Longitudinal Course of Cognitive, Adaptive, and Behavioral Characteristics in Costello Syndrome
cognitive; Genetics & Heredity; phenotype; features; functioning; HRAS; longitudinal assessment; MAP kinase pathway; p.G12A; p.G12S; p.G13C; p.T581; behavioral; tone and motor; costello syndrome; trajectory; characteristics; disability
Costello syndrome is a rare rasopathy caused by germline mutations in the oncogene HRAS resulting in increased signal transduction through the Ras/mitogen-activated protein kinase pathway. In contrast to the more common rasopathies, such as neurofibromatosis type 1 and Noonan syndrome, limited information is available on standardized cognitive testing in this cohort. Past research indicated a mean average IQ in the mild mental retardation range, with strengths in fluid reasoning (FR) and weakness in expressive language, as well as static skills over time. Here we report on standardized IQ and adaptive functioning in 18 individuals with Costello syndrome, nine males and nine females, and longitudinal development for 11 who had previous testing. The overall IQ, ranging from severe mental retardation to the average range, with a mean in the mildly mentally retarded range, was again found to be stable, but an interesting pattern in the development of nonverbal FR was identified. Participants showed an improvement in nonverbal FR, followed by stable skills thereafter, suggesting a "late bloomer" effect in late childhood/early adolescence. Overall adaptive functioning fell into the range of Intellectual Disability for 70% of subjects, with Socialization as a relative strength and Daily Living Skills an area of relative difficulty. Interestingly, females were found to be higher functioning than males in all domains, including Communication, Daily Living Skills and Socialization. Caregivers reported significantly more behavioral concerns in males, including internalizing, externalizing, and other maladaptive behaviors. In contrast, no gender differences were found in cognitive or visuomotor functioning. (C) 2009 Wiley-Liss, Inc.
Axelrad M E; Schwartz D D; Fehlis J E; Hopkins E; Stabley D L; Sol-Church K; Gripp K W
American Journal of Medical Genetics Part A
2009
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/ajmg.a.33126" target="_blank" rel="noreferrer noopener">10.1002/ajmg.a.33126</a>
Orthopedic manifestations and implications for individuals with Costello syndrome
tone and motor problems; Costello syndrome; trajectory; characteristics; orthopedic manifestations
Costello syndrome is a rare genetic condition caused by heterozygous alterations in HRAS and characterized by multi-system abnormalities. Individuals with Costello syndrome usually present with severe feeding difficulties in infancy, short stature, coarse facial features, increased tumor risks, cardiac and neurological complications, intellectual disability and orthopedic complications. This study further defines the orthopedic manifestations affecting individuals with Costello syndrome. We studied 43 participants and performed medical records review, clinical examinations and orthopedic inquiry forms. In 23 participants, hip and or spinal imaging assessments were completed. Serial radiographs were analyzed when available. A total of 25 orthopedic manifestations were identified. Ten manifestations were seen in the majority of the participants: hypotonia (87%), ligamentous laxity (85%), scoliosis (63%), kyphosis (58%), characteristic hand deformities (85%), ulnar deviation of the wrist (63%), elbow (55%) and shoulder contractures (65%), tight Achilles tendon (73%), and pes planus (53%). Other characteristics of special note were hip dysplasia (45%), foot deformities requiring surgical intervention (38%) and osteopenia/osteoporosis (47%). We also studied the development of the hips and spine. Uni- or bilateral hip dysplasia was congenital in some, while it developed throughout childhood in others. Spinal involvement included scoliosis, kyphosis, lordosis, and curvature reversal (thoracic lordosis and lumbar kyphosis). Based on these findings, we recommend routine referral to an orthopedic surgeon as well as instituting screening protocols for hips and spine for individuals with Costello syndrome.Copyright © 2013 Wiley Periodicals, Inc.
Detweiler S; Thacker M M; Hopkins E; Conway L; Gripp K W
American Journal of Medical Genetics Part A
2013
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/ajmg.a.36047" target="_blank" rel="noreferrer noopener">10.1002/ajmg.a.36047</a>