Cinzia Galasso

Deletion 2q37: An Identifiable Clinical Syndrome With Mental Retardation and Autism

Terminal deletion of the long arm of chromosome 2 is a rare chromosomal disorder characterized by low birth weight, delayed somatic and mental development, craniofacial defects, short neck, heart and lung congenital defects, and autistic features. We report on a girl with 46,XX.ish del(2)(q37.1) de novo karyotype, mental retardation, dysmorphic features, gastrointestinal anomalies, and autistic traits and compare her clinical manifestations with patients with the same deletion previously described in literature.

Twelve-hour Spontaneous Nocturnal Growth Hormone Secretion in Growth Retarded Patients

Twelve-hour nocturnal GH secretion was studied in 30 children with familial short stature (FSS), constitutional growth delay (CGD), total growth hormone deficiency (TGHD), partial growth hormone deficiency (PGHD), or idiopathic short stature (ISS). No difference was observed between subjects with FSS and children wtih CGD. The mean 12-hour serum GH concentration was significantly lower in patients with TGHD (p < 0.001), children with PGHD (p < 0.01), and subjects with ISS (p < 0.01) than in subjects with FSS and CGD. No overlap was observed between the range of mean concentration values of children with TGHD and that of subjects with FSS. A significant correlation was found between growth velocity expressed as SD from the mean for bone age and GH concentration (p < 0.001). All patients with a growth velocity <3rd percentile for bone age showed a mean nocturnal concentration <4 ng/ml. These data suggest that evaluation of 12-hour spontaneous nocturnal GH secretion with GH sampling every 30 minutes can be usefully employed in the diagnosis of GH deficiency.

A new case of Ambras syndrome associated with a paracentric inversion (8) (q12; q22)

Ambras syndrome (AS) is a special form of congenital universal hypertrichosis described for the first time by Baumeister et al. (1). This form differs from other forms of congenital hypertrichosis in the pattern of hair distribution and its associated anomalies. The molecular‐genetic cause of AS is unknown; the association of AS with a pericentric inversion (8) (p11.2; q22) described in the case of Baumeister so far has been unique in the literature. This report is the tenth with clinical signs of AS so far described in the literature and the second with an inversion in chromosome 8 and the first with evaluation of peripheral androgens. The new‐born girl presented with abundant and dark hair on the face and ears, on the shoulders and on the arms; the other parts of the body were covered with fine, lightly pigmented hair. The face showed many dysmorphic features. Chromosome analysis showed a paracentric inversion of one chromosome 8. The breakpoints were localised at q12 and q22. The parental karyotypes were normal. Laboratory investigation showed normal plasma levels of testosterone, androstenedione (A), 17‐hydroxyprogesterone, dehydroepiandrosterone‐sulphate (DHA‐S), free testosterone (FT), dihydrotestosterone (DHT) and 3α‐androstanediol‐glucuronide (3AG). Here we report a chromosomal inversion similar to that found previously not associated with alterations in androgen plasma levels.

Deletion 2p25.2: a cryptic chromosome abnormality in a patient with autism and mental retardation detected using aCGH.

We describe a 7-year-old patient with autism, moderate mental retardation, secondary microcephaly, agenesis of right optic nerve, and dysmorphic features carrying a de novo cryptic deletion of chromosome 2p25.2, detected by aCGH. Pure monosomies of 2p are very rare, and are usually observed as part of more complex aberrations involving other chromosomes. To the best of our knowledge, this is the first case presenting with a severe clinical phenotype and a de novo pure deletion of 2p25.2. The phenotypic effects of this rearrangement and the role of SOX11 gene, removed in our case, are herein discussed.

Cognitive and behavioral effects of new antiepileptic drugs in pediatric epilepsy

BACKGROUND In pediatric epilepsy, neurodevelopmental comorbidities could be sometimes even more disabling than seizures themselves, therefore it is crucial for the clinicians to understand how to benefit these children, and to choose the proper antiepileptic drug for the treatment of epilepsy associated to a specific neurodevelopmental disorder. Aim of this paper is to discuss the potential impact on cognition and behavior of new and newest AEDs and to guide the choice of the clinicians for a targeted use in epilepsy associated with specific neurodevelopmental disorders. METHODS Information in this review is mainly based on peer-reviewed medical publications from 2002 until October 2016 (PubMed). We choose to include in our review only the AEDs of second and third generation approved for pediatric population. RESULTS Vigabatrin, lamotrigine, topiramate, levetiracetam, oxcarbazepine, zonisamide, rufinamide, lacosamide, eslicarbazepine, and perampanel have been included in this review. The most tolerated AEDs from a cognitive and behavioral point of view are lamotrigine and rufinamide, thus representing optimal drugs for children with cognitive and/or attention problems. DISCUSSION Most of the new AEDs are initially licensed for adult patients. Data on children are usually very limited, both in terms of efficacy and safety, and the use standardized cognitive and behavioral outcome measures are very limited in pediatric clinical trials. CONCLUSION Several factors including polytherapy, administration of AEDs with the same mechanism of action and the dose and titration of the drug, should be considered as important in the development of cognitive and behavioral side effects.

