scholarly journals Case Report: Bilateral Epiphysiodesis Due to Extreme Tall Stature in a Girl With a De Novo DNMT3A Variant Associated With Tatton-Brown-Rahman Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Otto Lennartsson ◽  
Maria Lodefalk ◽  
Henrik Wehtje ◽  
Eva-Lena Stattin ◽  
Lars Sävendahl ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Clinical Case ◽  
Distal Femur ◽  
De Novo ◽  
Bone Age ◽  
Autism Spectrum ◽  
Tall Stature ◽  
Leg Length ◽  
Early Puberty

ObjectiveTo present a rare clinical case of a patient with Tatton-Brown-Rahman syndrome and the outcome of tall stature management with bilateral epiphysiodesis surgery at the distal femur and proximal ends of tibia and fibula.Study DesignClinical case report.ResultsThis is a 20-year-old female with a history of proportional tall stature, developmental psychomotor and language delay with autism spectrum behavior and distinctive facial features. At 12 years and 2 months of age she was in early puberty and 172.5 cm tall (+ 2.8 SDS) and growing approximately 2 SDS above midparental target height of 173 cm (+ 0.9 SDS). A bone age assessment predicted an adult height of 187.1 cm (+3.4 SDS). To prevent extreme tall stature, bilateral epiphysiodesis surgery was performed at the distal femur and proximal ends of tibia and fibula at the age of 12 years and 9 months. After the surgery her height increased by 12.6 cm to 187.4 cm of which approximately 10.9 cm occurred in the spine whereas leg length increased by only 1.7 cm resulting in a modest increase of sitting height index from 50% (-1 SDS) to 53% (+ 0.5 SDS). Genetic evaluation for tall stature and intellectual disability identified a de novo nonsense variant in the DNMT3A gene previously associated with Tatton-Brown-Rahman syndrome.ConclusionTatton-Brown-Rahman syndrome should be considered in children with extreme tall stature and intellectual disability. Percutaneous epiphysiodesis surgery to mitigate extreme tall stature may be considered.

scholarly journals Epiphysiodesis for the treatment of tall stature and leg length discrepancy

2021 ◽  
Author(s):  
Madeleine Willegger ◽  
Markus Schreiner ◽  
Alexander Kolb ◽  
Reinhard Windhager ◽  
Catharina Chiari
Keyword(s):  
Surgical Planning ◽  
Multidisciplinary Approach ◽  
Treatment Options ◽  
Bone Age ◽  
Leg Length Discrepancy ◽  
Tall Stature ◽  
Complication Rates ◽  
Leg Length ◽  
Growth Prediction ◽  
Length Discrepancy

SummaryPainful orthopedic conditions associated with extreme tall stature and leg length discrepancy (LLD) include back pain and adopting bad posture. After failure of conservative treatment options, blocking of the growth plates (epiphysiodesis) around the knee emerged as gold standard in patients with tall stature and LLD in the growing skeleton. Surgical planning includes growth prediction and evaluation of bone age. Since growth prediction is associated with a certain potential error, adequate planning and timing of epiphysiodesis are the key for success of the treatment. LLD corrections up to 5 cm can be achieved, and predicted extreme tall stature can be limited. Percutaneous epiphysiodesis techniques are minimally invasive, safe and efficient methods with low complication rates. In general, a multidisciplinary approach should be pursued when treating children and adolescents with tall stature.

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.

scholarly journals Pitt–Hopkins syndrome with electrical stat us epileptic us in slo w-wave sleep: a case report

2019 ◽  
Vol 14 (2) ◽  
pp. 42-48
Author(s):  
N. G. Lyukshina
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Status Epilepticus ◽  
Neuronal Differentiation ◽  
Clinical Case ◽  
Genetic Disorder ◽  
Facial Dysmorphism ◽  
Autistic Behavior ◽  
Rare Genetic Disorder ◽  
Molecular Variant

Pitt–Hoppkins syndrome is rare genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. The syndrome is characterized by specific facial dysmorphism, phychomotor delay, autistic behavior and intellectual disability. Other associated features include ealy-onset myopia, seizures, constipation and hyperventilation-apneic spells. We introduced a clinical case of the patient with molecularly confirmed TCF4 variant and previously undescribed combination with syndrome of the electrical status epilepticus during sleep.

