Asunto(s)
Cromosomas Humanos Par 10 , Mutación de Línea Germinal , Síndrome de Hamartoma Múltiple/genética , Fosfoproteínas Fosfatasas/genética , Monoéster Fosfórico Hidrolasas , Proteínas Tirosina Fosfatasas/genética , Proteínas Supresoras de Tumor , Animales , Secuencia de Bases , ADN , Genes Supresores de Tumor , Síndrome de Hamartoma Múltiple/enzimología , Humanos , Datos de Secuencia Molecular , Fosfohidrolasa PTENRESUMEN
Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by short stature, brachydactyly, joint stiffness, and characteristic eye anomalies including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described and a gene for AR WMS has recently been mapped to chromosome 19p13.3-p13.2. Here, we report on the exclusion of chromosome 19p13.3-p13.2 in a large AD WMS family and show that, despite clinical homogeneity, AD and AR WMS are genetically heterogeneous entities. Because two AD WMS families were consistent with linkage to chromosome 15q21.1, the fibrillin-1 gene was sequenced and a 24 nt in frame deletion within a latent transforming growth factor-beta1 binding protein (LTBP) motif of the fibrillin-1 gene was found in a AD WMS family (exon 41, 5074_5097del). This in frame deletion cosegregated with the disease and was not found in 186 controls. This study strongly suggests that AD WMS and Marfan syndrome are allelic conditions at the fibrillin-1 locus and adds to the remarkable clinical heterogeneity of type I fibrillinopathies.
Asunto(s)
Anomalías Múltiples/genética , Eliminación de Gen , Genes Dominantes/genética , Proteínas de Microfilamentos/genética , Sistemas de Lectura/genética , Adolescente , Adulto , Niño , Preescolar , Proteínas de la Matriz Extracelular/genética , Anomalías del Ojo/genética , Femenino , Fibrilina-1 , Fibrilinas , Trastornos del Crecimiento/genética , Humanos , Deformidades Congénitas de las Extremidades/genética , Masculino , Síndrome de Marfan/genética , Persona de Mediana Edad , Linaje , SíndromeRESUMEN
The nevoid basal-cell carcinoma syndrome is characterized by major manifestations, such as multiple basal-cell carcinomata, cysts of the jaws, and skeletal--specifically, rib--abnormalities. Findings in 53 patients and a review of the literature document both major and lesser-known manifestations of the disorder. The odontogenic keratocyst, which usually appears during adolescence, has a marked tendency to recur. In addition to the skin tumors, milia, epidermoid cysts, chalazia, comedones, and palmar and plantar pits are frequent. The skin tumors, originally thought to be independent of sun exposure, are more common in sun-exposed areas and are far less frequent and occur at a much later age in blacks than in whites. There is some evidence that radiation of the skin promotes the appearance of skin cancers in this disorder. Unilateral linear nevoid basal-cell carcinomas with comedones may represent postzygotic somatic mutation. A proclivity to other forms of neoplasia exists. Patients with this syndrome have had medulloblastoma, meningioma, ovarian fibroma, ovarian fibrosarcoma, fibrosarcoma of the jaws, cardiac fibroma, fetal rhabdomyoma, and lymphatic or chylous cysts of the mesentery. In addition to the usual modalities of treatment, topical immunotherapy and topical 5-fluorouracil have been used with success. Oral synthetic retinoids, such as 13-cis-retinoic acid, have been used to prevent new lesions from appearing and to arrest the growth of older lesions by inducing differentiation. The independent observations of increased prostaglandin levels associated both with odontogenic keratocyst expansion and aggression of basal cell cancers merit further investigation both as a fundamental cellular mechanism and as a possible basis for treatment (e.g., with antiprostaglandins). The key to pre- and early postnatal diagnosis of the disorder--as well as to an understanding of the basic abnormality--lies in molecular genetics. Prime attention should be given to finding the site of the gene through the use of DNA and other markers.
