A de novo mutation in the PORCN gene in a newborn with Goltz syndrome / 中华皮肤科杂志

Objective:To report a newborn with Goltz syndrome and a de novo mutation in the PORCN gene. Methods:Clinical data collected from a newborn with Goltz syndrome were retrospectively analyzed. Peripheral venous blood samples were obtained from the newborn and her parents, genomic DNA was extracted, whole-exome sequencing was performed to screen disease-causing genes in the patient, and Sanger sequencing was conducted to verify the mutant genes.Results:The 7-hour-old female newborn presented with scalp defects, multiple epidermal defects on the face and inner side of both knee joints, deformity of the left auricle, syndactyly of the middle and ring fingers of the right hand as well as the great and second toes of the right foot, and lobster-claw deformity of the left foot. Genetic testing showed that a fragment TCCTTCCA was inserted at position 514-521 in exon 4 of the PORCN gene of the patient (c.514_521dupTCCTTCCA) , resulting in the substitution of serine by proline at amino acid position 175 (p.S175Pfs*14) , followed by translation termination at the 14th codon. This heterozygous mutation was not found in her parents. The patient was diagnosed with Goltz syndrome. Conclusions:There are various phenotypes of Goltz syndrome, and a confirmed diagnosis of Goltz syndrome can be made based on PORCN gene mutations and clinical manifestations. The heterozygous mutation c.514_521dupTCCTTCCA is a novel mutation.

Síndrome de Goltz o Hipoplasia dérmica focal / Goltz Syndrome or focal dermal hypoplasia

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)

Hipoplasia dérmica focal (síndrome de Goltz) / Focal dermal hypoplasia (Goltz syndrome)

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.

Focal dermal hypoplasia in a male neonate: a case report and literature review / 中华围产医学杂志

Objective To investigate the clinical and genetic characteristics of focal dermal hypoplasia (FDH) in children. Methods Clinical data, relevant examinations, histopathological features and genetic test results of a male newborn with FDH who was admitted to the neonatal ward of Beijing Children's Hospital of Capital Medical University were retrospectively analyzed. Reports of pediatric FDH patients with complete clinical data were retrieved from PubMed, Wanfang database and China National Knowledge Infrastructure from the establishment of these databases to March 2018 and characteristics of FDH was summarized. Results The case we reported here was a male neonate diagnosed with FDH in China, who was born with microcephaly, bilateral auricular cartilage dysplasia, tooth germ dysplasia and bipedal deformity and his skin, bone, gingiva, bilateral iris and pupils were all involved. Histopathological examination of the skin suggested dermal dysplasia. Genetic analysis showed a suspected chimeric nucleotide variation in PORCN gene (c.268 C>T), whereas no abnormalities were found in his parents and sister. A total of 60 cases (including the one we reported) of FDH diagnosed in childhood were reviewed, and 19 of them were confirmed in neonatal period. Fifty-seven of the 60 cases (95.0%) developed typical skin dysplasia and 56 cases (93.3%) with skeletal malformations, while other clinical manifestations vary. Histopathological examination suggested as dermis dysplasia, adipose tissue migration and reduction of appendage and collagen fibers. Among the 60 children, 19 (including four onset at neonatal period) underwent genetic testing and the results indicated PORCN gene mutation. Mutations in the four with neonatal-onset were c.956dupA, c.1061T>C, c.749C>T and c.268C>T. As the reported case was a boy, with only one X chromosome, the PORCN gene mutation could directly affected its function resulting in the abnormal phenotype. It was a de novo mutation as the same mutation was not detected in his parents. Conclusions FDH is a hereditary disease involving multiple systems with various clinical manifestations. Skin histopathological examination and genetic testing should be performed as soon as possible for early diagnosis and intervention. Accurate diagnosis is essential for genetic counseling, reproductive planning, prospective guidance and prognosis.

Gene mutation analysis of congenital skin defects: a case report / 中华皮肤科杂志

A female infant presented with skin defects and blisters for 2 hours after birth.Physical examination showed asymmetric skin defects on both lower extremities and left wrist,a thin-walled blister on the dorsal side of the right hand,and partial loss of the oral mucosa.No other abnormal signs were found.Genetic testing showed a heterozygous pathogenic mutation c.481C ＞ T (p.Gln161*) in exon 4 of the COL7A1 (NM-000094) gene and a heterozygous pathogenic mutation c.1837C ＞ T (p.Arg613*) in exon 14 of the COL7A1 (NM-000094) gene,which were also identified in the patient's father and mother respectively.The infant was diagnosed with congenital skin defects.The patient received protective isolation,focal washing with 0.9％ sodium chloride physiological solution,topical epidermal growth factor and comprehensive treatment for infection prevention.After 6-day treatment,the patient was discharged with dry and non-exudative skin lesions.This case prompted that abnormal heterozygosis mutation at C.481 and C.1837 sites on the COL7A1 (NM-000094) gene could form compound heterozygote,acting as pathogenic mutation.

