Spinal neurofibromatosis with central nervous system involvement in a set of twin girls and a boy: further expansion of the phenotype.

Background: Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations.

Objectives: The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature.

Methods And Results: In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature.

Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients.

The term twin spotting refers to phenotypes characterized by the spatial and temporal co-occurrence of two (or more) different nevi arranged in variable cutaneous patterns, and can be associated with extra-cutaneous anomalies. Several examples of twin spotting have been described in humans including nevus vascularis mixtus, cutis tricolor, lesions of overgrowth, and deficient growth in Proteus and Elattoproteus syndromes, epidermolytic hyperkeratosis of Brocq, and the so-called phacomatoses pigmentovascularis and pigmentokeratotica. We report on a 28-year-old man and a 15-year-old girl, who presented with a previously unrecognized association of paired cutaneous vascular nevi of the telangiectaticus and anemicus types (naevus vascularis mixtus) distributed in a mosaic pattern on the face (in both patients) and over the entire body (in the man) and a complex brain malformation (in both patients) consisting of cerebral hemiatrophy, hypoplasia of the cerebral vessels and homolateral hypertrophy of the skull and sinuses (known as Dyke-Davidoff-Masson malformation).

SMN1 gene copy number analyses for SMA healthy carriers in Italian population.

The routine molecular test for spinal muscular atrophy (SMA) diagnosis is based on the detection of a homozygous deletion of exons 7 and 8 of the telomeric copy of the survival motor neuron gene (SMN1). The presence of the centromeric copy of the SMN gene (SMN2) does not allow the detection of the hemizygous absence of the SMN1 gene, which characterizes the disease carriers. The demand for a quantitative SMN1 test is permanently growing because there is a high incidence of carriers.

A novel NF1 gene mutation in an Italian family with neurofibromatosis type 1.

Purpose: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an estimated incidence of one in 3,500 births. Clinically, NF1 is characterized by café-au-lait (CAL) spots, neurofibromas, freckling of the axillary or inguinal region, Lisch nodules, optic nerve glioma, and bone dysplasias. NF1 is caused by inactivating mutations of the 17q11.

Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia.

Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12-18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified.

Neurofibromatosis type 1 and infantile spasms.

Background: There is no agreement on the prevalence, natural history and outcome of infantile spasms (IS) in neurofibromatosis type 1 (NF1). By contrast, its prevalence and outcome are well characterised in the setting of other neurocutaneous disorders (e.g.

A novel point mutation in PMP22 gene in an Italian family with hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder characterized by recurrent sensory or motor dysfunction. In 85% of HNPP cases the genetic defect is a 1.4 Mb deletion on chromosome 17p11.

Putative role of specific JAG1 gene exons in modulating clinical features in patients with leukoencephalopathy.

The aim of this study was to investigate the possible role of JAG1 gene mutations in modulating clinical features in patients with CADASIL-like phenotype which resulted negative for NOTCH3 gene mutations. Sixty-six CADASIL-like patients without NOTCH3 gene mutations were investigated for 5 out of 26 exons of the JAG1 gene, whose mutations were implicated in central nervous system vascular abnormalities. PCR was performed with primers specific for exons 3, 4, 13, 23 and 24 comprising the intron-exon boundaries.

Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia.

Spastic paraplegia type 4 is caused by mutations in the gene that encodes spastin (SPG4), a member of the AAA protein family. A cohort of 34 unrelated Italian patients with pure spastic paraplegia, of which 18 displayed autosomal dominant inheritance and 16 were apparently sporadic, were screened for mutations in the SPG4 gene by denaturing high performance liquid chromatography. We identified a previously reported mutation in a sporadic patient with pure hereditary spastic paraplegia.

Comparison of different techniques for detecting 17p12 duplication in CMT1A.

Charcot-Marie-Tooth type 1A is caused by a 1.5Mb DNA duplication in the 17p12 chromosomal region encompassing the peripheral myelin protein 22 gene. In the present study, we compared the Real-Time PCR with the other methods currently used for the diagnosis of Charcot-Marie-Tooth.

Further evidence of genetic heterogeneity in autosomal dominant distal motor neuronopathy.

Distal hereditary motor neuronopathy is a genetically and clinically heterogeneous disorder. To date, five loci, and their relative genes, have been mapped on chromosomes 7p14, 7q11, 9q34, 11q12 and 12q24, respectively. We describe an Italian family with autosomal dominant distal HMN starting at around 30 years of age with weakness and atrophy of distal leg muscles and pyramidal features.

A simple method for diagnosis of autosomal recessive spinal muscular atrophy by denaturing high-performance liquid chromatography.

Autosomal recessive spinal muscular atrophy is caused by mutations in the survival motoneuron (SMN) gene. There are two nearly identical copies of this gene present on chromosome 5q13; however, only the telomeric copy of this gene is affected in spinal muscular atrophy. In this study, we describe a new method to detect SMN gene deletion by denaturing high-performance liquid chromatography, which is also simple to perform but is faster and more specific.

A large family with pure autosomal dominant hereditary spastic paraplegia from southern Italy mapping to chromosome 14q11.2-q24.3.

A large Italian pedigree from southern Italy with autosomal dominant uncomplicated spastic paraplegia is reported. The clinical picture was uniform and characterized by insidiously progressive lower extremity weakness and spasticity. The mean age at onset of symptoms was 8.

A novel mutation in the CLN1 gene in a patient with juvenile neuronal ceroid lipofuscinosis.

We describe the clinical, neuropathological and molecular findings from a patient affected with neuronal ceroid lipofuscinosis with a juvenile onset (JNCL). She was a 9-year-old right-handed girl with a normal birth and early developmental milestones. At the age of 4 the early symptoms began.