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2.
J Clin Ultrasound ; 51(1): 96-106, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36639848

RESUMO

PURPOSE: Antenatal detection of limb anomalies is not uncommon, and pregnancies are usually terminated in view of the expected physical handicap. The aim of this retrospective observational study is to delineate the spectrum of fetal limb anomalies and provide evidence in support of complete postnatal evaluation in establishing recurrence risk. METHODS: We present 54 cases of limb malformations detected antenatally and discuss the spectrum of abnormalities, the utility of fetal autopsy, and genetic testing to establish recurrence risk in subsequent pregnancies. RESULTS: 16/54 cases were isolated radial ray anomalies. There were five cases of amniotic band syndrome, five limb body wall complex cases, three VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) associations, one case of sirenomelia, two cases of limb pelvis hypoplasia, and one case of OEIS (Omphalocele Exstrophy Imperforate anus and spinal defects). Four fetuses with non-isolated radial ray anomaly had trisomy 18. One case with bilateral radial ray defect had a mutation in the FANC-E gene confirming fanconi anemia. Twelve cases were unclassified. CONCLUSION: Autopsy is the most important investigation in fetuses with limb anomalies. We suggest chromosomal microarray (CMA) as a first-tier test after autopsy. However, in cases of bilaterally symmetrical limb anomalies, in case of previous similarly affected child, or history of consanguinity, whole exome sequencing (WES) can be offered as the primary investigation, followed by CMA if WES is normal.


Assuntos
Cardiopatias Congênitas , Deformidades Congênitas dos Membros , Fístula Traqueoesofágica , Feminino , Humanos , Gravidez , Feto/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/genética , Rim/anormalidades , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Traqueia/anormalidades , Fístula Traqueoesofágica/diagnóstico por imagem , Fístula Traqueoesofágica/genética , Diagnóstico Pré-Natal
3.
Neuroreport ; 34(1): 56-60, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36504041

RESUMO

OBJECTIVES: Delay-discounting, wherein the subjective value for delayed gain or loss decreases, has been attracting much attention from the social sciences as well as neuroscience and has been suggested asbeing related to reward processing in the brain. As reported, the feedback-related negativity (FRN), an electrophysiological measure of reward processing, increased by delayed-monetary gain and ΔFRN, which is the difference in FRNs for loss and gain at a certain time point, had no significant correlation with delay-discounting for gain. Thus, although a delay for gain could affect FRN, it is unclear whether FRN capturing such a delay effect has a direct relationship with delay-discounting in both gain and loss domains. METHODS: In this study, we introduced a delay-specific indicator, ΔFRNdelay, that is, the difference between FRN with and without delays, and investigated its direct relationship during the doors task with the discounting rate measured by the delay-discounting task in both the gain and loss domains. RESULTS: We found that, for loss, the delay enhanced FRN, whereas no such effect was observed for gains, and that this indicator was significantly correlated with delay-discounting in both domains. CONCLUSIONS: To our knowledge, this study is the first to suggest that FRN is sensitive to the effects of delay in losses on reward processing and that the new indicator directly corresponds to changes in subjective value as measured by delay-discounting.


Assuntos
Hérnia Diafragmática , Deformidades Congênitas dos Membros , Humanos , Encéfalo , Recompensa , Facies
4.
Arch. pediatr. Urug ; 93(2): e317, dic. 2022. ilus, graf
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1411577