Interstitial deletion of a proximal 3p: A clinically recognisable syndrome

Interstitial deletions of the proximal short arm of chromosome 3 occurring as constitutional aberrations are rare and a defined clinical phenotype is not established yet. We report on a 30-months-old girl with distinct facial features (square facies, plagiocephaly, broad forehead, broad nasal bridge, long philtrum and low set ears) and psychomotor/speech delay associated with an interstitial deletion of 3p12 chromosomal band, del(3)(p12p12). Clinical manifestations of our child were compared with those of other eight patients with the same deletion previously described to further delineate the proximal 3p deletion syndrome.

De novo mosaic ring chromosome 18 in a child with mental retardation, epilepsy and immunological problems

Ring chromosome 18 [r(18)] is a disorder in which one or both ends of chromosome 18 are lost and joined forming a ring-shaped figures. R(18) patients can therefore show features of 18q-, 18p- syndrome or a combination of both, depending on the size of the 18p and 18q deleted regions. The phenotype of the r(18) is characterized by developmental delay/mental retardation, typical facial dysmorphisms, major abnormalities and immunological problems. Here we report a case of de novo mosaic r(18) with a characterization by array-based comparative genomic hybridization analysis, and discuss the phenotypic correlation in r(18) also through a comparison with previously described cases of the literature.

Detecting anxiety symptoms in children and youths with neurofibromatosis type I

Children with Neurofibromatosis type 1 (NF1) are known to have cognitive, social, and behavioral deficits. Fifteen NF1‐subjects (5 boys, 10 girls, mean age = 13.4), and 15 healthy controls matched for age and sex were assessed on the presence of anxiety symptoms, using the Multidimensional Anxiety Scale for Children (MASC), self‐report questionnaire. Significant group differences emerged with regard to MASC total (Z = −2.058, P = 0.041) and anxiety disorder index (ADI; Z = −2.202, P = 0.026), but not with regard to single scales. When the severity and visibility of NF1 were considered, correlation between severity and social anxiety, and severity and MASC total was found. This is the first study assessing anxiety symptoms in NF1 children and youths. A precocious psychological survey and intervention in NF1 subjects, may contribute to reduce the risk of psychiatric disorders in adulthood.

Planning Deficit in Children With Neurofibromatosis Type 1: A Neurocognitive Trait Independent From Attention-Deficit Hyperactivity Disorder (ADHD)?

Neurofibromatosis type 1 is associated with executive dysfunctions and comorbidity with attention-deficit hyperactivity disorder (ADHD) in 30% to 50% of children. This study was designed to clarify the neurocognitive phenotype observed in neurofibromatosis type 1 by testing the hypothesis that children with neurofibromatosis type 1 have specific planning deficits independently from intellectual level and ADHD comorbidity. Eighteen children with neurofibromatosis type 1 were pair-matched to 18 children with ADHD and 18 healthy controls. All groups were assessed on the presence of ADHD symptoms (Conners Scales) and planning deficits (Tower of London). Compared with control group, groups with neurofibromatosis type 1 and ADHD demonstrated significant impairment of planning and problem solving. The lack of correlation between Tower of London results and Conners subscale scores in neurofibromatosis type 1 group confirmed that the planning and problem-solving deficit is not directly related to inattention level. These findings suggested that the executive impairment probably represents a peculiar trait of neurofibromatosis type 1 neurocognitive phenotype.

Late-onset epileptic spasms in children with Pallister-Killian syndrome: a report of two new cases and review of the electroclinical aspects.

Pallister-Killian syndrome is a rare syndrome of multiple congenital anomalies attributable to the presence of a mosaic supernumerary isochromosome (12p). Although the clinical manifestations of Pallister-Killian syndrome are variable, the most common anomalies include craniofacial dysmorphisms, limb deformities, progressive psychomotor development delay, severe hypotonia, and epilepsy. Standard karyotype is nearly always normal, but the isochromosome (12p) is present in a high percentage of skin fibroblasts. In this article, we report the case of 2 boys with Pallister-Killian syndrome having late-onset, drug-resistant epileptic spasms. Seizures have been reported in 40% of patients with Pallister-Killian syndrome but are poorly described. Epileptic spasms are not unusual in patients with brain malformations, chromosomal aberrations, and genetic syndromes, but epileptic spasms could be easily mistaken for behavioral manifestations. A better electroclinical characterization of epileptic seizures in Pallister-Killian syndrome using appropriate polygraphic tests (video-electroencephalography, electromyography) may lead to an early diagnosis and specific treatment for this form of epileptic spasms caused by this rare syndrome.