Asunto(s)
Síndrome del Nevo Basocelular/diagnóstico , Carcinoma Basocelular/diagnóstico , Adulto , Síndrome del Nevo Basocelular/patología , Síndrome del Nevo Basocelular/terapia , Huesos/anomalías , Enfermedades del Sistema Nervioso Central/diagnóstico , Diagnóstico Diferencial , Cara , Femenino , Neoplasias Cardíacas/diagnóstico , Humanos , Neoplasias Maxilomandibulares/diagnóstico , Masculino , Tumores Odontogénicos/diagnóstico , Neoplasias Cutáneas/diagnóstico , Terminología como Asunto , Neoplasias Urogenitales/diagnósticoRESUMEN
Ten cases of melanotic neuroectodermal tumor of infancy (MNTI) were studied. There were nine males and one female ranging in age from 2 weeks to 10 months; one patient was 8 years old. Sites of origin were the maxilla (five), epididymis (two), mandible (one), skull (one), and soft tissues of the cheek (one). Six tumors recurred from 1 to 18 months after diagnosis. One patient had widespread dissemination. Electron microscopic study of four cases showed cells with melanosomes at various stages of maturation, and cells with neuroblastic features, including neurosecretory granules and cytoplasmic processes. Nine cases of MNTI were studied immunohistochemically. Small neuroblastic cells and large cells in all cases were reactive for neuron-specific enolase (NSE), synaptophysin, HMB45, and dopamine-beta-hydroxylase, large cells in all cases and few small cells were reactive for cytokeratin (CK) and vimentin (VIM). Epithelial membrane antigen was observed in large cells in three cases, four cases expressed Leu 7 antigen, three were focally positive for glial fibrillary acidic protein, one for desmin, and one for chromogranin. All cases were nonreactive for retinol-binding protein, neurofilaments, alpha-fetoprotein, S-100 protein, and carcinoembryonic antigen. Five normal adult retinas were studied similarly; the pigmented epithelium of the retina was reactive for CK, VIM, HMB45, NSE, and S-100. DNA study, performed in eight tumors, revealed aneuploidy in two (DNA index = 1.7 and 1.8); these cases recurred within 1 month. No differences were observed according to site or behavior. MNTI is a primitive neuroectodermal tumor with polyphenotypic expression of neural and epithelial markers, melanin production, occasional glial, and rhabdomyoblastic differentiation, and no photoreceptor differentiation. It probably represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.
Asunto(s)
Epidídimo , Neoplasias Mandibulares/patología , Neoplasias Maxilares/patología , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/patología , Niño , Preescolar , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Masculino , Neoplasias Mandibulares/metabolismo , Neoplasias Mandibulares/ultraestructura , Neoplasias Maxilares/metabolismo , Neoplasias Maxilares/ultraestructura , Microscopía Electrónica , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/ultraestructura , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/ultraestructura , Tomografía Computarizada por Rayos XRESUMEN
The occurrence of Adams-Oliver syndrome in a patient from the same geographic area as the first reported kindred led to follow-up of the original family, and to a survey of the literature. Of 81 cases in 32 families, there is an approximately equal distribution between sexes (38 males: 43 females). Vertical transmission in at least 8 families is consistent with autosomal dominant inheritance. The phenotype is variable with a range of mild-to-severe defects of the scalp and/or underlying bone. Despite large defects of the cranium, central nervous system abnormalities have not been found and intellectual development appears to be normal. Limb defects are usually limited to the digits, but may involve the long bones and are entirely absent in some obligate carriers of the gene. Cutis marmorata and tortuous, dilated scalp veins have been reported in association with the major head and limb defects, but also in isolation as a forme fruste phenotype. Thus, there is a broad range of variable expression ranging from cases with lethally hemorrhagic cranial defects and/or severe limb malformations, to patients without any apparent manifestations. Despite a phenotypic resemblance to isolated aplasia cutis congenita and to the syndrome of terminal transverse limb defects, Adams-Oliver syndrome appears to be causally distinct. While the underlying pathophysiologic mechanism remains unknown, it can be speculated that cranial vertex defects and malformations of the limbs represent field defects resulting from impaired circulation in "watershed" areas during a critical period of development.