RESUMO

La hipocondroplasia es una displasia esquelética caracterizada por baja estatura, constitución robusta, brazos y piernas desproporcionadamente cortos, manos y pies anchos y cortos, leve laxitud articular y macrocefalia. Los niños generalmente se presentan como pequeños, con velocidad de crecimiento disminuida, que conduce a una baja estatura y desproporción de las extremidades. La hipocondroplasia en la mayoría de los casos se hereda con carácter autosómico dominante, aunque se detectan numerosos casos esporádicos. El diagnóstico requiere una exhaustiva anamnesis y adecuada exploración física. Es importante valorar algunos indicadores de crecimiento como: peso para la edad, longitud/talla para la edad, relación entre peso y longitud/talla, velocidad de crecimiento, talla diana genética, medidas de segmentos corporales, entre otros. Las radiografías esqueléticas permiten diagnosticar la mayoría de las displasias óseas. Los estudios moleculares suelen ser la prueba de confirmación y se solicitan ante una sospecha diagnóstica. Es importante incluir las displasias óseas en el diagnóstico diferencial de la talla baja y tenerlas en cuenta ante cualquier caso de talla baja disarmónica con alteraciones fenotípicas. La hipocondroplasia en la actualidad, no es una indicación aprobada para tratamiento con hormona del crecimiento. Se presenta un caso clínico de una niña de 14 meses, con talla baja severa, desproporcionada, que presentó dificultades para llegar al diagnóstico definitivo de hipocondroplasia.


Hypochondroplasia is a skeletal dysplasia characterized by short height, robust build, disproportionately short arms and legs, short and broad hands and feet, mild joint laxity, and macrocephaly. Children generally show slow growth rate, which leads to short stature and limb disproportion. Hypochondroplasia is mostly inherited with an autosomal dominant character, although many sporadic cases have been detected. Diagnosis requires a thorough history and adequate physical examination. It is important to assess some growth indicators such as: weight for age, length/height for age, relationship between weight and length/height, growth speed, genetic target height, measurements of body segments, among others. Skeletal XRs can diagnose most bone dysplasias. Molecular studies are usually the confirmatory test and are requested when a diagnosis is suspected. It is important to include bone dysplasias in the differential diagnosis of short stature and to take them into account for any disharmonious short stature with phenotypic alterations. Hypochondroplasia is currently not an approved indication for growth hormone therapy. We present a clinical case of a 14-month-old girl, with a severe, disproportionate short stature, who presented difficulties in her definitive hypochondroplasia diagnosis.


A hipocondroplasia é uma displasia esquelética caracterizada por baixa estatura, constituição robusta, braços e pernas desproporcionalmente curtos, mãos e pés largos e curtos, frouxidão articular leve e macrocefalia. As crianças geralmente são pequenas, com diminuição da velocidade de crescimento, o que leva à baixa estatura e desproporção dos membros. A hipocondroplasia na maioria dos casos é herdada com caráter autossômico dominante, embora sejam detectados numerosos casos esporádicos. O diagnóstico requer uma história completa e um exame físico adequado. É importante avaliar alguns indicadores de crescimento como: peso para idade, comprimento/altura para idade, relação entre peso e comprimento/altura, taxa de crescimento, estatura alvo genético, medidas de segmentos corporais, entre outros. As radiografias esqueléticas permitem o diagnóstico da maioria das displasias ósseas. Os estudos moleculares são geralmente o teste de confirmação e são solicitados quando há suspeita de diagnóstico. É importante incluir as displasias ósseas no diagnóstico diferencial da baixa estatura e considerá-las em qualquer caso de baixa estatura desarmônica com alterações fenotípicas. A hipocondroplasia não é atualmente uma indicação aprovada para o tratamento com hormônio de crescimento. Apresenta-se o caso clínico de uma menina de 14 meses, com baixa estatura grave e desproporcional, que apresentou dificuldades em chegar ao diagnóstico definitivo de hipocondroplasia.


Assuntos
Humanos , Feminino , Lactente , Osso e Ossos/anormalidades , Deformidades Congênitas dos Membros/diagnóstico , Nanismo/diagnóstico , Lordose/diagnóstico
5.
J Craniofac Surg ; 33(8): e831-e834, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36409858

RESUMO

Orofaciodigital syndrome type 1 (OFDS1) is a genetic disorder characterized by specific oral, facial, and limb malformations. A 14-month-old girl with congenital cleft palate, lower lip midline cleft, and digital anomalies admitted to our hospital was preliminarily diagnosed with OFDS1. Genetic analysis revealed that she carried a heterozygous variant of OFD1 at locus Xp22.2 on the X chromosome. Herein, we present the specific phenotype and genotype and the treatment modalities for this patient and references for diagnosing and treating OFDS.