A case of Luscan-Lumish syndrome: Possible involvement of enhanced GH signaling

2020 ◽  
Author(s):  
Kentaro Suda ◽  
Hidenori Fukuoka ◽  
Genzo Iguchi ◽  
Keitaro Kanie ◽  
Yasunori Fujita ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Novel Mutation ◽  
Body Height ◽  
Chiari I Malformation ◽  
Oral Glucose ◽  
Tall Stature ◽  
Sequencing Analysis ◽  
Serum Growth Hormone ◽  
Chiari I

Abstract Context Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear. Case description A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg/m 2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T>A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH. Conclusion This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.

scholarly journals A De Novo Mutation in DYRK1A Causes Syndromic Intellectual Disability: A Chinese Case Report

2019 ◽  
Vol 10 ◽  
Author(s):  
Fengchang Qiao ◽  
Binbin Shao ◽  
Chen Wang ◽  
Yan Wang ◽  
Ran Zhou ◽  
...  
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
De Novo ◽  
De Novo Mutation ◽  
Chinese Case

scholarly journals Pathogenic WDFY3 variants cause neurodevelopmental disorders and opposing effects on brain size

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2617-2630 ◽  
Author(s):  
Diana Le Duc ◽  
Cecilia Giulivi ◽  
Susan M Hiatt ◽  
Eleonora Napoli ◽  
Alexios Panoutsopoulos ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Wnt Pathway ◽  
De Novo ◽  
Autism Spectrum ◽  
Neural Progenitors ◽  
Scaffolding Protein ◽  
Published Data ◽  
Ph Domain ◽  
Human Phenotype ◽  
Neurodevelopmental Delay

Abstract The underpinnings of mild to moderate neurodevelopmental delay remain elusive, often leading to late diagnosis and interventions. Here, we present data on exome and genome sequencing as well as array analysis of 13 individuals that point to pathogenic, heterozygous, mostly de novo variants in WDFY3 (significant de novo enrichment P = 0.003) as a monogenic cause of mild and non-specific neurodevelopmental delay. Nine variants were protein-truncating and four missense. Overlapping symptoms included neurodevelopmental delay, intellectual disability, macrocephaly, and psychiatric disorders (autism spectrum disorders/attention deficit hyperactivity disorder). One proband presented with an opposing phenotype of microcephaly and the only missense-variant located in the PH-domain of WDFY3. Findings of this case are supported by previously published data, demonstrating that pathogenic PH-domain variants can lead to microcephaly via canonical Wnt-pathway upregulation. In a separate study, we reported that the autophagy scaffolding protein WDFY3 is required for cerebral cortical size regulation in mice, by controlling proper division of neural progenitors. Here, we show that proliferating cortical neural progenitors of human embryonic brains highly express WDFY3, further supporting a role for this molecule in the regulation of prenatal neurogenesis. We present data on Wnt-pathway dysregulation in Wdfy3-haploinsufficient mice, which display macrocephaly and deficits in motor coordination and associative learning, recapitulating the human phenotype. Consequently, we propose that in humans WDFY3 loss-of-function variants lead to macrocephaly via downregulation of the Wnt pathway. In summary, we present WDFY3 as a novel gene linked to mild to moderate neurodevelopmental delay and intellectual disability and conclude that variants putatively causing haploinsufficiency lead to macrocephaly, while an opposing pathomechanism due to variants in the PH-domain of WDFY3 leads to microcephaly.

scholarly journals A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability

2015 ◽  
Vol 24 (6) ◽  
pp. 838-843 ◽  
Author(s):  
Anne-Laure Mosca-Boidron ◽  
Lucie Gueneau ◽  
Guillaume Huguet ◽  
Alice Goldenberg ◽  
Céline Henry ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder

De Novo HECW2 Mutation Associated With Epilepsy, Developmental Decline, and Intellectual Disability: Case Report and Review of Literature

2018 ◽  
Vol 85 ◽  
pp. 76-78 ◽  
Author(s):  
Natalie L. Ullman ◽  
Constance L. Smith-Hicks ◽  
Sonal Desai ◽  
Carl E. Stafstrom
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
De Novo ◽  
Review Of Literature

scholarly journals De novo variants in SETD1B cause intellectual disability, autism spectrum disorder, and epilepsy with myoclonic absences

2019 ◽  
Vol 4 (3) ◽  
pp. 476-481 ◽  
Author(s):  
Takuya Hiraide ◽  
Ayako Hattori ◽  
Daisuke Ieda ◽  
Ikumi Hori ◽  
Shinji Saitoh ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder
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