RESUMEN
We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases.
Asunto(s)
Síndrome de Beckwith-Wiedemann/genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Metilación de ADN , Desarrollo Fetal/genética , Impresión Genómica , Disomía Uniparental , Antropometría , Síndrome de Beckwith-Wiedemann/clasificación , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/patología , Cromosomas Humanos Par 11/química , Feto , Expresión Génica , Genotipo , Edad Gestacional , Humanos , Recién Nacido , Mutación , Fenotipo , Nacimiento PrematuroRESUMEN
Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.
Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Proteínas de Unión al ADN/genética , Cara/anomalías , Estudios de Asociación Genética , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/genética , Mutación , Proteínas de Neoplasias/genética , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/genética , Facies , Femenino , Humanos , Masculino , Fenotipo , Análisis de Secuencia de ADNRESUMEN
The mild activity of basaltic volcanoes is punctuated by violent explosive eruptions that occur without obvious precursors. Modelling the source processes of these sudden blasts is challenging. Here, we use two decades of ground deformation (tilt) records from Stromboli volcano to shed light, with unprecedented detail, on the short-term (minute-scale) conduit processes that drive such violent volcanic eruptions. We find that explosive eruptions, with source parameters spanning seven orders of magnitude, all share a common pre-blast ground inflation trend. We explain this exponential inflation using a model in which pressure build-up is caused by the rapid expansion of volatile-rich magma rising from depth into a shallow (<400 m) resident magma conduit. We show that the duration and amplitude of this inflation trend scales with the eruption magnitude, indicating that the explosive dynamics obey the same (scale-invariant) conduit process. This scale-invariance of pre-explosion ground deformation may usher in a new era of short-term eruption forecasting.
RESUMEN
Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome is an autosomal dominant form of ectodermal dysplasia associated with limb anomalies and orofacial clefting. The TP63 gene has been shown to be the cause of the disease, and some tentative genotype-phenotype correlations have been reported. We describe a familial case of EEC syndrome, diagnosed in two siblings affected by severe ectrodactyly and mild ectodermal dysplasia, without clefting. Moreover, one of the siblings had a history of delayed developmental milestones in the first years of life. Family history revealed mild hand malformations in the father and grandfather, who were not available for clinical evaluation. The TP63 gene molecular study showed in both siblings a heterozygous H208D mutation, which has not been previously reported to our knowledge, suggesting that this molecular lesion is associated with EEC syndrome without orofacial clefting.
Asunto(s)
Displasia Ectodérmica/genética , Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Mutación/genética , Transactivadores/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Niño , Labio Leporino/genética , Fisura del Paladar/genética , Femenino , Genotipo , Humanos , Masculino , Fenotipo , Hermanos , Factores de TranscripciónRESUMEN
We describe a girl with Niikawa-Kuroki (Kabuki) syndrome (NKS) with conical incisors, hypodontia, hypoplastic nails, and brittle hair. Abnormal teeth are common in NKS and support a hypothesis of autosomal dominant inheritance of the syndrome [Halal et al., 1989; Silengo et al., 1996]. Hair abnormalities have never been investigated in NKS. The ectodermal involvement in NKS could represent an important clue for the understanding of the pathogenesis of this syndrome.
Asunto(s)
Anomalías Múltiples/patología , Anodoncia/patología , Huesos/anomalías , Niño , Cara/anomalías , Femenino , Cabello/anomalías , Pérdida Auditiva Sensorineural/genética , Humanos , Incisivo/anomalías , Discapacidad Intelectual/genética , Uñas Malformadas , SíndromeRESUMEN
Four unrelated cases of congenital diaphragmatic hernia associated with ipsilateral upper limb reduction defects were reported by McCredie and Reid in 1978 (J Pediatr 92: 762-765). As contiguous segments of the cervical neural crest are involved in the development of diaphragm and arms, the authors suggested that an early injury to the cervical neural crest might be the common underlying pathogenesis. We describe here a further example of this malformation complex: a newborn with a left posterolateral diaphragmatic hernia associated with ipsilateral thumb hypoplasia.