Almost Unilateral Focal Dermal Hypoplasia

Focal dermal hypoplasia, caused by mutations in PORCN, is an X-linked ectodermal dysplasia, also known as Goltz syndrome. Only seven cases of unilateral or almost unilateral focal dermal hypoplasia have been reported in the English literature and there have been no previously reported cases in the Republic of Korea. A 19-year-old female presented with scalp defects, skin lesions on the right leg and the right trunk, and syndactyly of the right fourth and fifth toes. Cutaneous examination revealed multiple atrophic plaques and a brown and yellow mass with fat herniation and telangiectasia that was mostly located on the lower right leg. She had syndactyly on the right foot and the scalp lesion appeared to be an atrophic, membranous, fibrotic alopecic scar. A biopsy of the calf revealed upper dermal extension of fat cells, dermal atrophy, and loss of dermal collagen. A diagnosis of almost unilateral focal dermal hypoplasia was made on the basis of physical and histologic findings. Henceforth, the patient was referred to a plastic surgeon and an orthopedics department to repair her syndactyly.

Almost Unilateral Focal Dermal Hypoplasia

Focal dermal hypoplasia, caused by mutations in PORCN, is an X-linked ectodermal dysplasia, also known as Goltz syndrome. Only seven cases of unilateral or almost unilateral focal dermal hypoplasia have been reported in the English literature and there have been no previously reported cases in the Republic of Korea. A 19-year-old female presented with scalp defects, skin lesions on the right leg and the right trunk, and syndactyly of the right fourth and fifth toes. Cutaneous examination revealed multiple atrophic plaques and a brown and yellow mass with fat herniation and telangiectasia that was mostly located on the lower right leg. She had syndactyly on the right foot and the scalp lesion appeared to be an atrophic, membranous, fibrotic alopecic scar. A biopsy of the calf revealed upper dermal extension of fat cells, dermal atrophy, and loss of dermal collagen. A diagnosis of almost unilateral focal dermal hypoplasia was made on the basis of physical and histologic findings. Henceforth, the patient was referred to a plastic surgeon and an orthopedics department to repair her syndactyly.

Multiple apocrine hidrocystomas accompanied by apocrine hyperplasia:a case report / 中华皮肤科杂志

A 38-year-old man complained of multiple papules and nodules in the left retroauricular region for 38 years. On physical examination, there were tens of irregularly sized, skin-colored or pink papules and nodules in the left retroauricular region. Pathological examination showed a large irregularly shaped unilocular cystic space surrounded by a fibrous pseudocapsule in the dermis. The cystic space was lined by a double layer of epithelial cells, including an outer layer of flattened vacuolated myoepithelial cells and an inner layer of cuboidal or columnar secretory cells with eosinophilic cytoplasm. Apocrine secretion was present. Numerous hyperplastic apocrine glands were seen in the deep dermis. A final diagnosis of multiple apocrine hidrocystomas accompanied by apocrine hyperplasia was rendered based on the clinical and pathological presentations.

Cutaneous mosaicisms: concepts, patterns and classifications / Mosaicismos cutaneos: conceitos, padroes e classificacoes

A mosaic is an organism composed of two or more genetically distinct cell populations derived from a genetically homogeneous zygote. Cutaneous mosaicisms are the clinical expressions of these disorders. The main event which allows the existence of mosaicism is a genetic mutation, either structural or functional. Cutaneous mosaicisms usually manifest by specific patterns on the skin and the archetypic pattern is the system of Blaschko lines, but others include checkerboard, phylloid, large patches without midline separation and lateralization. Since 1901, when Blaschko lines were first described, the study of mosasicism has helped to elucidate the behavior of numerous genetic diseases, generating therapeutic perspectives for these pathologies, including the promising gene therapy.

Um mosaico é um organismo formado por duas ou mais populações de células geneticamente distintas originadas a partir de um mesmo zigoto geneticamente homogêneo. Os mosaicismos são as expressões clínicas dessa desordem, e a mutação gênica seu evento determinante, que pode ser tanto estrutural quanto funcional. Os mosaicismos cutâneos costumam se expressar em padrões específicos, dentre os quais podem ser mencionados as prevalentes linhas de Blaschko, o padrão "checkerboard", o padrão filóide, o padrão em placa sem separação na linha média e o padrão de lateralização, que serão abordados neste artigo. Desde 1901, momento da primeira descrição das linhas de Blaschko, o estudo dos mosaicismos tem contribuído para a elucidação do comportamento de numerosas desordens genéticas, de forma a criar perspectivas terapêuticas para essas doenças, incluindo a promissora terapia gênica.

