Abstract
Objective
Rubinstein–Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized
by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic
features. In 25% of patients seizures have been described, and in about 66% a wide
range of EEG abnormalities, but studies on neurological features are scant and dated.
The aim of this study is to describe the electroclinical phenotype of twenty-three
patients with RSTS, and to try to correlate electroclinical features with neuroradiological,
cognitive and genetic features.
Patients and methods
Electroclinical features of twenty-three patients with RSTS (age between18 months and 20 years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and
brain MRI in nineteen patients. All subjects received cognitive evaluation.
Results
EEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent
in sleep, characterized by slow monomorphic activity on posterior regions was also
observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four
percentage of patients had brain MRI abnormalities, involving corpus callosum and/or
posterior periventricular white matter. Average General Quotient (GQ) was 52, while
average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous
electroclinical pattern was observed mainly in patients with more severe neuroradiologic
findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No
genotype-phenotype correlations were found.
Conclusion
The specific electroclinical and neuroradiological features described may be part
of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify
its significance and impact on diagnosis, prognosis and clinical management of RSTS
patients.
Keywords
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References
- Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome.Am J Dis Child. 1963; 105: 588-608
- Rubinstein–Taybi syndrome caused by mutations in the transcriptional co-activator CBP.Nature. 1995; 376: 348-351
- Genetic heterogeneity in Rubinstein–Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.Am J Hum Genet. 2005; 76: 572-580
- Rubinstein–Taybi syndrome: clinical profile of 11 patients and review of literature.Indian J Hum Genet. 2012; 18: 161-166
- Rubinstein–Taybi syndrome: a natural history study.Am J Med Genet Suppl. 1990; 6: 30-37
- Psychological and speech studies in Rubinstein–Taybi syndrome.Am J Ment Retard. 1992; 96: 645-660
- Rubinstein–Taybi syndrome. Review of 732 cases and analysis of the typical traits.Eur Rev Med Pharmacol Sci. 1998; 2: 81-87
- Broad thumb-hallux (Rubinstein–Taybi) syndrome 1957–1988.Am J Med Genet Suppl. 1990; 6: 3-16
- Rubinstein–Taybi syndrome: clinical and molecular cytogenetic studies.Acta Paediatr Taiwan. 2005; 46: 143-148
- Rubinstein–Taybi syndrome.J Med Genet. 1987; 24: 562-566
- Congenital anomaly of cervical vertebrae is a major complication of Rubinstein–Taybi syndrome.Am J Med Genet. 2005; 135: 130-133
- Rubinstein–Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?.Am J Med Genet. 2010; 152: 479-483
- Identical twin sisters with Rubinstein–Taybi syndrome associated with Chiari malformations and syrinx.Am J Med Genet. 2011; 155: 2766-2770
- The association of neural axis and craniovertebral junction anomalies with scoliosis in Rubinstein–Taybi syndrome.Child Nerv Syst. 2012; 28: 2163-2168
- Rubinstein–Taybi syndrome in children with tethered spinal cord.J Neurosurg. 2006; 105: 261-264
- Duplication 16p13.3 and the CREBBP gene: confirmation of the phenotype.Eur J Med Genet. 2013; 56: 26-31
- Leiter international performance scale-revised: examiner’s manual.in: Roid G.H. Miller L.J. Leiter international performance scale-revised. Stoelting Co., Wood Dale1997
- The abilities of babies: a study in mental measurement.The Test Agency Ltd., Cournswood House1986
- Epilepsy in Angelman syndrome.Seizure. 2008; 17: 211-217
- Epilepsy in Rett Syndrome: association between phenotype and genotype and implications for practice.Seizure. 2011; 20: 646-649
- Spectrum of epilepsy and electroencephalogram patterns in Wolf–Hirschhorn syndrome: experience with 87 patients.Dev Med Child Neurol. 2009; 51: 373-380
- The inv dup (15) or idic (15) syndrome (Tetrasomy 15q).Orphanet J Rare Dis. 2008; 3: 30
- Seizures and EEG features in 74 patients with genetic-dysmorphic syndromes.Am J Med Genet. 2014; 164: 3154-3161
- Spectrum of grosse deletion and point mutation in Italian RSTS syndrome.BMC Med Genet. 2006; 7: 77
- Characterization of 14 novel deletions underlying Rubinstein–Taybi syndrome: an update of the CREBBP deletion repertoire.Hum Genet. 2015; 134: 613-626
- Insights into genotype-phenotype correlations from CREBBP point mutation screening in a cohort of 46 Rubinstein–Taybi Syndrome patients.Clin Genet. 2015; 88: 431-440
- High frequency of copy number imbalances in Rubinstein–Taybi patients negative to CREBBP mutational analysis.Eur J Hum Genet. 2010; 18: 768-775
Article info
Publication history
Published online: February 08, 2016
Accepted:
December 10,
2015
Received in revised form:
December 9,
2015
Received:
June 12,
2015
Identification
Copyright
© 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