Asunto(s)
Anomalías Múltiples/embriología , Hernias Diafragmáticas Congénitas , Radio (Anatomía)/anomalías , Pulgar/anomalías , Dermatoglifia , Parálisis Facial/complicaciones , Parálisis Facial/congénito , Hernia Diafragmática/embriología , Hernia Diafragmática/epidemiología , Humanos , Incidencia , Recién Nacido , Masculino , Cresta Neural/patología , Radio (Anatomía)/embriologíaRESUMEN
We report on a girl with congenital hypoplastic anaemia, "coarse" face, generalized hypertrichosis with scalp hypotrichosis, short fifth finger, hypoplastic toenails, and mental retardation. A sister of the proposita, who died at the age of 1 year, had severe congenital anaemia, hypoplastic fingernails, low birth weight, failure to thrive, and repeated upper respiratory tract infections. Based on family history, we suspect that hypoplastic anaemia and the same multiple congenital anomalies-mental retardation syndrome (MCA/MR) were also present in this sister. To the best of our knowledge, this patient represents the first report of congenital hypoplastic anaemia and such a complex MCA/MR syndrome, probably inherited as an autosomal recessive trait.
Asunto(s)
Anomalías Múltiples/patología , Anemia de Fanconi/patología , Discapacidad Intelectual/patología , Anomalías Múltiples/genética , Niño , Preescolar , Cromosomas Humanos Par 19/genética , Anemia de Fanconi/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Lactante , Discapacidad Intelectual/genética , SíndromeRESUMEN
A 2-year-old boy with features suggestive of cri-du-chat syndrome had a complex karyotype: 45,XY,--22,5p--,t(5p:22q). Clinical symptoms were catlike cry in early infancy, severe mental and motor retardation, failure to thrive, hypertelorism, antimongoloid slant of the eyes, ptosis of the eyelids, epicanthus, micrognathia, dermatoglyphics abnormalities, and partial syndactyly between 2nd and 3rd toes.
Asunto(s)
Aneuploidia , Aberraciones Cromosómicas , Cromosomas Humanos 21-22 e Y , Cromosomas Humanos 4-5 , Síndrome del Maullido del Gato/genética , Translocación Genética , Preescolar , Humanos , Masculino , FenotipoRESUMEN
Most reported cases of Conradi-Hünermann disease are said to be sporadic. The diagnostic radiographic features present in early life tend to disappear with age. Skeletal deformities may persist but are not adequate for diagnosis. It is critical that the examiner look for nonskeletal manifestations of the disease, particularly eye and skin changes, in parents and relatives before assuming that the proband represents a sporadic case. Some of the sporadic cases may also be accounted for by the existence of environmental phenocopies. The proband's mother in the family described in this paper was recognized as a carrier of the gene only after careful eye and skin examination. This observation was particularly important because she was pregnant at the time. Her 16-week-old fetus is the earliest documented example of the disease. Autosomal dominant mode of inheritance is suggested by the familial cases, but the variability of expression could be the result of either genetic or clinical heterogeneity. Sex-influenced factors may account for the different severity of the disease in the two sexes.
Asunto(s)
Condrodisplasia Punctata/genética , Adulto , Huesos/diagnóstico por imagen , Preescolar , Condrodisplasia Punctata/diagnóstico , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Manifestaciones Oculares , Femenino , Enfermedades Fetales/diagnóstico por imagen , Regulación de la Expresión Génica , Genes Dominantes , Ligamiento Genético , Humanos , Embarazo , Radiografía , Factores Sexuales , Manifestaciones Cutáneas , SíndromeRESUMEN
Radiological study may prompt the correct diagnosis of Trisomy 8 mosaicism when the clinical features are mild and could be overlook. Skeletal features characteristic of Trisomy 8 are found in the skull, elbows, spine, pelvis, hands and feet.
Asunto(s)
Huesos/diagnóstico por imagen , Cromosomas Humanos 6-12 y X , Mosaicismo , Trisomía , Niño , Humanos , Masculino , RadiografíaRESUMEN
An 8-year-old male with mental retardation, speech difficulties, and minor congenital anomalies is presented. The clinical findings suggest the trisomy-8 syndrome. The karyotype indicates trisomy-8 mosaicism with trisomic as well as normal cell lines in blood lymphocytes.
