TY - JOUR
T1 - PACS1-Neurodevelopmental disorder
T2 - clinical features and trial readiness
AU - Van Nuland, Abigail
AU - Reddy, Taruna
AU - Quassem, Farhad
AU - Vassalli, Jean Dominique
AU - Berg, Anne T.
N1 - Funding Information:
Supported by the Stanley Manne Children’s Research Institute and Ann & Robert H. Lurie Children’s Hospital of Chicago under the Precision Medicine Strategic Research Initiative and a grant from the Pediatric Epilepsy Research Foundation (PERF).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: PACS1-Neurodevelopmental Disorder (PACS1-NDD) is an ultra-rare condition due to a recurrent mutation in the PACS1 gene. Little systematically collected data exist about the functional abilities and neurodevelopmental morbidities in children with PACS1-NDD Methods: Parents of individuals with PACS1-NDD completed an on-line survey designed collaboratively by researchers, parents, and clinicians. Analyses focused on those with a confirmed R203W variant. Results: Of 35 individuals with confirmed variants, 18 (51%) were female. The median age was 8 years (interquartile range 4.5–15). Seventeen (49%) had a diagnosis of epilepsy. Twelve (40%, of 30 responding to the question) reported autism and (N = 11/30, 37%) reported features of autism. Most children walked independently (N = 29/32, 91%), had a pincer grasp (N = 23/32, 72%), could feed themselves independently (N = 15/32, 47%), and used speech (N = 23/32, 72%). Sixteen of twenty-nine (55%) had simple pre-academic skills. Neither epilepsy nor autism was associated with functional abilities or other clinical features (all P > 0.05). Conclusions: PACS1-NDD is a moderately-severe intellectual disability syndrome in which seizures occur but are not a defining or primary feature. Successful precision medicine clinical trials for this ultra-rare disorder must target important core features of this disorder and utilize assessment tools commensurate with the level of function in this clinical population.
AB - Background: PACS1-Neurodevelopmental Disorder (PACS1-NDD) is an ultra-rare condition due to a recurrent mutation in the PACS1 gene. Little systematically collected data exist about the functional abilities and neurodevelopmental morbidities in children with PACS1-NDD Methods: Parents of individuals with PACS1-NDD completed an on-line survey designed collaboratively by researchers, parents, and clinicians. Analyses focused on those with a confirmed R203W variant. Results: Of 35 individuals with confirmed variants, 18 (51%) were female. The median age was 8 years (interquartile range 4.5–15). Seventeen (49%) had a diagnosis of epilepsy. Twelve (40%, of 30 responding to the question) reported autism and (N = 11/30, 37%) reported features of autism. Most children walked independently (N = 29/32, 91%), had a pincer grasp (N = 23/32, 72%), could feed themselves independently (N = 15/32, 47%), and used speech (N = 23/32, 72%). Sixteen of twenty-nine (55%) had simple pre-academic skills. Neither epilepsy nor autism was associated with functional abilities or other clinical features (all P > 0.05). Conclusions: PACS1-NDD is a moderately-severe intellectual disability syndrome in which seizures occur but are not a defining or primary feature. Successful precision medicine clinical trials for this ultra-rare disorder must target important core features of this disorder and utilize assessment tools commensurate with the level of function in this clinical population.
KW - Autism
KW - Epilepsy
KW - Neurodevelopment
KW - PACS1
KW - Precision medicine
KW - Schuurs-Hoeijmakers syndrome
KW - Trial readiness
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U2 - 10.1186/s13023-021-02001-1
DO - 10.1186/s13023-021-02001-1
M3 - Article
C2 - 34517877
AN - SCOPUS:85114822765
VL - 16
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
IS - 1
M1 - 386
ER -