Assuntos
Fissura Palatina , Deformidades Congênitas dos Membros , Síndromes Orofaciodigitais , Feminino , Humanos , Síndromes Orofaciodigitais/diagnóstico , Síndromes Orofaciodigitais/genética , Éxons , Face , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Fissura Palatina/cirurgia
6.
Birth Defects Res ; 114(20): 1427-1433, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36353751

RESUMO

BACKGROUND: Amelia and phocomelia represent severe limb reduction defects. Specific epidemiologic data on these defects are scarce. We conducted a descriptive analysis of prevalence data in Finland during 1993-2008 to clarify the epidemiology nationwide in a population-based register study. We hypothesized that increasing maternal age would affect the total prevalence of each disorder. MATERIALS AND METHODS: We collected information on all fetuses and infants affected by amelia and phocomelia during 1993-2008 from the National Register of Congenital Malformations in Finland. The clinical, laboratory, autopsy, and imaging data were re-evaluated where available for all cases found. RESULTS: A total of 23 amelia and 7 phocomelia patients were identified. Thalidomide was not an etiological factor in any of the cases. The total prevalence of amelia was 2.43 per 100,000 births. The live birth prevalence was 0.63 per 100,000 live births. The total prevalence of phocomelia was 0.74 per 100,000 births, and the live birth prevalence was 0.53 per 100,000 live births. Infant mortality in amelia and phocomelia was 67% and 60%, respectively. CONCLUSIONS: Infant mortality is high among amelia and phocomelia. Most cases had other major associated anomalies, but syndromic amelia cases were rare. Total prevalences were higher than previously reported and showed an increase in prevalence toward the end of the study period. The percentage of elective terminations of pregnancy for these disorders is high. While isolated cases are rare, they most likely present a better prognosis. Thus, correct diagnosis is essential in counseling for possible elective termination.


Assuntos
Ectromelia , Deformidades Congênitas dos Membros , Gravidez , Lactente , Feminino , Humanos , Ectromelia/epidemiologia , Prevalência , Finlândia/epidemiologia , Idade Materna
7.
Eur J Med Genet ; 65(12): 104653, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36330903

RESUMO

Adams-Oliver syndrome (AOS) is diagnosed in presence of aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). The autosomal recessive (AR) DOCK6-related form of AOS is most often associated with a severe phenotype including also central nervous system and ocular abnormalities. We report a sister and brother with different expression of the phenotype. Both were compound heterozygous pathogenic variants in the DOCK6 gene, including a heterozygous c.5939+2T > C intronic variant that was maternally inherited, and a heterozygous deletion of exons 10 to 21 that was paternally inherited. The sister had microcephaly, periventricular calcifications, minor retinal vasculopathy, and mild impaired neurodevelopment, but only very subtle limb abnormalities and no ACC. Her brother showed a classical DOCK6-related AOS phenotype, including a severe bilateral peripheral ischemic retinopathy. From a review of 22 molecularly confirmed cases with DOCK6-related AOS with ophthalmic examination, we found that 16 of them had retinal vascular pathology (72.7%), confirming as the major ocular anomaly. Documented intrafamilial variability in our family and the evidence revised from previous reports, confirm that AR DOCK6-related AOS expressivity can produce a "milder" phenotype without ACC or TTLD, which could be underdiagnosed in simplex cases because it is difficult to recognize out of a familial context. Therefore, in order to know its real magnitude is required the future inclusion of DOCK6 gene in NGS panels directed to the study of simplex cases of patients with microcephaly, periventricular calcifications, retinal vasculopathy, and/or cardiovascular defects.