Asunto(s)
Cromosomas Humanos 6-12 y X , Discapacidad Intelectual/genética , Mosaicismo , Trisomía , Niño , Cromosomas , Anomalías Congénitas/genética , Humanos , Cariotipificación , Desarrollo del Lenguaje , Linfocitos/ultraestructura , MasculinoRESUMEN
Two sisters with spondylocastal dysostosis are presented. Clinical findings are: short neck, short trunk, decreased upper to lower segment ratio, vertebral and costal malformations and normal intelligence. Both the clinical aspects and the family history are suggestive of the autosomal recessive form of the disease.
Asunto(s)
Enfermedades del Desarrollo Óseo/genética , Costillas , Enfermedades de la Columna Vertebral/genética , Adolescente , Enfermedades del Desarrollo Óseo/diagnóstico por imagen , Niño , Femenino , Genes Recesivos , Humanos , Osificación Heterotópica , Radiografía , Costillas/diagnóstico por imagen , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagenRESUMEN
A nine day old boy who had the Pierre Robin syndrome also had an unusual associated hand malformation consisting of bilateral clinodactyly of the index finger. A supernumerary phalanx was inserted between the second metacarpal and the proximal phalanx of both index fingers with a radial deviation of the same phalanx. The same hand malformation has been previously described in three patients who had either the Pierre Robin syndrome or isolated cleft palate. On the basis of ours and the three previous cases, the existence of a new palato-digital syndrome is suggested.
Asunto(s)
Fisura del Paladar , Dedos/anomalías , Micrognatismo , Humanos , Recién Nacido , Masculino , Síndrome , Lengua/anomalíasRESUMEN
In 1982, Nadol & Burgess reported a new syndrome of cataract and progressive sensorineural hearing loss, inherited in an autosomal dominant fashion. Extensive histopathologic studies of the inner ear of the proband revealed severe cochleosaccular degeneration. No other sporadic or familial cases of such a genetic syndrome have subsequently been described. We report here a second family in which the syndrome of cataract and progressive sensorineural deafness is observed in eight members, and is inherited according to an autosomal dominant pattern.
Asunto(s)
Catarata/genética , Pérdida Auditiva Sensorineural/genética , Preescolar , Femenino , Genes Dominantes , Humanos , Linaje , SíndromeRESUMEN
Two unrelated children with partial deletion of the long arm of a chromosome no. 5 are reported. The boy presented with severe hypotonia, developmental delay, and a few minor defects of the face including frontal bossing, antimongoloid slant of the palpebral fissures, depressed nasal bridge and bilateral epicanthal folds. With age, his hypotonia has improved. The parents have normal chromosomes; the mother has a 9qh+ variant. The second patient, a girl, presented at birth with multiple congenital anomalies including cleft palate, epicanthal folds, anteverted nostrils, horseshoe kidneys and club feet. At 4 years of age, she was small and severely retarded. The normal parents and the normal sister showed no chromosomal abnormalities. Gene mapping studies in both patients failed to define a specific gene locus to the deleted chromosome regions. Including these two patients, there appear to be only three reported cases of patients with 5q deletion. A comparative description of the third patient is included in this report. There are some clinical similarities but these are inadequate to identify a clinical syndrome. This perhaps is explained by some quantitative and qualitative differences in the deletions.
Asunto(s)
Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos 4-5 , Discapacidad Intelectual/genética , Preescolar , Bandeo Cromosómico , Femenino , Humanos , MasculinoRESUMEN
Two patients with triphalangeal thumbs-ectrodactyly syndrome are described. The first case is a 4-year-old female with triphalangeal thumbs, preaxial polydactyly with rudimentary polydactyly of the 3rd finger of the right hand and ectro-syndactyly of feet. Her stillborn sister had triphalangeal thumbs and ectrodactyly of feet. The mother has triphalangeal thumbs, brachy-syndactyly of the left foot and ectro-syndactyly of the right one. The maternal grandmother has syndactyly of 1st, 2nd, 3rd toes and hypoplasia of the 3rd toe on the right foot. The second case is sporadic and shows triphalangeal thumbs, preaxial polydactyly of the right hand and bilateral lobster-claw feet. Our observations confirm the variability of clinical expression and support the autosomal dominant inheritance of the syndrome.
