RESUMEN
Aortic aneurysms are rare in the pediatric age group and are commonly caused by genetic disorders associated with vasculopathy, weakness and fragility of arterial walls with progressive dilatation or even rupture. We reported a giant aortic aneurysm involving the ascending aorta and aortic arch in a 20-month-old girl with autosomal recessive cutis laxa type 1B (ARCL1B) who presented with hemorrhagic pericardial effusion and tamponade (impending rupture). Successful surgical repair has been done through excision of the aneurysmal part and replacement by Hemashield graft with preservation of the aortic valve.
Asunto(s)
Aneurisma de la Aorta Torácica , Aneurisma de la Aorta , Taponamiento Cardíaco , Cutis Laxo , Derrame Pericárdico , Taponamiento Cardíaco/diagnóstico , Taponamiento Cardíaco/diagnóstico por imagen , Niño , Cutis Laxo/diagnóstico , Cutis Laxo/diagnóstico por imagen , Femenino , Humanos , LactanteRESUMEN
AGel amyloidosis is a dominantly inherited systemic amyloidosis caused by mutations p.D214N or p.D214Y resulting in gelsolin amyloid (AGel) formation. AGel accumulates extracellularly in many tissues and alongside elastic fibres. AGel deposition associates with elastic fibre degradation leading to severe clinical manifestations, such as cutis laxa and angiopathic complications. We analysed elastic fibre pathology in dermal and vascular tissue and plasma samples from 35 patients with AGel amyloidosis and 40 control subjects by transmission electron microscopy, immunohistochemistry and ELISA methods. To clarify the pathomechanism(s) of AGel-related elastolysis, we studied the roles of MMP-2, -7, -9, -12 and -14, TIMP-1 and TGFß. We found massive accumulation of amyloid fibrils along elastic fibres as well as fragmentation and loss of elastic fibres in all dermal and vascular samples of AGel patients. Fibrils of distinct types formed fibrous matrix. The degradation pattern of elastic fibres in AGel patients was different from the age-related degradation in controls. The elastin of elastic fibres in AGel patients was strongly decreased compared to controls. MMP-9 was expressed at lower and TGFß at higher levels in AGel patients than in controls. The accumulation of amyloid fibrils with severe elastolysis characterises both dermal and vascular derangement in AGel amyloidosis.
Asunto(s)
Amiloidosis Familiar/fisiopatología , Cutis Laxo/fisiopatología , Gelsolina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Amiloide/metabolismo , Cutis Laxo/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
RIN2 syndrome also known as MACS syndrome is a rare autosomal recessive connective tissue disorder caused by RIN2 mutations and is accompanied by following clinical features: macrocephaly, coarsening of facial features, downward slanting palpebral fissures, Puffy droopy eyelids, full everted lips, soft redundant skin especially in face, gum hypertrophy, irregular dentition, sparse scalp hair, skeletal problems, joint hypermobility and scoliosis. RIN2 gene encodes the RAS and RAB interactor 2 and biallelic mutations in this gene cause cell trafficking dysfunction. Here we reported the eleventh patient of RIN2 syndrome in a 4 yr-old boy, from Tehran, Iran as the youngest reported patient so far. Whole exome sequencing revealed a novel frameshift homozygous variant of NM_001242581.1: c.2251dup; p.(Leu751Profs*9) in RIN2 gene. In addition to the previously reported symptoms for the RIN2 syndrome, white matter abnormalities in his brain MRI were noticed. Our findings expand the clinical spectrum of MACS syndrome due to mutation in RIN2 gene.