Você conhece esta síndrome? / Do you know this syndrome?

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.

Goltz Syndrome Associated with Omphalocele

Goltz syndrome is a rare congenital disorder characterized by ectodermal and mesodermal dysplasia with multisystem defects. It was first reported in 1962 by Goltz as a focal dermal hypoplasia. More than 200 cases of Goltz syndrome were reported in the world literature, and 5 cases have been reported in Korea since 1994. There were few descriptions in the literature regarding surgical experience in Goltz syndrome. We report a female neonate born with omphalocele associated with Goltz syndrome that included typical cutaneous manifestations and a lobster-claw defect of the left foot. Omphalocele was successfully closed by staged reduction without any wound problems.

Hipoplasia dérmica focal (Síndrome de Goltz): amplia variabilidad fenotípica / Focal Dermal Hypoplasia (Goltz's Syndrome): Wide Phenotypic Variability

La hipoplasia dérmica focal (MIM# 305600), también llamada hipoplasia mesoectodérmica, es una rara entidad genética con un mecanismo de herencia dominante ligado al cromosoma X. Principalmente compromete piel, sistema esquelético, ojos y cara, con diferentes grados de severidad. Se describe dos casos clásicos e ilustrativos de hipoplasia dérmica focal, observando la amplia heterogeneidad fenotípica que estos pacientes pueden presentar. Hasta el momento es el segundo reporte en la literatura indexada de Colombia. Se realiza una amplia y actualizada revisión de la literatura.

The focal dermal hypoplasia (MIM # 305600), also called mesoectodermica hypoplasia is a rare disease. It is thought to be an X-linked dominant disorder. Mainly undertakes skin, skeletal system, eyes and face, with varying degrees of severity. We describe two cases illustrative of classical and focal dermal hypoplasia, noting the extensive phenotypic heterogeneity that these patients may present. So far is the second report in the literature indexed in Colombia, is a comprehensive and updated review of the literature.

Hipoplasia focal ectodérmica o síndrome de Goltz: manejo ortopédico témporomandibular / Focal dermal hypoplasia or Goltz síndrome: temporomandibular orthopedic management

El desarrollo embrionario es un conjunto de procesos que dan origen al organismo y en particular al macizo craneofacial. Se pueden producir múltiples alteraciones del desarrollo, dentro de las cuales está el Síndrome de Goltz. Se realiza el estudio de una paciente de sexo femenino de 21 años de edad, portadora de este síndrome, la que presenta alteraciones cutáneas, óseas y musculares. Estas se manifiestan principalmente por la falta de desarrollo del macizo craneofacial en el lado izquierdo (gran asimetría facial). A nivel dental se observa microdoncia, hipoplasia del esmalte, y una gingivitis generalizada. Asociado a este síndrome la paciente presentaba un trastorno temporomandibular severo, dolor de cabeza, dolor de oídos, mareos, sordera en el oído izquierdo y mala calidad de sueño. Es tratada durante seis meses con un plano oclusal con mayor altura de trabajo en el lado izquierdo, para estimular el trabajo muscular y descomprimir los tejidos de la ATM. Posteriormente se realiza un tratamiento de rehabilitación dental integral para lograr una estabilidad oclusal y mantener la posición mandibular. Con el tratamiento se logra un desarrollo músculo esqueletal del lado izquierdo, compensando la asimetría facial, mejoran los síntomas asociados a la patología témporomandibular, como el dolor de cabeza, la sordera izquierda y el funcionamiento articular. Podemos concluir que el Síndrome de Goltz afecta estructuras corporales y craneofaciales, provocando en esta paciente alteraciones cutáneas, esqueletales y un trastorno témporomandibular severo. El tratamiento con un aparato ortopédico permitió equilibrar el trabajo muscular del sistema craneocervicomandibular, mejorando la patología témporomandibular y los síntomas asociados.

The origin of craniofacial structures is a complex embryonary process. There could be different growth alterations of it; one of them is Goltz Syndrome. We report a case of a female patient, 21 years old who present skin, bone and muscular alterations. This alteration is mainly in the left craniofacial structures, resulting in facial asymmetry. She also presented microdontia, enamel hypoplasia, and generalized gingivitis. A severe Temporomandibular disorder (TMD) was also associated with headaches, earaches, dizziness, deafness in the left ear and poor sleep quality. She was treated for 6 months with an occlusal splint, higher in the left side to stimulate the muscular activity and give some relief to the left TMJtissues. Subsequently, a complete oral rehabilitation treatment was performed to achieve occusal stability and to perpetuate the mandibular position. After the treatment, the patient presented more development in the left muscular and skeletal structures, improving the facial symmetry, and eliminating headaches, earaches, dizziness, deafness in the left ear and poorsleep quality.

