Ground deformation reveals the scale-invariant conduit dynamics driving explosive basaltic eruptions.

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.

Fetal growth patterns in Beckwith-Wiedemann syndrome.

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.

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

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.

A novel H208D TP63 mutation in a familial case of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome without clefting.

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.

Congenital hypoplastic anaemia in a patient with a new multiple congenital anomalies-mental retardation syndrome.

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.

Ectodermal abnormalities in Kabuki syndrome.

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.

Congenital diaphragmatic hernia associated with ipsilateral upper limb reduction defects: report of a case with thumb hypoplasia.

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.

A syndrome of progressive sensorineural deafness and cataract inherited as an autosomal dominant trait.

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.

Oculocerebral syndrome with hypopigmentation (Cross syndrome): report of a new case.

A syndrome of ocular and cutaneous hypopigmentation, severe mental retardation with spastic tetraplegia and athetosis was first observed by Cross in three siblings of an inbred Amish family. Since then, seven other patients, three sporadic and four with familial recurrence, have been reported in the literature, confirming the autosomal recessive inheritance. The clinical spectrum of the syndrome has been expanded to include true developmental defects of the CNS such as cystic malformation of the posterior fossa of the Dandy-Walker type. We report a new case of Cross syndrome.

Heart-hand syndrome II. A report of Tabatznik syndrome with new findings.

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.

A new syndrome with cerebro-oculo-skeletal-renal involvement.

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.

Partial deletion of the short arm of chromosome 20: 46,XX,del(20)(p11)/46,XX mosaicism.

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.

Oro-facial-digital syndrome II. Transitional type between the Mohr and the Majewski syndromes: report of two new cases.

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.

Triphalangeal thumb and brachy-ectrodactyly syndrome. Confirmation of autosomal dominant inheritance.

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.

Asymmetric crying facies with microcephaly and mental retardation. An autosomal dominant syndrome with variable expressivity.

An infant boy with asymmetric crying facies, microcephaly, developmental retardation and failure to thrive is reported. His two siblings died in the newborn period because of complex congenital heart defects. The mother and the maternal grandmother have asymmetric crying facies, microcephaly and normal intelligence. A maternal aunt has severe physical and mental retardation, facial asymmetry, microcephaly, and cleft palate. This family allows an expansion of the spectrum of malformations associated with asymmetric crying facies and suggests autosomal dominant inheritance with variable expressivity.

Interstitial deletion of chromosome 1 (q23-q25). Report of a case.

We describe a 3-month-old female with a de novo interstitial deletion of the long arm of chromosome 1 (1q23-25). Clinical features are failure to thrive, psychomotor retardation, cleft lip and palate, short metacarpals, metatarsals and fingers and a severe congenital heart disease. The four previously reported patients with the same deletion share with ours the distinctive pattern of anomalies of the face and limbs; therefore, it seems now possible to delineate a proximal 1 q deletion syndrome.

The Neu-COFS (cerebro-oculo-facio-skeletal) syndrome: report of a case.

A newborn female with a phenotype intermediate between the Neu and the COFS syndromes is described. The hypothesis of the two conditions representing different degrees of severity of the same autosomal recessive mutation in the homozygote state is discussed.

Distinctive hair changes (pili torti) in Rapp-Hodgkin ectodermal dysplasia syndrome.

An 8-year-old girl with narrow nose, small mouth, maxillary hypoplasia, cleft palate, hypodontia and hypohidrosis is described. Her scalp hair was coarse, dry and wiry. Microscopic examination showed the hair to be twisted at irregular intervals on its long axis, as seen in pili torti. Her mother has the same features; as a child, she had identical hair and is now bald. Both mother and daughter display signs and symptoms of Rapp-Hodgkin's ectodermal dysplasia. The autosomal dominant inheritance of the disease is further supported by the findings in this family.