Asunto(s)
Alopecia/genética , Proteínas Portadoras/genética , Enfermedades del Tejido Conjuntivo/genética , Cutis Laxo/genética , Factores de Intercambio de Guanina Nucleótido/genética , Leucoencefalopatías/genética , Megalencefalia/genética , Escoliosis/genética , Adulto , Alopecia/complicaciones , Alopecia/diagnóstico por imagen , Alopecia/patología , Preescolar , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Enfermedades del Tejido Conjuntivo/patología , Cutis Laxo/complicaciones , Cutis Laxo/diagnóstico por imagen , Cutis Laxo/patología , Cara/diagnóstico por imagen , Cara/patología , Femenino , Mutación del Sistema de Lectura/genética , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Leucoencefalopatías/complicaciones , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/patología , Imagen por Resonancia Magnética , Masculino , Megalencefalia/complicaciones , Megalencefalia/diagnóstico por imagen , Megalencefalia/patología , Linaje , Escoliosis/complicaciones , Escoliosis/diagnóstico por imagen , Escoliosis/patología , Sustancia Blanca/anomalías , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
The autosomal dominant progeroid form of cutis laxa is a recently identified multiple congenital anomaly disorder characterized by thin, wrinkled skin, a progeroid appearance, intra-uterine growth retardation, postnatal growth restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia and contractures. De novo heterozygous mutations in ALDH18A1 have been described in this condition. We present neuroimaging abnormalities in three patients. One patient had intracranial arterial and venous tortuosity, widened ventricular and extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and increased T2 signal intensity in the cerebral white matter over time. The second patient had vascular tortuosity. The third patient had prominent ventricular and extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological mechanism for the development of intracranial vascular tortuosity and discuss the anatomical basis of wide perivascular spaces in relation to this syndrome. Although we do not know the clinical implications of these cerebral vascular anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of these patients.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cutis Laxo/diagnóstico por imagen , Cutis Laxo/patología , Aldehído Deshidrogenasa/genética , Cutis Laxo/genética , Femenino , Humanos , Lactante , Masculino , Mutación , Neuroimagen/métodos , SíndromeRESUMEN
Cutis laxa syndromes are rare inherited disorders of skin and connective tissue metabolism associated with variable systemic involvement. The main clinical manifestation is loose, wrinkled, redundant, inelastic skin, hypotonia, typical facies including short nose and down-slanting palpebral fissures, and varying degrees of developmental delay. The aim of this report is to describe two siblings diagnosed with a moderate form of ATP6V0A2-related cutis laxa with polymicrogyria (cobblestone-like brain dysgenesis). One of the patients has myoclonic epilepsy which may have contributed to his more severe clinical presentation. The literature on cutis laxa syndromes is reviewed.
Asunto(s)
Cutis Laxo/patología , Cutis Laxo/fisiopatología , Epilepsias Mioclónicas/patología , Epilepsias Mioclónicas/fisiopatología , Polimicrogiria/patología , Polimicrogiria/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Niño , Cutis Laxo/complicaciones , Cutis Laxo/diagnóstico por imagen , Epilepsias Mioclónicas/complicaciones , Epilepsias Mioclónicas/diagnóstico por imagen , Femenino , Humanos , Masculino , Mutación , Polimicrogiria/complicaciones , Polimicrogiria/diagnóstico por imagen , HermanosRESUMEN
Cutis laxa (CL) or elastolysis is a rare inherited or acquired connective tissue disorder in which the skin becomes inelastic and hangs loosely in folds (Mitra et al., 2013). The clinical presentation and the type of inheritance show considerable heterogeneity (Shehzad et al., 2010). We aimed to present the atypical case of a young male patient diagnosed at 36-year-old with CL with systemic involvement. The complex medical history, with a suspected but unconfirmed progeria at nine months, repeated lung and urinary infections, complicated inguinoscrotal hernia, prostatic hypertrophy, bilateral entropion, colorectal diverticula and heart failure, suggested a systemic genetic disease, but the absence of family history made the diagnosis of CL difficult. The skin biopsy and the characteristic features discovered during anatomopathological exam made possible the positive and differential diagnosis, creating the link between the various organ involvement and CL diagnosis. Because of the age of our patient, of normal growth and mental development, and negative family history, we suspected an autosomal dominant form of CL with early onset and severe manifestation. Of course, we cannot exclude a recessive form, due to the heterogeneity of this disease.