Assuntos
Displasia Ectodérmica , Deformidades Congênitas dos Membros , Microcefalia , Feminino , Humanos , Masculino , Variação Biológica da População , Displasia Ectodérmica/genética , Displasia Ectodérmica/diagnóstico , Fatores de Troca do Nucleotídeo Guanina/genética , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/diagnóstico , Microcefalia/genética , Couro Cabeludo
8.
Genes (Basel) ; 13(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36421794

RESUMO

We report on a cohort of 204 children referred between January 2017 and January 2022 to the German Center for Ectodermal Dysplasias, Erlangen. The most frequent reasons for referral were tooth malformations and lack of multiple teeth leading to the suspicion of an ectodermal dysplasia. Many patients also suffered from being unable to perspire. Nail abnormalities, in contrast, represented a much rarer finding, albeit the impact on some individuals was large. As ectodermal dysplasias are congenital genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands, we analyzed congenital nail disorders detected in these patients. Dystrophic or otherwise abnormal nails were evident in 17 of 18 subjects with pathogenic WNT10A or GJB6 variants but in none of 161 children with EDA variants underlying X-linked hypohidrotic ectodermal dysplasia. However, 2 of 17 children who carry mutations in EDAR or EDARADD, two other genes involved in the ectodysplasin A signaling pathway, showed nail abnormalities, such as brittle or hypoplastic nails. TP63 variants were regularly associated with nail disorders. In one girl, anonychia congenita caused by a compound heterozygous variant of the R-spondin-4 gene (RSPO4) was diagnosed. Thus, nail dysplasia is rarer among patients with ectodermal dysplasia than commonly thought.


Assuntos
Displasia Ectodérmica , Deformidades Congênitas dos Membros , Unhas Malformadas , Criança , Feminino , Humanos , Unhas , Displasia Ectodérmica/genética , Unhas Malformadas/genética , Ectoderma
9.
Medicina (Kaunas) ; 58(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36363484

RESUMO

Background and Objectives: Pathogenic variants of PIGN are a known cause of multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Many affected individuals have clinical features overlapping with Fryns syndrome and are mainly characterised by developmental delay, congenital anomalies, hypotonia, seizures, and specific minor facial anomalies. This study investigates the clinical and molecular data of three individuals from two unrelated families, the clinical features of which were consistent with a diagnosis of MCAHS1. Materials and Methods: Next-generation sequencing (NGS) technology was used to identify the changes in the DNA sequence. Sanger sequencing of gDNA of probands and their parents was used for validation and segregation analysis. Bioinformatics tools were used to investigate the consequences of pathogenic or likely pathogenic PIGN variants at the protein sequence and structure level. Results: The analysis of NGS data and segregation analysis revealed a compound heterozygous NM_176787.5:c.[1942G>T];[1247_1251del] PIGN genotype in family 1 and NG_033144.1(NM_176787.5):c.[932T>G];[1674+1G>C] PIGN genotype in family 2. In silico, c.1942G>T (p.(Glu648Ter)), c.1247_1251del (p.(Glu416GlyfsTer22)), and c.1674+1G>C (p.(Glu525AspfsTer68)) variants are predicted to result in a premature termination codon that leads to truncated and functionally disrupted protein causing the phenotype of MCAHS1 in the affected individuals. Conclusions: PIGN-related disease represents a wide spectrum of phenotypic features, making clinical diagnosis inaccurate and complicated. The genetic testing of every individual with this phenotype provides new insights into the origin and development of the disease.


Assuntos
Deformidades Congênitas dos Membros , Hipotonia Muscular , Humanos , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Lituânia , Fosfotransferases/genética , Convulsões , Síndrome , Mutação , Linhagem
10.
Med Arch ; 76(4): 301-304, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36313953

