De novo 13q12.3-q14.11 deletion involvingBRCA2gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A-T like phenotype

2012 ◽  
Vol 158A (10) ◽  
pp. 2571-2576 ◽  
Author(s):  
Emilia Cirillo ◽  
Rosa Romano ◽  
Alfonso Romano ◽  
Giuliana Giardino ◽  
Anne Durandy ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Cerebellar Hypoplasia

scholarly journals De Novo Variants in WDR37 Are Associated with Epilepsy, Colobomas, Dysmorphism, Developmental Delay, Intellectual Disability, and Cerebellar Hypoplasia

2019 ◽  
Vol 105 (2) ◽  
pp. 413-424 ◽  
Author(s):  
Oguz Kanca ◽  
Jonathan C. Andrews ◽  
Pei-Tseng Lee ◽  
Chirag Patel ◽  
Stephen R. Braddock ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Cerebellar Hypoplasia

WED 201 A novel KIF1A mutation causing a neurodevelopmental disorder

2018 ◽  
Vol 89 (10) ◽  
pp. A29.3-A29
Author(s):  
Day Jacob ◽  
Turnpenny Peter ◽  
Gutowski Nick
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Novel Mutation ◽  
Hormone Replacement ◽  
Neurodevelopmental Disorder ◽  
Axonal Neuropathy ◽  
Periodic Limb Movements ◽  
Pituitary Hormone ◽  
Cerebellar Hypoplasia ◽  
Spastic Paraplegia

The KIF1A gene encodes a protein in the kinesin-3 family which drives movement along microtubules and is important for transport of synaptic vesicles. Biallelic mutations have been identified in autosomal recessive hereditary spastic paraplegia (HSP30) and hereditary sensory and autonomic neuropathy type 1A. More recently dominant heterozygous mutations have been found in people with a more severe phenotype that includes developmental delay, spastic paraplegia, neuropathy, optic nerve hypoplasia and progressive cerebellar hypoplasia.We report a female, now 22 years old, who has severe developmental delay, septo-optic dysplasia (requiring growth hormone and hydrocortisone replacement), sensorimotor axonal neuropathy, optic atrophy (now registered blind), non-progressive cerebellar hypoplasia, periodic limb movements and upper limb spasticity. She is extremely sensitive to gabapentin. A de novoKIF1A variant, c.814A>G, was identified. This is a novel missense variant (p.N272D) in the kinesin-motor domain.This case shows a phenotype consistent with previously described heterozygous KIF1A mutations and we believe represents a unifying diagnosis for her neurological disabilities. No previous cases describe non-progressive cerebellar hypoplasia nor septo-optic dysplasia requiring pituitary hormone replacement. This novel mutation therefore expands the phenotype associated with KIF1A mutations. We hypothesize that her sensitivity to gabapentin may be due to the KIF1A mutation.

scholarly journals De Novo Variants in WDR37 Are Associated with Epilepsy, Colobomas, Dysmorphism, Developmental Delay, Intellectual Disability, and Cerebellar Hypoplasia

2019 ◽  
Vol 105 (3) ◽  
pp. 672-674 ◽  
Author(s):  
Oguz Kanca ◽  
Jonathan C. Andrews ◽  
Pei-Tseng Lee ◽  
Chirag Patel ◽  
Stephen R. Braddock ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Cerebellar Hypoplasia

scholarly journals Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Gregorio Serra ◽  
Luigi Memo ◽  
Vincenzo Antona ◽  
Giovanni Corsello ◽  
Valentina Favero ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Variable Degree ◽  
Jacobsen Syndrome ◽  
Contiguous Gene ◽  
Clinical Consequences ◽  
11Q Deletion

Abstract Introduction In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified. Patients’ presentation We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, and pancytopenia of variable degree. Array comparative genomic hybridization (aCGH) identified a terminal deletion at 11q24.1-q25 of 12.5 Mb and 11 Mb, in Patient 1 and 2, respectively. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletion for Patient 1; parents of Patient 2 refused further genetic investigations. Conclusions Present newborns show the full phenotype of JBS including thrombocytopenia, according to their wide 11q deletion size. Bleeding was particularly severe in one of them, leading to a cerebral hemorrhage. Our report highlights the relevance of early diagnosis, genetic counselling and careful management and follow-up of JBS patients, which may avoid severe clinical consequences and lower the mortality risk. It may provide further insights and a better characterization of JBS, suggesting new elements of the genotype-phenotype correlations.

scholarly journals The de novo CACNA1A pathogenic variant Y1384C associated with hemiplegic migraine, early onset cerebellar atrophy and developmental delay leads to a loss of Cav2.1 channel function

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
A. Micheil Innes ◽  
Gerald W. Zamponi
Keyword(s):  
Developmental Delay ◽  
Early Onset ◽  
Structural Damage ◽  
De Novo ◽  
Splice Variants ◽  
Cerebellar Atrophy ◽  
Familial Hemiplegic Migraine ◽  
Significant Loss ◽  
Loss Of Function ◽  
Hemiplegic Migraine

