A case of postapoplectic hemichorea with sensory and autonomic disorders

Th. Dosuzkov and Ed. Bena (Revue v. Neurologii i psychiatrii, 1928, nos. 3 and 4). Choreic contractions were noted in the right half of the face and right limbs. These contractions decreased under the influence of volitional tension, increased with distraction of attention, with emotions and unpleasant peripheral sensations. On the right side, the patient had friendly motions of the imitation type, muscle hypotonia, absence of setting reflexes, the presence of tactile hypeesthesia and decreased vibration sensitivity on the right side, miosis and increased sweating on the right.

Potocki-Lupski Syndrome Dup17p11.2 in a Girl with Hypotonia and Early Behavioural Disturbances

Potocki-Lupski syndrome (PTLS) is a contiguous gene syndrome caused by duplication of chromosome 17p11.2. PTLS is characterized by hypotonia, failure to thrive, congenital anomalies (particularly of the cardiovascular system), intellectual disability, and behavioural disturbances. The patient was a full-term baby girl, 2,750 grams at birth, delivered via an uncomplicated vaginal delivery with pronounced hypotonia at birth. Nevertheless, there was failure to thrive (weight 7.6 kg; 2.8 SD). Micrognathia, epicanthal skin folds, and megalocornea were noticeable. There was a harsh continuous systolic murmur, and the ultrasound of the heart revealed a persistent arteriosus duct which was surgically closed. At the age of 18 months, the girl could not sit without support, and she could not utter simple words. The girl is often moody, angry, and aggressive. She is hyperactive and unable to establish contacts with family members. A 17p12-p11.2 microduplication was identified via MLPA. Muscle hypotonia, congenital heart malformation, failure to thrive, developmental delay, behavioural disturbances (or autism spectrum disorder), and intellectual disability are early signs of PTLS. The presence of PTLS was proven by an MLPA analysis.

Usefulness of Trichoscopy over Hair Light Microscopy in Menkes Disease

Menkes disease (MD) is a rare X-linked recessive neurodegenerative disorder caused by mutations in the <i>ATP7A</i> gene, with a high mortality rate within the first 3 years of life. It typically affects males and is characterized by impaired copper distribution and malfunction of several copper-dependent enzymes. Patients develop progressive muscle hypotonia associated with neurological damage and hair shaft dysplasia – particularly pili torti. Pili torti is usually very subtle in the first 3 months of life and gradually increases during the first year. Light microscopy examination in search for pili torti requires the observation of more than 50 hair shafts. In contrast, trichoscopy with a hand-held dermatoscope allows to easily identify the hair shaft defect. We report a case of a Hispanic male infant with MD in whom we show that trichoscopy is superior to hair light microscopy in revealing pili torti.

Effects of Resistance Training in Muscle Mass and Markers of Muscle Damage in Adults with Down Syndrome

Recent studies have emphasized that regular exercise should be encouraged as a key part of care and support for people with Down syndrome (DS). However, muscle hypotonia has traditionally been considered a major barrier to resistance training (RT) in people with DS. The main objective of this study was to analyze the impact of circuit RT on markers of muscle damage. The secondary objective was to assess the influence of a RT program on body composition and work task performance. Thirty-six men with DS were recruited and randomly assigned to perform a circuit RT program with six stations 3 days/week for 12 weeks (n = 18) or to a control group (n = 18). Body composition was assessed by bioelectrical impedance analysis. Serum markers of muscle damage (creatine kinase, myoglobin, and lactate dehydrogenase) were determined at baseline and at the end of training weeks 1, 6, and 12. Work task performance was assessed using the weighted pail-carry test. RT did not induce significant changes in markers of muscle damage during the intervention. Furthermore, muscle mass and work task performance were significantly improved in the exercise group. These findings suggest that circuit RT can be used safely to increase muscle mass and work task performance in young adults with DS. Muscle hypotonia should not be considered a major barrier to exercise in people with DS, provided that qualified staff design and supervise all training sessions.

Mutation in ZDHHC15 Leads to Hypotonic Cerebral Palsy, Autism, Epilepsy, and Intellectual Disability

ObjectiveTo determine whether mutations reported for ZDHHC15 can cause mixed neurodevelopmental disorders, we performed both functional studies on variant pathogenicity and ZDHHC15 function in animal models.MethodsWe examined protein function of 4 identified variants in ZDHHC15 in a yeast complementation assay and locomotor defects of loss-of-function genotypes in a Drosophila model.ResultsAlthough we assessed multiple patient variants, only 1 (p.H158R) affected protein function. We report a patient with a diagnosis of hypotonic cerebral palsy, autism, epilepsy, and intellectual disability associated with this bona fide damaging X-linked variant. Features include tall forehead with mild brachycephaly, down-slanting palpebral fissures, large ears, long face, facial muscle hypotonia, high-arched palate with dental crowding, and arachnodactyly. The patient had mild diminished cerebral volume, with left-sided T2/FLAIR hyperintense periatrial ovoid lesion. We found that loss-of-function mutations in orthologs of this gene cause flight and coordinated movement defects in Drosophila.ConclusionsOur findings support a functional expansion of this gene to a role in motor dysfunction. Although ZDHHC15 mutations represent a rare cause of neurodevelopmental disability, candidate variants need to be carefully assessed before pathogenicity can be determined.

