Attention deficit hyperactivity disorder (ADHD) in phenotypically similar neurogenetic conditions: Turner syndrome and the RASopathies

Green, Tamar; Naylor, Paige E.; Davies, William

doi:10.1186/s11689-017-9205-x

Cited by 25 publications

(27 citation statements)

References 120 publications

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“…Research among children diagnosed with NF1 and NS has consistently identified difficulties related to attention problems and social deficits (Adviento et al, ; Green et al, ; Noll et al, ; Pierpont et al, ). Results of the current study emphasize the need for further examination of internalizing symptoms among individuals with RASopathies, especially in children with a comorbid ADHD diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

McNeill

Hudock

Foy

et al. 2019

American J of Med Genetics Pt A

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While neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are clinically distinct genetic syndromes, they have overlapping features because they are caused by pathogenic variants in genes encoding molecules within the Ras-mitogen-activated protein kinase signaling pathway. Increased risk for emotional and behavioral challenges has been reported in both children and adults with these syndromes. The current study examined parent-report and self-report measures of emotional functioning among children with NF1 and NS as compared to their unaffected siblings. Parents and children with NS (n = 39), NF1 (n = 39), and their siblings without a genetic condition (n = 32) completed well-validated clinical symptom rating scales. Results from parent questionnaires indicated greater symptomatology on scales measuring internalizing behaviors and symptoms of attention deficit hyperactivity disorder (ADHD) in both syndrome groups as compared with unaffected children. Frequency and severity of emotional and behavioral symptoms were remarkably similar across the two clinical groups. Symptoms of depression and anxiety were higher in children who were also rated as meeting symptom criteria for ADHD. While self-report ratings by children generally correlated with parent ratings, symptom severity was less pronounced. Among unaffected siblings, parent ratings indicated higher than expected levels of anxiety. Study findings may assist with guiding family-based interventions to address emotional challenges. K E Y W O R D Sanxiety, depression, emotional function, neurofibromatosis type 1, Noonan syndrome, RASopathies

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Section: Discussionmentioning

confidence: 99%

Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

McNeill

Hudock

Foy

et al. 2019

American J of Med Genetics Pt A

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“…Attention deficit hyperactivity disorder (ADHD) is associated with a significant proportion of RASopathy cases (Adviento et al, 2014; Garg et al, 2013; Green et al, 2017; Pierpont et al, 2018; Walsh et al, 2013). Altered prefrontal cortex (PFC) function has been implicated in ADHD (Gabay et al, 2018), and has been shown to contribute to cognitive deficits in a mouse model of Fragile X Syndrome (Krueger et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Hyperactive MEK1 signaling in cortical GABAergic neurons causes embryonic parvalbumin-neuron death and defects in behavioral inhibition

Holter

Hewitt

Nishimura

et al. 2019

Preprint

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1Abnormal ERK/MAPK pathway activity is an important contributor to the neuropathogenesis of 2 many disorders including Fragile X, Rett, 16p11.2 Syndromes, and the RASopathies. Individuals with these 3 syndromes often present with intellectual disability, ADHD, autism, and epilepsy. However, the 4 pathological mechanisms that underly these deficits are not fully understood. Here, we examined whether 5 hyperactivation of MEK1 signaling modifies the development of GABAergic cortical interneurons (CINs), 6 a heterogeneous population of inhibitory neurons necessary for cortical function. We show that 7 GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling 8 in a subpopulation of immature neurons in the embryonic subpallium. Adult mutants displayed a significant 9 loss of mature parvalbumin-expressing (PV) CINs, but not somatostatin-expressing CINs, during postnatal 10 development and a modest reduction in perisomatic inhibitory synapse formation on excitatory neurons. 11Surviving mutant PV-CINs maintained a typical fast-spiking phenotype and minor differences in intrinsic 12 electrophysiological properties. These changes coincided with an increased risk of seizure-like phenotypes. 13 In contrast to other mouse models of PV-CIN loss, we discovered a robust increase in the accumulation of 14 perineuronal nets, an extracellular structure thought to restrict plasticity in the developing brain. Indeed, we 15 found that mutants exhibit a significant impairment in the acquisition of a behavioral test that relies on 16 behavioral response inhibition, a process linked to ADHD-like phenotypes. Overall, our data suggests PV-17

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“…Examples include neurofibromatosis type 1 (NF1), Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, and LEOPARD syndrome (47). Patient phenotypes of the various syndromes are diverse, but share some overlapping features, including cardiac and vascular abnormalities, developmental delay, neurodevelopmental phenotypes (autism and ADHD) and predisposition to cancer (48)(49)(50). Intriguingly, all individuals haploinsufficient for CIC have developmental delay and neurodevelopmental phenotypes, and some individuals have cardiac and vascular abnormalities (5).…”

Section: Discussionmentioning

confidence: 99%

Loss of Capicua alters early T cell development and predisposes mice to T cell lymphoblastic leukemia/lymphoma

Tan

Brunetti

Rousseaux

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Capicua (CIC) regulates a transcriptional network downstream of the RAS/MAPK signaling cascade. In , CIC is important for many developmental processes, including embryonic patterning and specification of wing veins. In humans, CIC has been implicated in neurological diseases, including spinocerebellar ataxia type 1 (SCA1) and a neurodevelopmental syndrome. Additionally, we and others have reported mutations in in several cancers. However, whether CIC is a tumor suppressor remains to be formally tested. In this study, we found that deletion of in adult mice causes T cell acute lymphoblastic leukemia/lymphoma (T-ALL). Using hematopoietic-specific deletion and bone marrow transplantation studies, we show that loss of from hematopoietic cells is sufficient to drive T-ALL. -null tumors show up-regulation of the KRAS pathway as well as activation of the NOTCH1 and MYC transcriptional programs. In sum, we demonstrate that loss of CIC causes T-ALL, establishing it as a tumor suppressor for lymphoid malignancies. Moreover, we show that mouse models lacking CIC in the hematopoietic system are robust models for studying the role of RAS signaling as well as NOTCH1 and MYC transcriptional programs in T-ALL.

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Attention deficit hyperactivity disorder (ADHD) in phenotypically similar neurogenetic conditions: Turner syndrome and the RASopathies

Cited by 25 publications

References 120 publications

Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

Hyperactive MEK1 signaling in cortical GABAergic neurons causes embryonic parvalbumin-neuron death and defects in behavioral inhibition

Loss of Capicua alters early T cell development and predisposes mice to T cell lymphoblastic leukemia/lymphoma

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