AbstractCACNA1A pathogenic variants have been linked to several neurological disorders including familial hemiplegic migraine and cerebellar conditions. More recently, de novo variants have been associated with severe early onset developmental encephalopathies. CACNA1A is highly expressed in the central nervous system and encodes the pore-forming CaVα1 subunit of P/Q-type (Cav2.1) calcium channels. We have previously identified a patient with a de novo missense mutation in CACNA1A (p.Y1384C), characterized by hemiplegic migraine, cerebellar atrophy and developmental delay. The mutation is located at the transmembrane S5 segment of the third domain. Functional analysis in two predominant splice variants of the neuronal Cav2.1 channel showed a significant loss of function in current density and changes in gating properties. Moreover, Y1384 variants exhibit differential splice variant-specific effects on recovery from inactivation. Finally, structural analysis revealed structural damage caused by the tyrosine substitution and changes in electrostatic potentials.

scholarly journals MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

2021 ◽  
Author(s):  
Linyan Meng ◽  
Pirjo Isohanni ◽  
Yunru Shao ◽  
Brett H. Graham ◽  
Scott E. Hickey ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Cerebellar Hypoplasia

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias

2020 ◽  
Author(s):  
Margherita Nosadini ◽  
Gianluca D'Onofrio ◽  
Maria Federica Pelizza ◽  
Concetta Luisi ◽  
Davide Padrin ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Developmental Delay ◽  
De Novo ◽  
Brain Magnetic Resonance Imaging ◽  
Neurological Impairment ◽  
De Novo Mutation ◽  
Oligoclonal Bands ◽  
Emotional Stimuli ◽  
Childhood Onset ◽  
Ataxic Gait

Abstract Background Mutations in the adenylate cyclase 5 (ADCY5) gene are associated with childhood-onset paroxysmal dyskinesia. Methods We report a new video-documented case of pediatric ADCY5-related dyskinesia with de novo ADCY5 mutation. Results A boy born to nonconsanguineous parents after an uneventful pregnancy had developmental delay and hypotonia. At the age of 7 months, he presented with paroxysmal jerky–choreic–dystonic involuntary movements in wakefulness involving limbs, trunk, and face, exacerbated by emotional stimuli. These episodes gradually worsened in duration and frequency: at the age of 2.5 years, they occurred up to six times per day, and appeared also during sleep in prolonged bouts; the boy also had basal choreoathetoid–dystonic movements, hyperactivity, paraparetic–ataxic gait, generalized hypotonia with brisk tendon reflexes, drooling, and language delay with intellectual disability. Brain magnetic resonance imaging, electroencephalogram, electromyogram, eye review, metabolic investigations, oligoclonal bands, and autoantibodies were normal. Extensive genetic testing had not let to a diagnosis, until a heterozygous de novo mutation c.1252C > T (p.Arg418Trp) was identified in the ADCY5 gene. Clonazepam had partial effectiveness. The boy walked at the age of 3.5 years. At the age of 5 years, the paroxysmal movement disorder has slightly improved. Conclusion ADCY5 mutations should be considered among the differential diagnoses of early-onset paroxysmal choreic–athetosic–myoclonic–dystonic movement disorder involving limbs, trunk, and face, in patients with global neurological impairment with hypotonia and developmental delay. Facial dyskinesias and exacerbation by drowsiness/sleep and emotional stimuli are important clues that may allow a timely recognition of the disorder and avoidance of unnecessary diagnostic investigations.

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

2021 ◽  
Author(s):  
Evan Jiang ◽  
Mark P. Fitzgerald ◽  
Katherine L. Helbig ◽  
Ethan M. Goldberg
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Synapse Formation ◽  
De Novo ◽  
Interleukin 1 ◽  
Autism Spectrum ◽  
Neurological Dysfunction ◽  
Behavioral Disorder ◽  
Clinical Genetic ◽  
Severe Intellectual Disability

AbstractInterleukin-1 receptor accessory protein-like 1 (IL1RAPL1) encodes a protein that is highly expressed in neurons and has been shown to regulate neurite outgrowth as well as synapse formation and synaptic transmission. Clinically, mutations in or deletions of IL1RAPL1 have been associated with a spectrum of neurological dysfunction including autism spectrum disorder and nonsyndromic X-linked developmental delay/intellectual disability of varying severity. Nearly all reported cases are in males; in the few reported cases involving females, the clinical presentation was mild or the deletion was identified in phenotypically normal carriers in accordance with X-linked inheritance. Using genome-wide microarray analysis, we identified a novel de novo 373 kb interstitial deletion of the X chromosome (Xp21.1-p21.2) that includes exons 4 to 6 of the IL1RAPL1 gene in an 8-year-old girl with severe intellectual disability and behavioral disorder with a history of developmental regression. Overnight continuous video electroencephalography revealed electrical status epilepticus in sleep (ESES). This case expands the clinical genetic spectrum of IL1RAPL1-related neurodevelopmental disorders and highlights a new genetic association of ESES.

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