Pervasive developmental disorders with a complex structure (epileptic seizures, catatonic, hallucinatory and manic symptoms, delirious episodes during life).

Observation of two patients with Phelan-McDermid syndrome (22q13.3 microdeletions of the SHANK3 gene) within 10—12 years allowed us to describe the clinical pathomorphism of psychotic episodes with violation of consciousness and catatonic symptoms in adolescence with autism spectrum disorders (ASD). The described phenotypes were characterized by intellectual disability, general speech underdevelopment, muscle hypotonia and developmental dyspraxia. Their causal relationships with epileptic encephalopathy, schizophrenia, bipolar and hyperkinetic disorders have been analyzed. The therapeutic efficacy of combination therapy with aripiprazole and benzodiazepines (clonazepam/diazepam) allowed qualifying psychotic episodes as pediatric delirium. The significant clinical efficacy of lithium and lamotrigine in the described patients was consistent with the hypothesis that microdeletion of the SHANK3 gene may be associated with bipolar disorder. Treatment of acute psychotic disorders with lithium salt was effective in both patients but had limitations due to poor tolerance in the long-term use. The combination of lithium and lamotrigine may be recommended for the treatment of polymorbid mental disorders in patients with SHANK3 encephalopathies. If lithium salts are poorly tolerated, a combination of lamotrigine and aripiprazole may be used.

Oral motor problems – what you may recommend your little patients

Babies and infants getting osteophatic therapies may show oral functional disorders, such as insufficient sucking, problems with mashed, semisolid or solid food, up to choking (dysphagia); open mouth, tongue protrusion, drooling. This article highlights medical contexts (muscle hypotonia, hypertonia/spasticity) and explains indications to a more specific therapy: such as the Castillo Morales®- Conzept .

De novo variant in the MAPK8IP3 gene in the differential diagnosis of global development delay. Case report.

Context: The global development delay has a high prevalence and heterogeneity in the world population. With the advancement of technology and detection of pathogenic variants detected by sequencing the exome, genes related to global developmental delay could be identified and collaborate for further clinical clarification. Among the studied genes, the MAPK8IP3 gene, became an attractive candidate due to its performance in neuronal axonal transport in vertebrates and invertebrates. This case report was approved by the Ethics Committee of Universidade Metropolitana de Santos. Case Report: The present case refers to a 6-year-old male patient presenting with a clinical picture of global developmental delay without bodily dysmorphia. Cerebellar ataxia, muscle hypotonia and intellectual impairment are important clinical impairments. Skull MRI and complementary exams were normal. The genetic study showed a new and heterozygous pathogenic variant in the MAPK8IP3 gene. Conclusions: Symptomatic treatment with multiprofessional rehabilitation was instituted with partial improvement of symptoms.

b3galt6 Knock-Out Zebrafish Recapitulate β3GalT6-Deficiency Disorders in Human and Reveal a Trisaccharide Proteoglycan Linkage Region

Proteoglycans are structurally and functionally diverse biomacromolecules found abundantly on cell membranes and in the extracellular matrix. They consist of a core protein linked to glycosaminoglycan chains via a tetrasaccharide linkage region. Here, we show that CRISPR/Cas9-mediated b3galt6 knock-out zebrafish, lacking galactosyltransferase II, which adds the third sugar in the linkage region, largely recapitulate the phenotypic abnormalities seen in human β3GalT6-deficiency disorders. These comprise craniofacial dysmorphism, generalized skeletal dysplasia, skin involvement and indications for muscle hypotonia. In-depth TEM analysis revealed disturbed collagen fibril organization as the most consistent ultrastructural characteristic throughout different affected tissues. Strikingly, despite a strong reduction in glycosaminoglycan content, as demonstrated by anion-exchange HPLC, subsequent LC-MS/MS analysis revealed a small amount of proteoglycans containing a unique linkage region consisting of only three sugars. This implies that formation of glycosaminoglycans with an immature linkage region is possible in a pathogenic context. Our study, therefore unveils a novel rescue mechanism for proteoglycan production in the absence of galactosyltransferase II, hereby opening new avenues for therapeutic intervention.