RESUMO

Background: Focal dermal hypoplasia is a genetic disease of multiple systems initially affecting the skin, skeleton, dental, eyes and face with developmental abnormalities and facial dysmorphism. Focal dermal hypoplasia is X-linked dominant disease affecting the ectoderm, mesoderm and endoderm. 95% feature de novo and 90% of these are females. Focal dermal hypoplasia is induced by a mutation in the PORCN gene. Objective: The aim of this article is to present a case of a one-year-old girl child with multi-hypopigmented reticulated atrophic macules and patches grouped in linear mode at the lines of blaschko, skeleton abnormalities, umbilical hernia, developmental delay, hypoplastic nails, syndactyly and lobster claw deformity. Case report: A one-year-old girl child presented to the dermatology clinic with asymptomatic lesions since childhood with no improvement, with multi- hypopigmented skin lesions on the trunk and extremities since birth as linear erosions that heal gradually during few days, leaving peripheral hypopigmentation with hyperpigmentation with anomalies of limbs and nails and delayed development. She was born by normal vaginal delivery and weighed 2.5 kg at birth. None of the family members had such features. She had dental enamel anomaly and partial anodontia in the lower jaw. Sparse hair and partial alopecia (scalp, eyebrows and eyelashes) were recorded. Conclusion: Focal dermal hypoplasia is a congenital skin disease with a unique clinical feature. Thorough examination of the extremities is indicated for early proper genetic counseling and therapy.


Assuntos
Hipoplasia Dérmica Focal , Deformidades Congênitas dos Membros , Feminino , Humanos , Lactente , Aciltransferases/genética , Hipoplasia Dérmica Focal/diagnóstico , Hipoplasia Dérmica Focal/genética , Hipoplasia Dérmica Focal/patologia , Deformidades Congênitas dos Membros/patologia , Proteínas de Membrana/genética , Mutação , Pele/patologia
11.
Pol Merkur Lekarski ; 50(299): 302-305, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36283013

RESUMO

Robinow syndrome is a rare congenital syndrome described in 1969 by Meinhard Robinow. The genetic background is heterogeneous - mutations of DVLI1, DVLI3, WNT5A genes (mild, autosomal dominant inheritance) or ROR2 gene (severe, autosomal recessive inheritance) are responsible for the syndrome. The syndrome is characterized by facial dysmorphism, skeletal defects, short stature, cardiovascular and urinary system abnormalities. CASE REPORT: We report nephrological and urological problems in two 4-year-old male patients with Robinow syndrome. The first patient has a horseshoe kidney located mainly on the right side, right vesicoureteral reflux grade II, dysfunctional voiding, buried penis, and retractile testicles. The second patient has recurrent urinary tract infections; diagnostic findings include left kidney duplication, grade II left vesicoureteral reflux, large posterior urethral diverticulum, dysfunctional voiding, buried penis, glanular hypospadias, and bilateral cryptorchidism. CONCLUSIONS: Patients with Robinow syndrome require multidisciplinary care, including nephrology-urology care. Nephrological and urological manifestations in children with Robinow syndrome are diverse, and urinary tract defects may be atypical and complex.


Assuntos
Nanismo , Deformidades Congênitas dos Membros , Nefrologia , Refluxo Vesicoureteral , Criança , Masculino , Humanos , Adulto Jovem , Adulto , Refluxo Vesicoureteral/complicações , Refluxo Vesicoureteral/diagnóstico , Deformidades Congênitas dos Membros/genética , Nanismo/genética , Síndrome
12.
Artigo em Inglês | MEDLINE | ID: mdl-36307211

RESUMO

We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G > C (p.Cys3807Ser) and c.12407T > G (p.Val4136Gly) in LRP1, in which segregation analysis helped dismiss additional variants of interest. LRP1 analysis using multiple human/mouse data sets reveals a correlation to patient phenotypes of Peters plus syndrome with additional severe cardiomyopathy and blood vessel development complications linked to neural crest cells.