A Case of Goltz Syndrome / 대한피부과학회지

Goltz syndrome or focal dermal hypoplasia, is a rare genodermatosis, characterized by multiple abnormalities of mesodemal and ectodermal organs. Cutaneous manifestations include linear or cribriform atrophied patches with telangiectasia following Blaschko line and papillomas. The majority of patients also have skeletal abnormalities, such as syndactyly, oligodactyly, scoliosis, and short stature. Furthermore, various ophthalmic and dental manifestations have been reported. We report a case of Goltz syndrome occurring in a 2-year old female with asymptomatic erythematous atrophic patches with purpuric macules and telangiectasia mainly on extremities. She also had hypotrichia on vertex and a notching-like cleft on upper lip. A skin biopsy performed on her atrophic patch on the leg revealed dermal hypoplasia. The final diagnosis was made by typical cutaneous manifestations and histopathological findings compatible with focal dermal hypoplasia.

A Case of Goltz Syndrome

Goltz syndrome(focal dermal hypoplasia) is a rare disorder characterized by ectodermal and mesodermal dysplasia described in 1962 by Goltz. In Korea, one case of Goltz syndrome was reported in 1994. The inheritance mode is mostly X-linked dominant. Skin abnormality is the most common manifestation including hypoplasia of the dermis. Skeletal involvement such as syndactyly, polydactyly, scoliosis, kyphosis and spina bifida occulta may be present, also ocular and dental abnormalities are reported. Radiologic findings are the osteopathy and striation of the long bone. We experienced a case of Goltz syndrome in a 9-year old female who was presented with right side hypotrophy, focal dermal hypoplasia, ocular(anidria, microcornea), dental(oligodontia, amelogenesis) and skeletal(syndactyly) abnormalities. Skin biopsy was performed and showed decreased expression of type I collagen gene with Northern blotting.

A Case of Focal Dermal Hypoplasia / 대한피부과학회지

Focal dermal hypoplasia or Goltz syndrome is a rare genetic mesodermal and ectodermal disorder characterized by variable multisystem defects, including anomalies of the skin, skeleton, teeth and eyes. The disorder appears to be lethal in males and there is a large dominance of female cases; hence, X-linked dominant inheritance has been postulated. A 10-year-old female patient presented with soft extruding nodules on the hyperpigmented patch on the right leg, reticulated hyperpigmentd patches and plaques scattered over the trunk and extremities, and focal alopecia on the scalp. In addion to the skin lesions, this patient showed syndactyly of the right 2nd, 3rd fingers and 4th, 5th fingers, developmental anomaly of the right foot including syndactyly and hypoplasia of the toes, hemiatrophy of the right side of the face, and irregular spacing of teeth and malocclusion. Histopathological findings of soft pinkish nodule on the right leg revealed very thin layered collagen fibers on the dermis and presence of adipose tissue very near to the epidermis that largely replaced the upper dermis.

Focal Dermal Hypoplasia Associated with Ichthyosis

We report a case of focal dermal hypoplasia associated with ichthyosis in an 18-year-old Korean female. The patient showed a yellowish atrophic patch on the left side of her abdomen, abnormal skin pigmentation, nail dystrophy and ichthyosis since birth.We could also find skeletal and dental deformities. The biopsy specimen obtained from the yellowish atrophic patch showed marked attenuation of collagen fibers and ectopic fatty tissue nearly reaching up to the upper dermis.

Focal Dermal Hypoplasia Associated with Ichthyosis

We report a case of focal dermal hypoplasia associated with ichthyosis in an 18-year-old Korean female. The patient showed a yellowish atrophic patch on the left side of her abdomen, abnormal skin pigmentation, nail dystrophy and ichthyosis since birth.We could also find skeletal and dental deformities. The biopsy specimen obtained from the yellowish atrophic patch showed marked attenuation of collagen fibers and ectopic fatty tissue nearly reaching up to the upper dermis.

A case of focal dermal hypoplasia / 대한피부과학회지

Focal dermal hypoplasia (Goltz syndrome) is a rare genetic mesoectodermal disorder characterized by variable multisystem defects, including anomalies of the skin, skeleton, teeth and eyes. A 22-year-old female patient presented with confluent and disciete, yellowish nodules on the calves, white linear atrophic lesions, hypoand hyper!igmented patches, and telangiectasia scattered over the trunk, neck and extremities. In addition to the skin lesions, this patient showed hypertrophy of the left leg, anomalies of the left foot, fingers and nails, and maloccluded teeth. Histopathological findings of a yellow nodule revealed accumulations of adipose tissue very near to the epidermis that largely replaced the upper dermis.