Asunto(s)
Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Cráneo/anomalías , Femenino , Estudios de Seguimiento , Deformidades Congénitas del Pie/diagnóstico por imagen , Deformidades Congénitas de la Mano/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Linaje , Fenotipo , Radiografía , Cuero Cabelludo/anomalías , Cuero Cabelludo/patología , Cráneo/diagnóstico por imagen , SíndromeRESUMEN
A patient with the Noonan-like/multiple giant cell lesion syndrome is reported and the findings in 14 cases are reviewed. Impressive manifestations include short stature, low normal intelligence or developmental delay, ocular hypertelorism, prominent posteriorly angulated ears, giant cell lesions of bones, joints, and/or soft tissues, pectus excavatum, and pulmonic stenosis. It has been difficult to delineate the syndrome because problems in identifying the condition have resulted from incomplete or truncate ascertainment by various medical specialists.
Asunto(s)
Anomalías Múltiples , Enfermedades Óseas , Enfermedades del Tejido Conjuntivo , Células Gigantes/patología , Síndrome de Noonan , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Adolescente , Enfermedades Óseas/genética , Enfermedades Óseas/patología , Enfermedades del Tejido Conjuntivo/genética , Enfermedades del Tejido Conjuntivo/patología , Femenino , Genes Dominantes/genética , Granuloma de Células Gigantes/genética , Granuloma de Células Gigantes/patología , Humanos , Masculino , Síndrome de Noonan/genética , Síndrome de Noonan/patología , Síndrome , Terminología como AsuntoRESUMEN
We have coined the term "pseudo-trisomy 13 syndrome" to designate cases of holoprosencephaly, severe facial anomalies, postaxial polydactyly, various other congenital defects, and normal chromosomes. Eleven instances are summarized. Two pairs of sibs and two other cases with consanguinity suggest autosomal recessive inheritance. Autosomal recessive inheritance is possible. Alternately, an undetected microdeletion and etiologic heterogeneity (some cases possibly representing dominant new mutations) must be considered. Further delineation is necessary. It is hoped that this paper will serve as a focus for further discussion of the problem.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 13 , Trisomía , Diagnóstico Diferencial , Femenino , Genes Recesivos , Holoprosencefalia/genética , Humanos , Recién Nacido , Masculino , Embarazo , SíndromeRESUMEN
Between 1965 and 1986 we saw 36 children with enuresis and urinary tract infection in association with "inversion" of facial expression when laughing. Urologic work-up of these patients disclosed characteristic findings of mild neuropathic bladder in all cases, with severe urinary tract damage in most of them. The clear association of distortion in facial expression and neuropathic bladder with resultant damage to the genitourinary tract should prompt urological evaluation of individuals with "inversion" of facial expression. About two thirds of the patients also had moderate to severe constipation. We suggest the term urofacial syndrome for this disorder. The occurrence of the disorder in multiple sibs, normal parents, increased parental consanguinity, and equal sex ratio indicate autosomal recessive inheritance.
Asunto(s)
Anomalías Múltiples/genética , Enuresis/genética , Expresión Facial , Vejiga Urinaria Neurogénica/genética , Niño , Estreñimiento/genética , Genes Recesivos , Humanos , Masculino , Linaje , Síndrome , Uremia/genéticaRESUMEN
The Yemenite deaf-blind hypopigmentation syndrome is a rare disorder characterized by severe early hearing loss, microcornea and colobomata, and cutaneous pigmentation abnormalities. A girl with similar skin symptoms and hearing loss, but no microcornea or colobomata is described and compared to other reported patients.
Asunto(s)
Sordera/complicaciones , Anomalías del Ojo/genética , Hipopigmentación/genética , Niño , Sordera/genética , Anomalías del Ojo/complicaciones , Femenino , Humanos , Hipopigmentación/complicaciones , Lactante , Recién Nacido , Discapacidades para el Aprendizaje/complicaciones , Discapacidades para el Aprendizaje/genética , Masculino , Hipertonía Muscular/complicaciones , Hipertonía Muscular/genética , Embarazo , SíndromeRESUMEN
Fewer than two dozen cases of frontometaphyseal dysplasia have been reported, some doubly or erroneously. In most reports, no information is available on possible variable manifestations in female relatives. Statements that the disorder is inherited as a dominant trait, and as an X-linked recessive have caused us to consider genetic heterogeneity. A recent large kindred prompted us to survey all published examples. We asked authors to reexamine the families they studied for any expression in relatives. In some cases, no further information could be elicited, but some additional information was gathered and pedigrees modified. This evidence was sufficient to indicate X-linked inheritance, with severe manifestations in males and extremely variable manifestations in females.