Assuntos
Fenda Labial , Permeabilidade do Canal Arterial , Cardiopatias Congênitas , Deformidades Congênitas dos Membros , Animais , Humanos , Camundongos , Fenda Labial/complicações , Doenças da Córnea/metabolismo , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/genética , Deformidades Congênitas dos Membros/complicações , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Síndrome , Doenças Ósseas/complicações , Doenças Ósseas/genética , Doenças Ósseas/metabolismo , Pneumopatias/complicações , Pneumopatias/genética , Pneumopatias/metabolismo
13.
J Plast Reconstr Aesthet Surg ; 75(11): 4054-4062, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36175329

RESUMO

BACKGROUND: Macrodactyly is a very rare congenital difference that affects hands and feet with significant developmental and psychological implications. Macrodactyly is attributed to a somatic mutation in PIK3CA, a component of the mTOR pathway-related overgrowth disorders. Other medical conditions have been associated with macrodactyly (e.g., neurofibromatosis and Proteus syndrome). A thorough investigation of the presence of these conditions should be undertaken by the multidisciplinary team. The aim of this study is to summarize the main clinical characteristics and associated conditions, with an emphasis on diagnosis and surgical treatment options. MATERIALS AND METHODS: We present several clinical cases after a retrospective chart review of macrodactyly cases and a comprehensive literature review. RESULTS: The indications for surgery include peripheral compressive neuropathies (e.g., carpal tunnel syndrome), grotesque enlargement interfering with function, psychosocial distress due to the deformity, and macrodystrophic lipomatosis with proximal upper limb involvement. The main surgical treatment options are categorized as follows: digit reduction (e.g., soft tissue debulking, skeletal shortening/ terminalization, Barsky procedure, and Tsuge technique), limitation of growth (digital nerve stripping and epiphysiodesis), and correction of deviation (wedge or angulation osteotomy, arthrodesis, Millesi procedure for thumb macrodactyly correction, toe-to-hand transfer, ray resection, and combination of bony reduction and soft tissue debulking). CONCLUSIONS: Macrodactyly correction requires surgical experience and an individualized approach. Treatment is primarily surgical; however, efforts are being made to delineate the root cause of macrodactyly and provide nonoperative management.


Assuntos
Dedos , Deformidades Congênitas dos Membros , Criança , Humanos , Estudos Retrospectivos , Dedos/cirurgia , Dedos/anormalidades , Deformidades Congênitas dos Membros/genética , Polegar/anormalidades
14.
Am J Med Genet A ; 188(11): 3318-3323, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36059114

RESUMO

Aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD) are the characteristic findings of Adams-Oliver syndrome (AOS). The variable clinical spectrum further includes cardiac, neurologic, renal, and ophthalmological findings. Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT. The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl from a refugee family of Iraq with consanguineous parents. She was born with a severe phenotype of AOS presenting a large ACC of the scalp with an underlying skull defect, which was often infected and inflamed. Afterward, additional ulceration developed. Furthermore, the girl showed microcephaly, TTLD on both hands and feet, and neurological findings: spastic paresis, epilepsy and suspicion of intellectual deficit. Molecular genetic analysis (next-generation sequencing) revealed a novel frameshift mutation in the EOGT gene in Exon 13 in homozygous constellation: c.1013dupA p.(Asn338Lysfs*24). A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. Treatment including surgical resection and focal irradiation was not curative and the girl deceased 6 months after initial diagnosis. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.


Assuntos
Carcinoma de Células Escamosas , Displasia Ectodérmica , Deformidades Congênitas dos Membros , Dermatoses do Couro Cabeludo , Neoplasias Cutâneas , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Feminino , Mutação da Fase de Leitura , Humanos , Deformidades Congênitas dos Membros/genética , Mutação , N-Acetilglucosaminiltransferases/genética , Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/congênito , Dermatoses do Couro Cabeludo/diagnóstico , Dermatoses do Couro Cabeludo/genética , Dermatoses do Couro Cabeludo/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Crânio/patologia
16.
Int J Mol Sci ; 23(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36077575

RESUMO

Metabolic syndrome (MetS) is an extremely prevalent complex trait and it can originate in early life. This concept is now being termed the developmental origins of health and disease (DOHaD). Increasing evidence supports that disturbance of gut microbiota influences various risk factors of MetS. The DOHaD theory provides an innovative strategy to prevent MetS through early intervention (i.e., reprogramming). In this review, we summarize the existing literature that supports how environmental cues induced MetS of developmental origins and the interplay between gut microbiota and other fundamental underlying mechanisms. We also present an overview of experimental animal models addressing implementation of gut microbiota-targeted reprogramming interventions to avert the programming of MetS. Even with growing evidence from animal studies supporting the uses of gut microbiota-targeted therapies start before birth to protect against MetS of developmental origins, their effects on pregnant women are still unknown and these results require further clinical translation.


Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Probióticos , Anormalidades Múltiplas , Animais , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Eritrodermia Ictiosiforme Congênita , Deformidades Congênitas dos Membros , Síndrome Metabólica/tratamento farmacológico , Prebióticos , Gravidez , Probióticos/uso terapêutico
17.
Int J Legal Med ; 136(6): 1621-1636, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36180601

RESUMO

The present study combined three-dimensional (3D) motion capture with finite element simulation to reconstruct a real shaking adult syndrome (SAS) case and further explore the injury biomechanics of SAS. The frequency at which an adult male can shake the head of another person, head-shaking amplitude, and displacement curves was captured by the VICON 3D motion capture system. The captured shaking frequency and shaking curve were loaded on the total human model for safety (THUMS) head to simulate the biomechanical response of brain injury when a head was shaken in anterior-posterior, left-right, and left anterior-right posterior directions at frequencies of 4 Hz (Hz), 5 Hz, 6 Hz, and 7 Hz. The biomechanical response of the head on impact in the anterior, posterior, left, left anterior, and right posterior directions at the equivalent velocity of 6 Hz shaking was simulated. The violent shaking frequency of the adult male was 3.2-6.8 Hz; head shaking at these frequencies could result in serious cerebral injuries. SAS-related injuries have obvious directionality, and sagittal shaking can easily cause brain injuries. There was no significant difference between the brain injuries caused by shaking in the simulated frequency range (4-7 Hz). Impact and shaking at an equivalent velocity could cause brain injuries, though SAS more commonly occurred due to the cumulative deformation of brain tissue. Biomechanical studies of SAS should play a positive role in improving the accuracy of forensic identification and reducing this form of abuse and torture in detention or places of imprisonment.


Assuntos
Lesões Encefálicas Traumáticas , Síndrome do Bebê Sacudido , Adulto , Anodontia , Fenômenos Biomecânicos , Mama/anormalidades , Hemorragia Cerebral , Displasia Ectodérmica , Análise de Elementos Finitos , Humanos , Obstrução dos Ductos Lacrimais , Deformidades Congênitas dos Membros , Masculino , Modelos Biológicos , Unhas Malformadas , Transtornos da Pigmentação , Síndrome do Bebê Sacudido/etiologia
18.
PLoS Genet ; 18(8): e1010335, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35951645

RESUMO

Notch signaling is a conserved pathway that converts extracellular receptor-ligand interactions into changes in gene expression via a single transcription factor (CBF1/RBPJ in mammals; Su(H) in Drosophila). In humans, RBPJ variants have been linked to Adams-Oliver syndrome (AOS), a rare autosomal dominant disorder characterized by scalp, cranium, and limb defects. Here, we found that a previously described Drosophila Su(H) allele encodes a missense mutation that alters an analogous residue found in an AOS-associated RBPJ variant. Importantly, genetic studies support a model that heterozygous Drosophila with the AOS-like Su(H) allele behave in an opposing manner to heterozygous flies with a Su(H) null allele, due to a dominant activity of sequestering either the Notch co-activator or the antagonistic Hairless co-repressor. Consistent with this model, AOS-like Su(H) and Rbpj variants have decreased DNA binding activity compared to wild type proteins, but these variants do not significantly alter protein binding to the Notch co-activator or the fly and mammalian co-repressors, respectively. Taken together, these data suggest a cofactor sequestration mechanism underlies AOS phenotypes associated with RBPJ variants, whereby the AOS-associated RBPJ allele encodes a protein with compromised DNA binding activity that retains cofactor binding, resulting in Notch target gene dysregulation.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Proteínas Correpressoras , DNA , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Displasia Ectodérmica , Humanos , Deformidades Congênitas dos Membros , Mamíferos/genética , Receptores Notch/genética , Receptores Notch/metabolismo , Couro Cabeludo/metabolismo , Dermatoses do Couro Cabeludo/congênito , Crânio/metabolismo
19.
J Pediatr Endocrinol Metab ; 35(11): 1443-1447, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-35942587