Asunto(s)
Cutis Laxo/patología , Adulto , Bronquitis/diagnóstico por imagen , Bronquitis/patología , Niño , Colonoscopía , Cutis Laxo/diagnóstico por imagen , Epidermis/patología , Colágenos Fibrilares/metabolismo , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
We report on a 4-year-old girl with autosomal recessive cutis laxa, type IA, or pulmonary emphysema type (ARCL1A; OMIM #219100), with loose and wrinkled skin, mitral and tricuspid valve prolapse, conjunctivochalasis, obstructed nasolacrimal ducts, hypoplastic maxilla, and early childhood-onset pulmonary emphysema. Mutation analysis of FBLN5 showed a homozygous c.432C>G missense mutation, and heterozygosity in the parents. This is predicted to cause amino acid substitution p.Cys144Trp. Conjunctivochalasis or redundant folds of conjunctiva and obstructed nasolacrimal ducts have not been reported to be associated with FBLN5 mutations. Histopathological study of the conjunctival biopsy showed that most blood vessels had normal elastic fibers. The gingiva appeared normal, but histologically elastic fibers were defective. Scanning electron micrography of scalp hair demonstrated hypoplastic hair follicles. The cuticles appear intact underneath the filamentous meshwork.
Asunto(s)
Conjuntiva/anomalías , Cutis Laxo/complicaciones , Cutis Laxo/genética , Proteínas de la Matriz Extracelular/genética , Cabello/anomalías , Mutación/genética , Conducto Nasolagrimal/anomalías , Enfisema Pulmonar/complicaciones , Adulto , Preescolar , Conjuntiva/patología , Cutis Laxo/diagnóstico por imagen , Análisis Mutacional de ADN , Femenino , Cabello/patología , Cabello/ultraestructura , Humanos , Lactante , Recién Nacido , Conducto Nasolagrimal/patología , Enfisema Pulmonar/diagnóstico por imagen , Radiografía Torácica , Tomografía Computarizada por Rayos XAsunto(s)
Cutis Laxo/congénito , Cutis Laxo/complicaciones , Enfisema Pulmonar/complicaciones , Adolescente , Envejecimiento Prematuro/diagnóstico , Envejecimiento Prematuro/diagnóstico por imagen , Envejecimiento Prematuro/etiología , Cutis Laxo/diagnóstico , Cutis Laxo/diagnóstico por imagen , Femenino , Humanos , Enfisema Pulmonar/congénito , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/diagnóstico por imagen , Radiografía TorácicaRESUMEN
Ehlers-Danlos type IX syndrome, also called occipital horn syndrome (OHS), is a milder and rare form of Menkes disease where the patient reaches adulthood. As an X-linked disease, it typically occurs in male subjects, while female subjects are usually healthy carriers. OHS is mainly characterized by connective tissue disorders and slightly subnormal intelligence or signs of autonomic dysfunction are the only apparent neurological abnormalities, in connection with molecular defects in copper metabolism. Our purpose is to report on radiological skeletal findings that may be incidental or investigated when OHS is suspected and to underline the possible involvement and expression in the female. Moreover, the impact of skeletal findings is also highlighted in the prevention of serious complications of the disease.
Asunto(s)
Huesos/diagnóstico por imagen , Cutis Laxo/diagnóstico por imagen , Síndrome de Ehlers-Danlos/diagnóstico por imagen , Exostosis/diagnóstico por imagen , Hueso Occipital/diagnóstico por imagen , Cutis Laxo/diagnóstico , Cutis Laxo/genética , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Femenino , Genes Ligados a X , Humanos , Persona de Mediana Edad , RadiografíaRESUMEN
Congenital cutis laxa is a rare, clinically and genetically heterogeneous group of inherited disorders. It is characterized by degenerative changes in elastic fibres and manifests with skin laxity. Here we presented a six-month old boy with congenital cutis laxa associated with growth retardation. We reveal ultrastructural findings and discussed the differential diagnosis.
