Costello syndrome and neurological abnormalities

Abstract

Costello syndrome is a rare but increasingly recognized syndrome of unknown etiology. Neurological abnormalities are not rare in this syndrome and consist of structural and electrophysiological disorders. Ventricular dilatation is observed in more than 40% of cases. Other reported cerebral anomalies are brain atrophy, Chiari malformation and syringomyelia. Although there is insufficient data to propose strict guidelines, it seams reasonnable to have a low threshold for neuroimaging, in general, and particularly when neurologic signs or symptoms are present. Screening including cerebral MRI and EEG should be proposed after a diagnosis of Costello syndrome. The frequency of testing in such children should be guided by neurological follow‐up. © 2003 Wiley‐Liss, Inc.

Costello syndrome with growth hormone deficiency and hypoglycemia: A new report and review of the endocrine associations

“…As Johnson et al [1998] note, many findings in CS point toward a metabolic basis for the condition, and it is interesting to speculate whether this metabolic abnormality may originate in the hypothalamic-pituitary axis. This hypothesis is supported by the reports of combined GH and cortisol deficiency in the patient of Yetkin et al [1998] (and strongly suspected in our patient), combined GH and thyroid hormone deficiency in the patient of Gripp et al [2000], the other reported cases of isolated GH deficiency [Okamoto et al, 1994;Schimke et al, 1996;Legault and Gagnon, 2002;Delrue et al, 2003]], and mention of elevated prolactin levels in one patient with CS [Johnson et al, 1998]. Lin et al [2002] speculated that GH therapy in CS patients may cause the progression of existing cardiac hypertrophy, or initiate hypertrophy in patients with an apparently normal myocardium.…”

“…It has also been noted that patients with CS are at increased risk for the development of tumors [DeBaun, 2002;Gripp et al, 2002]. Further, a few reports describe endocrine abnormalities in some patients with CS, specifically of growth hormone (GH) [Okamoto et al, 1994;Schimke et al, 1996;Yetkin et al, 1998;Legault and Gagnon, 2002;Delrue et al, 2003] and glucose metabolism [Di Rocco et al, 1993;Johnson et al, 1998;Yetkin et al, 1998;Szalai et al, 1999;Gripp et al, 2000]. We describe a patient with CS, with partial GH deficiency and hypoglycemia.…”

“…Further, supravalvar pulmonary stenosis in CS has only been documented once before . Delrue et al [2003] reported seizure activity in 20% of patients with CS. The initial generalized seizures in our patient can be explained on the basis of documented hypoglycemia, and, in view of the MRI brain scan, we surmise that the subsequent myoclonic jerks may be the result of an acquired brain insult secondary to his hypoglycemic episodes.…”

Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations

“…[32][33][34][35] Electroencephalogram abnormalities are seen in approximately one third of individuals; between 20% and 50% have seizures. 36,37 Seven of 10 individuals ages 3-29 years undergoing polysomnography in the sleep laboratory had obstructive events. 38 Dental abnormalities, including enamel defects, occur frequently.…”

Educational Implications of Costello Syndrome: The Team Approach

“…Shortness of stature is a common characteristic as well as the development of scoliosis or kyphosis as the child matures (Lin, 2003;Yassir, Grottkau, & Goldberg, 2003). Among other possible physical markers are Chiari malformation and the presence of rare tumors and/or cancers such as Rhabdomyosarcoma or bladder cancer (Delrue Chateil, Arveiler, & Lacombe, 2003;Gripp et al, 2002). Chiari malformations are structural defects in the bony structure that holds the cerebellum and part of the brain stem.…”