermal Hypoplasia/therapy , Focal Dermal Hypoplasia/complications , Syndactyly/etiology , Diagnosis, Differential , X Chromosome/pathologyABSTRACT
Se describen tres casos de nevus lipomatoso superficial de Hoffman y Zurhelle vistos en los últimos 25 años en el Servicio de Dermatología del Hospital José Joaquín Aguirre. La edad de aparición de las lesiones estuvo entre 0 y 14 años de edad; fueron lesiones salientes del color de la piel, agrupadas o de disposición lineal, sésiles o pediculadas y asintomáticas, y en el examen histológico de los tres se ve tejido adiposo maduro normotípico en la dermis superficial rodeando las estructuras vasculares. El principal diagnóstico diferencial es la hipoplasia dérmica focal o síndrome de Goltz, aunque en nevi melanocíticos intradérmicos y en fribromas blandos de gran tamaño es frecuente encontrar también tejido adiposo en la dermis
Subject(s)
Female , Adolescent , Adult , Hamartoma/diagnosis , Neoplasms, Connective Tissue/diagnosis , Buttocks , Diagnosis, Differential , Focal Dermal Hypoplasia/diagnosis , Lumbosacral RegionABSTRACT
El síndrome de Goltz es una genodermatosis poco frecuente, caracterizada por displasia múltiple ectomesodérmica, en la que se encuentra, además, falla del desarrollo y malformaciones en la piel, tejidos blandos, sistema óseo ocular y dental. Se observa más en mujeres que en varones, ya que estos últimos padecen generalmente lesiones graves incompatibles con la vida. En este artículo describimos el caso de una paciente de 12 años de edad, cuya historia, examen clínico e histopatológico de las lesiones corresponden a este síndrome
Subject(s)
Humans , Female , Focal Dermal Hypoplasia/diagnosis , Focal Dermal Hypoplasia , Focal Dermal Hypoplasia/therapy , Signs and SymptomsABSTRACT
Se describe el caso clinìco de un paciente portador de un sindrome de Poland asociado a hipoplasia costal y dextrocardia. La Importancia de presentar este caso radica en la escasa frecuencia de presentaciòn de esta patologia. Se aprovecha el tema para realizar una actualizaciòn sobre este sindrome
Subject(s)
Humans , Male , Female , Infant, Newborn , Congenital Abnormalities/diagnosis , Dextrocardia/diagnosis , Poland Syndrome/diagnosis , Thoracic Diseases/diagnosis , Focal Dermal Hypoplasia/diagnosisABSTRACT
Descreve-se o caso de uma menina de sete anos com múltiplos defeitos congênitos de origem mesoectodérmica, sendo evidenciadas alteraçöes significativas do esqueleto, estruturas dentárias e oculares, tecidos moles e pele, as quais caracterizam a hipoplasia dérmica focal (síndrome de Goltz). Além dos exames clínico e dermatológico, foram feitas avaliaçöes oftalmológica, odontológica, ortopédica, otorrinolaringológica, estudos radiológicos e genéticos e exames bioquímicos e histopatológicos. Trata-se de uma síndrome rara, descrita pela primeira vez em 1962