Asunto(s)
Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Cutis Laxo/diagnóstico por imagen , Trastornos del Crecimiento/diagnóstico por imagen , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Enfermedades del Tejido Conjuntivo/diagnóstico , Cutis Laxo/diagnóstico , Diagnóstico Diferencial , Trastornos del Crecimiento/diagnóstico , Humanos , Lactante , Masculino , UltrasonografíaRESUMEN
The arterial tortuosity syndrome is a rare congenital disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. Associated clinical features consist of excessively stretchable skin and joint laxity which is indicative of a connective tissue disorder such as Ehlers-Danlos or Cutis laxa syndrome. The gene locus of the arterial tortuosity syndrome has recently been localised on chromosome 20q13; inheritance ist autosomal recessive. - We report on a newborn with arterial tortuosity syndrome and hiatal hernia, bilateral hip dislocation, inguinal hernias and diffuse tortuosity of the great arteries including the aorta. Known gene loci involved in Ehlers-Danlos syndrome, cutis laxa syndrome and other connective tissue disorders were excluded by specific DNA markers. By homozygosity mapping with polymorphic microsatellite markers it was possible to confirm the gene locus for the ATS on chromosome 20q13. In addition to the presentation of this patient, a review of the literature is presented.
Asunto(s)
Enfermedades de la Aorta/genética , Anomalías Cardiovasculares/genética , Cutis Laxo/genética , Síndrome de Ehlers-Danlos/genética , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/genética , Enfermedades de la Aorta/diagnóstico por imagen , Anomalías Cardiovasculares/diagnóstico por imagen , Aberraciones Cromosómicas , Cromosomas Humanos Par 20 , Consanguinidad , Cutis Laxo/diagnóstico por imagen , Síndrome de Ehlers-Danlos/diagnóstico por imagen , Facies , Femenino , Genes Recesivos , Hernia Hiatal/diagnóstico por imagen , Hernia Hiatal/genética , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/genética , Humanos , Recién Nacido , Hipotonía Muscular/diagnóstico por imagen , Hipotonía Muscular/genética , RadiografíaRESUMEN
Four cases of acrogeria in one large family with multiple consanguineous marriages are reported. Inheritance is autosomal recessive. Evaluation of six generations of this family also showed six individuals with congenital blindness; this pedigree suggests autosomal recessive inheritance also for this disorder. Association of the two conditions was not seen in living members. The initial presentation in the patients with acrogeria was failure of growth during the first year of life, accompanied by characteristic facial appearance and cutaneous atrophy of the face and extremities. The radiologic features of these patients were acro-osteolysis, wide sutures and fontanelles, wormian bones, mandibular hypoplasia and avascular necrosis of the femoral heads. Other features were osteolysis of the clavicles, soft tissue calcification, osteoporosis and coxa valga, which have not been described in previous reported cases.
Asunto(s)
Anomalías Múltiples , Huesos/anomalías , Cutis Laxo/genética , Síndrome de Werner/genética , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/genética , Huesos/diagnóstico por imagen , Niño , Preescolar , Cutis Laxo/diagnóstico por imagen , Resultado Fatal , Femenino , Humanos , Lactante , Masculino , Linaje , Radiografía , Síndrome de Werner/diagnóstico por imagenRESUMEN
Two cases (mother and daughter) are reported of autosomal dominant cutis laxa which are unusual in being associated with early onset emphysema. Both mother and daughter have been smokers and are heterozygotes for the alpha 1 antitrypsin genotype. The combination of cigarette smoking and subnormal alpha 1 antitrypsin levels may explain the pulmonary spread in these two women who have what is usually a benign form of cutis laxa limited to the skin.
Asunto(s)
Cutis Laxo/genética , Enfisema Pulmonar/complicaciones , Adulto , Cutis Laxo/complicaciones , Cutis Laxo/congénito , Cutis Laxo/diagnóstico por imagen , Femenino , Genes Dominantes , Humanos , Pulmón/diagnóstico por imagen , Persona de Mediana Edad , RadiografíaRESUMEN
Two infants are described with congenital cutis laxa. They represent two distinct disorders. In the first, congenital cutis laxa is associated with a generalized disorder of elastic tissue in which there may be diaphragmatic or other hernias, diverticula of the gastrointestinal or urinary tract and infantile emphysema. The disease is fatal often within the first year. In the second, congenital cutis laxa is associated with widely patent anterior fontanel, a variety of malformations, and retarded growth and development. Recognition of these distinct syndromes in the newborn period and their recessive inheritance permit realistic discussion of the prognosis which is very different from the benign dominant forms of cutis laxa.