Pituitary deficiency and congenital infiltrating lipomatosis of the face in a girl with deletion of chromosome 1q24.3q31.1.

Interstitial deletions of the long arm of chromosome 1 are rare and they are classified as proximal or intermediate. The intermediate interstitial deletions span 1q24-1q32. We describe a 6-year-old girl with multiple pituitary hormone deficiency, severe cognitive impairment, bilateral cleft lip and palate, midline facial capillary malformation, erythema of hands and feet and dysplastic cranial vessels, low anti-thrombin III activity, hemifacial overgrowth due to progressive infiltrating lipomatosis with bone overgrowth, marked vascular proliferation and erythema of hands and feet, and abnormal cranial vessels. The girl's karyotype showed an apparently de novo interstitial deletion 1q24.3q31.1, which was defined by array-CGH. The deleted region contains numerous genes, but only eight (CENPL, LHX4, LAMC1, LAMC2, PTGS2, ANGPTL1, TNN, and TNR) are good candidates to explain, at least partially, the phenotype of the proposita. We, therefore, discuss the involvement of these genes and the observed phenotype.

Scoliosis with cognitive impairment in a girl with 8q11.21q11.23 microdeletion and SNTG1 disruption.

Idiopathic scoliosis (IS) is an abnormality of the vertebral column with a spine curvature of at least 10 degrees. It is the most common spinal deformity in children with a prevalence of 2%-3%, and its aetiology is unknown. Genetic factors are known to play a role and a number of linkage analyses showed associations of various loci. Here we describe a new case of a de novo interstitial deletion 8q11.21q11.2 disrupting SNTG1 gene, identified by array-CGH in a girl with cognitive impairment and a scoliosis that 'appears' like to IS. SNTG1 encodes γ-1 Syntrophin protein that is part of the dystrophin associated protein complex and interacts directly with the C-terminal of dystrophin. Its expression is restricted to neurons and particularly in those areas of the brain that have been suggested to affect postural control. The involvement of SNTG1 gene in IS was already been reported in a family with a breakpoint between exons 10 and 11. Mutational analysis of SNTG1 exons in 152 sporadic IS patients had revealed changes in three patients. In conclusion, our data add a further line of evidence suggesting SNTG1 could represent an interesting candidate for its involvement in scoliosis.

17q23.3 de novo microdeletion involving only TANC2 gene: A new case.

Neurodevelopmental disorders (NDDs) show a wide range of overlapping clinical features. Intellectual disability (ID), developmental delay (DD), autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), language and communication disorders with or without motor abnormalities and/or epilepsy have been reported associated to single or multiple genes but in many cases the genetic basis remains unknown. The increasingly use of array-CGH has significantly improved the yield of diagnosing genomic disorders and led to the identification of several novel microdeletion and microduplication syndromes. TANC2 encodes a synaptic scaffold protein interacting with multiple neuropsychiatric disorder-related postsynaptic density (PSD) proteins in dendrites. Here, we describe a new case of TANC2 gene disruption in a 17q23.3 de novo microdeletion identified by array-CGH. The patient presented craniofacial dysmorphic features, hypotonia, and severe cognitive and motor impairment. In conclusion, our data add a further line of evidence supporting the role of TANC2 in NDDs and will help further researches to elucidate the regulatory mechanism of synaptic function and plasticity related to TANC2 haploinsufficiency.

Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

Clinical and molecular delineation of a 16p13.2p13.13 microduplication.

The 16p13.3p13.1 region has been reported as a "critical" hotspot region for recurrent microdeletions/duplications, which may contribute to epilepsy, learning difficulties and facial dysmorphisms. Cytogenetic and array-CGH analyses were performed because of the clinical characteristics of the patient. The girl showed de novo 16p13.3p13.13 duplication spanning a region of ∼5.3 Mb. She presented brain anomalies, intellectual disability, epilepsy, facial and vertebral dysmorphisms. To our knowledge, this is the first reported case of 16p13.3p13.13 duplication; only three patients with an overlapping deletion in 16p13.2p13.13 were previously described. The duplicated region contains 21 OMIM genes and, six of them (RBFOX1, TMEM114, ABAT, PMM2, GRIN2A and, LITAF) were found to be associated with known diseases. Although no duplication of these genes has been described in the literature, we discuss here if they had some role in determining phenotype of our patient.

Molecular cytogenetic characterization of the first reported case of an inv dup (4p)(p15.1-pter) with a concomitant 4q35.1-qter deletion and normal parents.

Inverted duplications associated with terminal deletions are complex anomalies described in an increasing of chromosome ends. We report on the cytogenetic characterization of the first de novo inv dup del(4) with partial 4p duplication and 4q deletion in a girl with clinical signs consistent with "recombinant 4 syndrome". This abnormality was suspected by banding, but high-resolution molecular cytogenetic investigations allowed us to define the breakpoints of the rearrangement. The terminal duplicated region extending from 4p15.1 to the telomere was estimated to be 29.27 Mb, while the size of the terminal deletion was 3.114 Mb in the 4q35.1 region. Until now, 10 patients with duplicated 4p14-p15 and deleted 4q35 chromosome 4 have been described. In all cases the abnormal chromosome 4 was derived from a pericentric inversion inherited from one of the parents. In conclusion, we have identified the first case of inv dup del(4) with normal parents suggesting that, often, terminal duplications or terminal deletions mask complex rearrangements.