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Introduction. Ehlers Danlos syndrome is a group of hereditary diseases of the connective tissue with a combined prevalence of 1 in 5,000 cases which have in common articular hyperlaxity and skin abnormalities. In some types, rapid diagnosis can mean saving the life of the patient. Case presentation. We will present the case of a two year old girl which was brought for genetic consult with the suspicion of Ehlers Danlos syndrome. The patient had joint and skin hyperextensibility, velvety skin with a tendency of bruising, congenital hip luxation with a failed surgical intervention, talus varus and severe motor development retardation. Genetic testing revealed the substitution c.1780C>T, p.(Arg594*) in the COL5A1 gene which leads to the apparition of a premature stop codon, the mutation being class 2 (potentially pathogenic). Conclusions. Up until now, this variant has been reported in the literature in only two patients, ours being the third. All three cases correspond to the classic type Ehlers Danlos syndrome. [ABSTRACT FROM AUTHOR]

Objectives. Septo-optic dysplasia (SOD), also known as dec Morsier syndrome is a rare con-genital syndrome involving variable midline brain structures, characterized by visual impairment, pituitary deficiencies and specific brain abnormalities (especially midbrain malformations). The clinical phenotype is highly variable, from mild to extremely severe. The purpose of this paper is to present the electroencephalographic abnormalities in two clinical cases and correlate with the ones that have been described in the literature in order to find a specific trait of this syndrome. Methods and results. A 12-year-old girl was hospitalized in the pediatric neurology clinic for focal seizures, developmental delay and cerebral palsy. Clinical examination showed visual disturbances (nystagmus and oculomotor nerve palsy), unilateral pyramidal syndrome - left hemiparesis. Electroencephalography (EEG) revealedbilateral photosensitive epileptic form discharges, but asymmetrical, right more than left, with abnormal, slower background. MRI showed optic nerve hypoplasia and hypoplasia of the corpus callosum. The second case was also a girl, a 7-year-old who had only 2 focal right motor seizures with secondary generalization and developmental delay. Clinical examination showed visual impairment and bilateral nystagmus. The standard EEG evaluation didn't reveal any abnormalities, with normal background. Cerebral MRI showedmidline brain defects - agenesis of the septum pellucidum, agenesis of corpus callosum and optic nerve hypoplasia. Endocrine evaluation for pituitary function showed in the first case - increased thyroid-stimulating hormone and in the second case - decreased IGF1. Antiepileptic treatment was started in both cases, but seizures were refractory to treatment and persistent EEG abnormalitiesstill present in the first case, with good evolution of epilepsy in the second case. Conclusions. The epileptiform abnormalities associated to SOD are present only if there is an associated cortical malformation. [ABSTRACT FROM AUTHOR]

Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liver and skeletal system. The symptoms can consist in cystic renal disease and renal dystrophy, oculomotor apraxia, global developmental delay, hypotonia evolving into ataxia, skeletal and endocrine abnormalities, abnormal breathing patterns and congenital hepatic fibrosis, with the neurologic and ophthalmologic manifestations appearing early in life. The diagnostic hallmark is “the molar tooth sign”, a malformation of the brainstem and cerebellum easily identifiable using brain imaging techniques. As Joubert syndrome is a highly heterogeneous disease with a large type of phenotypes, it is oftentimes underdiagnosed. This article presents a case of Joubert syndrome type 17, a rare syndrome with many features overlapping orofaciodigital syndrome type VI. Adding to the rarity of this disease, our patient is homozygous and heterozygous for two pathogenic variants in C5orf42, with one located upstream of the other, thus manifesting the phenotype of a compound heterozygous in this gene. We believe that the presentation of this rare syndrome is useful to the pediatric practice by facilitating a fast diagnosis of these patients, which helps provide genetic counselling to the patients and their families. [ABSTRACT FROM AUTHOR]