Asunto(s)
Enfermedades del Desarrollo Óseo/genética , Cromosomas Sexuales , Cromosoma X , Huesos Faciales/anomalías , Femenino , Ligamiento Genético , Pérdida Auditiva Bilateral/genética , Humanos , Masculino , Atrofia Muscular/genética , Linaje , Fenotipo , Estudios Retrospectivos , Factores SexualesRESUMEN
Oblique facial clefts are rare and include types 2-6 of Tessier's classification. Here we report on 4 patients with oblique facial clefts and a strikingly similar facial appearance. The pattern of facial involvement, the presence of consanguinity in 3 of them, as well as the entire clinical picture, suggest a unique dysmorphogenetic process which could represent, in some instances, an oculomaxillofacial dysostosis.
Asunto(s)
Anomalías Múltiples/patología , Anomalías del Ojo/patología , Huesos Faciales/anomalías , Anomalías Múltiples/etiología , Anomalías Múltiples/genética , Síndrome de Bandas Amnióticas/complicaciones , Fisura del Paladar/etiología , Consanguinidad , Disostosis Craneofacial/clasificación , Femenino , Genes Recesivos , Heterogeneidad Genética , Humanos , Recién Nacido , MasculinoRESUMEN
The GAPO syndrome is a rare but distinct autosomal-recessive disorder. The term GAPO is an acronym for the manifestations of Growth retardation. Alopecia, Pseudo- anodontia (failure of tooth eruption), and progressive Optic atrophy. We are aware of five other published patients. All have a strikingly similar appearance. This, along with other distinct manifestations, should allow clear differentiation from other causes of growth retardation. The hypothesis of autosomal-recessive inheritance is based on parental consanguinity and affected sibs in several cases.
Asunto(s)
Alopecia/genética , Enanismo/genética , Boca Edéntula/genética , Atrofia Óptica/genética , Niño , Consanguinidad , Femenino , Humanos , Síndrome , Erupción DentalRESUMEN
We report on a family of seven affected with a new syndrome of multiple deep schwannomas, multiple nevi (both intradermal and compound types), and multiple leiomyomas of the vagina. Inheritance is dominant, whether autosomal or X-linked cannot be determined at this time. The nevi, which are congenital, appear to be a marker for the syndrome. Both the schwannomas and leiomyomas do not manifest until adulthood.
Asunto(s)
Leiomioma/genética , Neoplasias Primarias Múltiples/genética , Síndromes Neoplásicos Hereditarios/genética , Neurilemoma/genética , Nevo/genética , Neoplasias Cutáneas/genética , Neoplasias Vaginales/genética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurilemoma/patología , LinajeRESUMEN
Melnick-Needles syndrome is an X-linked dominant trait, lethal in males. There are three well-documented lethal examples of the disorder in the offspring of affected females and three examples in males born to normal parents who represent new mutations.
Asunto(s)
Osteocondrodisplasias/genética , Preescolar , Cara/anomalías , Genes Dominantes , Genes Letales , Ligamiento Genético , Humanos , Masculino , Osteocondrodisplasias/diagnóstico por imagen , Radiografía , Cromosoma XRESUMEN
We identified a phenotypically normal obligate heterozygote for Hurler syndrome with exceedingly low levels of alpha-L-iduronidase enzyme activity. Subsequent investigation determined that low alpha-L-iduronidase activity was systemic, also characteristic of the subject's leukocytes and cultured skin fibroblasts. Residual alpha-L-iduronidase activity of cultured fibroblasts was found to have reduced catalytic activity (Vmax) against the 4-methylumbelliferone substrate, but normal substrate affinity (KM). Additional studies further characterized the residual enzyme activity in this woman who is an apparent compound heterozygote for Hurler syndrome, and for an allele with low alpha-L-iduronidase activity lacking pathologic manifestation. Such low activity "pseudodeficiency" alleles will complicate attempts at prenatal diagnosis of Hurler syndrome and related disorders in rare families.