Asunto(s)
Anomalías Múltiples/genética , Pulgar/anomalías , Dedos del Pie/anomalías , Preescolar , Femenino , Genes Dominantes , Humanos , Recién Nacido , Linaje , Radiografía , Síndrome , Pulgar/diagnóstico por imagen , Dedos del Pie/diagnóstico por imagenRESUMEN
Two patients with the oro-facial-digital syndrome II or Mohr syndrome presented laryngeal anomalies and hallucal and postaxial polysyndactyly of the feet. Those rare malformations are typically observed in patients with the Majewski syndrome, a lethal, short rib-polydactyly skeletal dysplasia with orofacial findings almost identical to those of the Mohr syndrome. Phenotypic overlap between the Mohr and the Majewski syndromes has already been reported in the literature, and it has been suggested that the two syndromes may be mild and severe expressions of the same autosomal recessive disorder. Our two cases give further support to this hypothesis.
Asunto(s)
Anomalías Múltiples/clasificación , Síndromes Orofaciodigitales/clasificación , Osteocondrodisplasias/clasificación , Síndrome de Costilla Pequeña y Polidactilia/clasificación , Preescolar , Femenino , Deformidades Congénitas del Pie , Deformidades Congénitas de la Mano , Humanos , Lactante , Laringe/anomalías , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Fenotipo , Síndrome de Costilla Pequeña y Polidactilia/diagnóstico , Síndrome de Costilla Pequeña y Polidactilia/genéticaRESUMEN
The association of upper limb malformations and congenital cardiac anomalies was established as a definite clinical and genetic entity by Holt & Oram in 1960. Significant variability of malformations in both the upper limbs and the cardiovascular system has been well documented. In 1978, Temtamy & McKusick reported a family studied by Tabatznik, in which upper limb deformities, including type D brachydactyly, occurred in association with cardiac arrhythmias as a dominant, either autosomal or X-linked trait. They called this apparently new entity "Heart-Hand syndrome II" to distinguish it from the Holt-Oram syndrome. No other similar cases have subsequently been reported. We describe here the second family affected with the Tabatznik syndrome and add some new findings to the clinical spectrum of this condition.
Asunto(s)
Deformidades Congénitas de la Mano/genética , Cardiopatías Congénitas/genética , Anomalías Múltiples/genética , Adulto , Arritmias Cardíacas/genética , Huesos del Carpo/anomalías , Niño , Preescolar , Bandeo Cromosómico , Criptorquidismo/genética , Femenino , Humanos , Masculino , Linaje , Síndrome , Pulgar/anomalíasRESUMEN
We report on an infant male who presented with microcephaly of prenatal onset, schizencephaly, decorticated disturbance of the neurological function, congenital optic atrophy, abnormal eye movements and nystagmus. In addition, he had a skeletal dysplasia with predominant acromelic involvement and a renal disease characterized by both nephritic and nephrotic changes. The natural history of his condition included severe postnatal failure to thrive, lack of development of psychomotor milestones, intractable seizures, terminal renal insufficiency with early death. Such spectrum of phenotypic abnormalities has never been reported before and we suggest that it may represent a new syndromic entity. The differential diagnosis with the oculo-skeletal-renal syndromes, with the osteodysplastic primordial dwarfism of the Taybi-Linder type and with the Hutterite cerebro-osteo-nephrodysplasia, is discussed.
Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Huesos/anomalías , Síndrome Oculocerebrorrenal , Huesos/diagnóstico por imagen , Humanos , Lactante , Masculino , Síndrome Oculocerebrorrenal/diagnóstico por imagen , RadiografíaRESUMEN
A 46,XX/46,XX,del(20)(p11) mosaicism was identified in a 10-month-old female infant with multiple congenital anomalies, development retardation and failure to thrive. The 20p partial deletion was observed in 50% of the cells examined. Both parents had normal phenotype and karyotype. Only four other patients with partial 20p deletion are known and they are not mosaics. Their clinical findings are similar to those of our patient; in particular, they share anomalies of the vertebral column such as segmentation errors and "butterfly-shaped" vertebrae.