Introduction. It is well know that progressive neuromuscular diseases affects muscles from entire body, including the ones responsible for breathing. Spinal Muscular Atrophy (SMA) is among the most common rare disease in children that affect respiratory function. Type I SMA is the most grave and lead to very weak intercostal muscles with a very soft and flexible chest during the first year of life, especially diaphragm, that is the primary muscle used to breath. Due to the respiratory muscle hypotonia, the patients can't breath/cough efficiently, thus not being able to eliminate the secretions that contribute supplementary to the respiratory insufficiency. Materials and Methods. We studied the evolution of 8 patients with SMA type I, that received in different moments of their lives the correct management of respiratory tract. Some of them had very early non-invasive ventilation during sleep, others received it only after they suffered respiratory infections. We observed the evolution of the chest perimeter during inspire every 4 months. We measured the pulsoximetry, respiratory frequency and CO2 exsufflation during the sleep in order to observe any improvements. Results. Only 2 of them had used early non-invasive ventilation, cough assist machine or a suction device for the secretions. 2 of the patients were tracheostomized, due to the lack of respiratory protocols among the intensive unit care. 1 of them died at the age of 14 months, even she had received 2 doses of Nusinersen treatment (anti-sense oligonucleotide that enables survival motor neuron protein). 1 patient received good respiratory management during a pneumonia episode and had no motor/respiratory regress after the acute disease. Conclusions. The respiratory management is very important and it is absolutely necessary in all patients with/without treatment. [ABSTRACT FROM AUTHOR]

1q44 microdeletion syndrome (1q44 monosomy) is a newly described genetic syndrome characterized by the haploinsufficiency of a 6 Mb locus on the long arm of chromosome 1. The main features are global developmental delay, seizures, hypotonia and craniofacial dysmorphism. With a prevalence below one in a million cases, this syndrome is very rare and, hence, often passes undiagnosed. We present the case of a one year old girl admitted to our hospital with global developmental delay and several congenital abnormalities suggesting a plurimalformative syndrome. Microarray analysis detected a 967 kb deletion in the 1q44 region as well as a a 530 kb microduplication in the 14q31.1q31.2 region, the latter having unknown clinical significance as it contains no currently known OMIM genes. The patient’s phenotype was in accordance to 1q44 microdeletion syndrome. Furthermore, after studying the 1q44 microdeletion syndrome cases reported so far in the literature, we have noticed that our patient presented previously undescribed features of this syndrome, namely prenatal hydronephrosis, bifid hallux and grey matter heterotopy. Based on the cerebral, renal and skeletal involvement in 1q44 microdeletion syndrome, we suspect these might be additional, previously unreported features of 1q44 microdeletion syndrome. [ABSTRACT FROM AUTHOR]

We present the case of a three-year-old girl with normal family history who was admitted to our hospital for medical recovery. The patient had microcephaly, pontocerebellar hypoplasia, slight facial dysmorphism, axial hypotonia, epileptic seizures, absent walking skills and severe speech delay. Genetic testing identified a heterozygous intronic variant in the CASK gene, namely CASK c.278 + 5G>A, which has never been reported in the medical literature or in other databases (gnomAD, ClinVar, HGMD). In mammals as well as more distant species, the G nucleotide is fully conserved at this position, suggesting it may not tolerate variation. In silico tools predict the substitution to be deleterious. Pathogenic mutations of these gene are responsible of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome, which overlaps completely with our patient’s phenotype. [ABSTRACT FROM AUTHOR]

Objectives. Neurofibromatosis type 1 (NF1) is a multisystem genetic neurocutaneous disease, with an autosomal dominant inheritance, affecting in a various degree the skin, the bones and also the nervous system. The neurological manifestation of this condition are due to peripheral nerves and also to associated brain lesions. Epilepsy can be one of the symptoms within NF1, with a double prevalence compared to the general population. The connection between seizures and neurofibromatosis type 1 is a clinically observable reality. Methods. This paper is a retrospective observational study over a period of 4 years of children admitted to pediatric neurology clinic with a diagnosis of NF1. Clinical (neurological symptoms, such as seizures, their onset, psychiatric and cognitive profile) and laboratory data (routine electroencephalography, brain imaging exams) were analyze in order to find a cause-effect relation of this association and also the evolution predictive factors. Results. There were evaluated 67 children with a diagnose of NF1 according to existing diagnostic criteria (1), and the association between epilepsy and neurofibromatosis type 1 has been reported in 4 patients, 2 boys and 2 girls. The onset of seizures had an average age of 36 months. 2 patients had drug resistant focal seizures associated with moderate and severe mental retardation. Cerebral magnetic resonance imaging (MRI), showed typical hiperintense lesions for this neurocutaneous syndrome only in 50% of cases. Conclusions. The article will present clinical and laboratory correlations between the association of seizures and neurofibromatosis in these 4 children, with reference to data published in the literature in this area. [ABSTRACT FROM AUTHOR]