Asunto(s)
Alelos , Glicósido Hidrolasas/metabolismo , Iduronidasa/metabolismo , Mucopolisacaridosis I/genética , Diagnóstico Prenatal , Adulto , Niño , Femenino , Humanos , Masculino , Mucopolisacaridosis I/enzimología , Linaje , Fenotipo , EmbarazoRESUMEN
The term ermine phenotype has been chosen to describe patients with white hair with black tufts. The patients also have sensorineural hearing loss. This rare phenotype may come about either by failure of migration of melanocytes or by an autoimmune mechanism. Examples of each are cited. The authors describe a possible third type. Comparison with other pigment loss-sensorineural hearing loss syndromes is made.
Asunto(s)
Pérdida Auditiva Sensorineural/genética , Trastornos de la Pigmentación/genética , Adulto , Femenino , Pérdida Auditiva Sensorineural/complicaciones , Humanos , Fenotipo , Trastornos de la Pigmentación/complicaciones , SíndromeRESUMEN
Analysis of the literature yielded 42 examples of the combination of sternal non-union and supraumbilical raphé without evidence of sex predilection. However, among an additional 31 cases in which the triad included facial hemangioma, there was almost exclusive female occurrence. Another condition involves extensive unilateral hemangioma of the face, absence of ipsilateral carotid and vertebral vessels, mental retardation, and Dandy-Walker malformation. Still another disorder has been proposed which includes facial hemangioma and dilatation of the carotid syphon. Both of these conditions exhibit marked female predilection. Examples of overlap of all three "disorders" cause the authors to question the independence of these disorders, hypothesizing instead that they represent a spectrum.
Asunto(s)
Abdomen/anomalías , Anomalías Múltiples/epidemiología , Arterias/anomalías , Síndrome de Dandy-Walker/epidemiología , Neoplasias Faciales/epidemiología , Hemangioma/epidemiología , Discapacidad Intelectual/epidemiología , Esternón/anomalías , Arterias Carótidas/anomalías , Arterias Cerebrales/anomalías , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Distribución por Sexo , SíndromeRESUMEN
Since the description by de la Chapelle and colleagues of two sibs with a unique skeletal dysplasia, two additional cases have occurred, one in the original Finnish family and one sporadic patient born to unrelated parents of Belgian descent. The original Finnish family has later had a fourth child, a normal daughter who was found to be unaffected upon radiographic examination in the 19th week of gestation. These additional findings are compatible with recessive inheritance. Physical features common to these four patients include cleft palate, small thorax, moderately severe micromelia with small hands, and equinovarus deformity. In each case, the ulnae and fibulae were reduced to an almost triangular osseous remnant. Other long bones were short and bowed. Neonatal death occurred in all cases and may be attributed to a consistent triad of respiratory tract malformations: laryngeal stenosis, tracheobronchomalacia, and pulmonary hypoplasia. Clinical and radiographic features are sufficiently unique to distinguish de la Chapelle dysplasia from other disorders in the spectrum of neonatal lethal osteochondrodysplasias. Lacunar halos were identified as a distinctive histopathologic feature also observed in achondrogenesis but not in several other skeletal dysplasias.
Asunto(s)
Osteocondrodisplasias/genética , Bélgica/etnología , Consanguinidad , Diagnóstico Diferencial , Femenino , Finlandia , Genes Recesivos , Humanos , Recién Nacido , Masculino , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/patología , Fenotipo , Diagnóstico Prenatal , RadiografíaRESUMEN
A new type of mesomelic dysplasia was in 3 generations of a large Thai family. It is characterized by bilateral symmetrical marked shortening of the ulnae and shortening and bowing of the radii. The proximal fibula is usually short and synostoses are present between the tibia and fibula and the small malformed calcaneus and talus. The prominent calcanei on the ventral surfaces of the distal fibulae are a characteristic feature of the new type. Carpal and tarsal synostoses are present in some affected people. All affected individuals walk on the tips of their toes with the dorsal foot deviated laterally. The deformities of the radius and ulna somewhat resemble those of mesomelic dysplasia, Langer type, but otherwise the condition is distinctly different. This new mesomelic dysplasia is an autosomal dominant trait with complete penetrance and variable expressivity over 3 generations.