RESUMO

OBJECTIVES: Short stature is one of the most common reasons for consulting a paediatric endocrinologist. Targeted diagnosis of familial short stature can be challenging due to a broad spectrum of differential diagnoses. CASE PRESENTATION: Here we report a novel mutation in the fibrillin 1 gene (FBN1) in six family members causing a mild phenotype of acromicric dysplasia. Additionally, we present the effects of growth hormone therapy in one of the affected children. CONCLUSIONS: Acromicric dysplasia is a very rare skeletal dysplasia with a prevalence of <1 of 1.000.000 with only about 60 cases being reported worldwide. It is characterized by short stature, acromelia, mild facial dysmorphy but normal intelligence. This study aims to exemplify the clinical and molecular features of FBN1-related acromicric dysplasia and illustrates its pleiotropy by presenting a new, mild phenotype.


Assuntos
Doenças do Desenvolvimento Ósseo , Nanismo , Deformidades Congênitas dos Membros , Humanos , Fibrilina-1/genética , Mutação de Sentido Incorreto , Doenças do Desenvolvimento Ósseo/genética , Deformidades Congênitas dos Membros/genética , Mutação
20.
J Morphol ; 283(9): 1257-1272, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35915891

RESUMO

Alvarezsauroidea (Tetanurae) are nonavian theropod dinosaurs whose forelimb evolution is characterised by the overdevelopment of digit I, at the expense of the other two digits, complemented by a drastic forelimb shortening in derived species (Parvicursorinae). These variations are recognised as evolutionary developmental anomalies. Evolutionary teratology hence leads to a double diagnosis with (1) macrodactyly of digit I and microdactyly of digits II and III, plus (2) anterior micromelia. The teratological macrodactyly/microdactyly coupling evolved first. Developmental mechanisms disturbing limb proportion are thought to be convergent with those of other Tetanurae (Tyrannosauridae, Carcharodontosauridae). As for the manual anomalies, both are specific to Alvarezsauroidea (macrodactyly/microdactyly) and inherited (digit loss/reduction). While considering the frame-shift theory, posterior digits develop before the most anterior ones. There would therefore be a decrease in the area devoted to digits II (condensation 3) and III (condensation 4), in connection with the Shh signalling pathway, interacting with other molecular players such as the GLI3 protein and the Hox system. Developmental independence of digit I (condensation 2) would contribute to generating a particular morphology. Macrodactyly would be linked to a variation in Hoxd-13, impacting Gli3 activity, and increasing cell proliferation. The loss/reduction of digital ray/phalanges (digits II and III), would be associated with Shh activity, a mechanism inherited from the theropodan ancestry. The macrodactyly/microdactyly coupling, and then anterior micromelia, fundamentally changed the forelimb mechanical function, compared to the 'classical' grasping structure of basal representatives and other theropods. The distal ossification of the macrodactylian digit has been identified as physiological, implying the use of the structure. However, the debate on a particular 'adaptive' use is pointless as the ecology of an organism is interactively complex, being both at the scale of the individual and dependent on circumstances. Other anatomical features also allow for compensation and different predation (cursorial hindlimbs).


Assuntos
Dinossauros , Teratologia , Animais , Dinossauros/anatomia & histologia , Dedos/anormalidades , Membro Anterior/anatomia & histologia , Membro Posterior , Deformidades Congênitas dos Membros
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