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Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management.

Milani D, Manzoni FM, Pezzani L, Ajmone P, Gervasini C, Menni F, Esposito S - Ital J Pediatr (2015)

Bottom Line: RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation.RSTS is primarily characterized by delayed growth in height and weight, microcephaly, dysmorphic facial features, and broad thumbs and big toe.However, the pathogenesis and genotype-phenotype associations of RSTS are largely unknown.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122, Milano, Italy. donatella.milani@policlinico.mi.it.

ABSTRACT

Background: Rubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation. However, no standard diagnostic criteria are available for RSTS. In this review, we summarized the clinical features and genetic basis of RSTS and highlighted areas for future studies on an appropriate diagnostic protocol and follow-up care for RSTS.

Discussion: RSTS is primarily characterized by delayed growth in height and weight, microcephaly, dysmorphic facial features, and broad thumbs and big toe. Over 90% RSTS individuals with disabilities survive to adulthood, but healthcare for these patients is particularly complex, time-consuming, and costly. In addition, no standard diagnostic criteria and follow-up care guidelines are available for RSTS. It has been shown that mutations in the genes encoding the cyclic-AMP-regulated enhancer binding protein (CREBBP) and the E1A-binding protein p300 (EP300) contributed to the development of RSTS. Therefore, genetic tests are useful for the diagnosis of RSTS, although most RSTS cases are currently diagnosed based on clinical features. The clinical features of RSTS have been extensively studied, which significantly contributes to the diagnosis of this extremely rare syndrome. However, the pathogenesis and genotype-phenotype associations of RSTS are largely unknown. Therefore, multicenter studies and international cooperation are highlighted for better understanding of this disease, establishing standard diagnostic criteria, and providing professional management and follow-up care of RSTS.

No MeSH data available.


Related in: MedlinePlus

Typical facies of a RSTS patient, including arched eyebrows, slanted palpebral fissures, protruding beaked nose with columella below alae nasi, arched palate, mild micrognathia, labial commissures facing upward, teeth anomalies, and an atypical smile (“grimacing”) with nearly completely closed eyes.
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Fig1: Typical facies of a RSTS patient, including arched eyebrows, slanted palpebral fissures, protruding beaked nose with columella below alae nasi, arched palate, mild micrognathia, labial commissures facing upward, teeth anomalies, and an atypical smile (“grimacing”) with nearly completely closed eyes.

Mentions: RSTS is characterized by slow development of height and weight, microcephaly, dysmorphic facial features, broad thumbs, and big toes [18]. The prenatal development is normal, with average or near-normal growth parameters at birth. The growth charts typically approach the lower limits of normality in the first postnatal period, primarily reflecting hypo-feeding exacerbated by gastro-esophageal reflux. Subsequently, the tendency of overweight or obesity (earlier in males than females) can be observed during adolescence. Specific and recently reviewed growth charts are essential for appropriate assessment of the growth of affected individuals [18]. Facial features are primarily characterized by low frontal hairline, arched/thick eyebrows, downslanting of palpebral fissures, a protruding beaked nose with columella below alae nasi, dysplastic and low-set ears, an arched palate, mild micrognathia, dental anomalies (altered conformation, malocclusion, and overcrowding of teeth), and atypical smile (“grimacing”) with nearly completely closed eyes (Figure 1). The feet and hands typically present an enlarged first finger and clinodactyly of the fifth finger (Figure 2), whereas polydactyly with bifid thumbs and first toes is rarely observed. Other skeletal anomalies include abducted thumbs, vertebral anomalies, ligamentous laxity, severe and prolonged aseptic inflammation of the femur head, anomalies similar with Perthes disease (3%), and occasionally slipped capital femoral epiphysis [19,20]. Particularly, high risk of cervical vertebral abnormalities (instability of C1–C2, os odontoideum, hypoplasia of the dens, fusion of the cervical vertebrae) has been reported [21-23], with possible stenosis at the craniovertebral junction, which may cause cervical myelopathy. Complex neuroradiological issues including corpus callosum dysgenesis (17%) [24,25], Chiari type I malformation with or without syringomyelia [25-28], Dandy Walker malformation and hydrocephalus [29,30], and tethered cord [27,31] have been reported and are still under investigation. Cerebrovascular abnormalities such as spontaneous dissection of the supraaortic arteries [32] and cerebral infarction due to dissecting aneurysm of the anterior cerebral artery have also been reported [33]. However, any organ can be affected in RSTS patients. Possible malformations, medical problems, and complications include (Table 1):


Rubinstein-Taybi syndrome: clinical features, genetic basis, diagnosis, and management.

Milani D, Manzoni FM, Pezzani L, Ajmone P, Gervasini C, Menni F, Esposito S - Ital J Pediatr (2015)

Typical facies of a RSTS patient, including arched eyebrows, slanted palpebral fissures, protruding beaked nose with columella below alae nasi, arched palate, mild micrognathia, labial commissures facing upward, teeth anomalies, and an atypical smile (“grimacing”) with nearly completely closed eyes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308897&req=5

Fig1: Typical facies of a RSTS patient, including arched eyebrows, slanted palpebral fissures, protruding beaked nose with columella below alae nasi, arched palate, mild micrognathia, labial commissures facing upward, teeth anomalies, and an atypical smile (“grimacing”) with nearly completely closed eyes.
Mentions: RSTS is characterized by slow development of height and weight, microcephaly, dysmorphic facial features, broad thumbs, and big toes [18]. The prenatal development is normal, with average or near-normal growth parameters at birth. The growth charts typically approach the lower limits of normality in the first postnatal period, primarily reflecting hypo-feeding exacerbated by gastro-esophageal reflux. Subsequently, the tendency of overweight or obesity (earlier in males than females) can be observed during adolescence. Specific and recently reviewed growth charts are essential for appropriate assessment of the growth of affected individuals [18]. Facial features are primarily characterized by low frontal hairline, arched/thick eyebrows, downslanting of palpebral fissures, a protruding beaked nose with columella below alae nasi, dysplastic and low-set ears, an arched palate, mild micrognathia, dental anomalies (altered conformation, malocclusion, and overcrowding of teeth), and atypical smile (“grimacing”) with nearly completely closed eyes (Figure 1). The feet and hands typically present an enlarged first finger and clinodactyly of the fifth finger (Figure 2), whereas polydactyly with bifid thumbs and first toes is rarely observed. Other skeletal anomalies include abducted thumbs, vertebral anomalies, ligamentous laxity, severe and prolonged aseptic inflammation of the femur head, anomalies similar with Perthes disease (3%), and occasionally slipped capital femoral epiphysis [19,20]. Particularly, high risk of cervical vertebral abnormalities (instability of C1–C2, os odontoideum, hypoplasia of the dens, fusion of the cervical vertebrae) has been reported [21-23], with possible stenosis at the craniovertebral junction, which may cause cervical myelopathy. Complex neuroradiological issues including corpus callosum dysgenesis (17%) [24,25], Chiari type I malformation with or without syringomyelia [25-28], Dandy Walker malformation and hydrocephalus [29,30], and tethered cord [27,31] have been reported and are still under investigation. Cerebrovascular abnormalities such as spontaneous dissection of the supraaortic arteries [32] and cerebral infarction due to dissecting aneurysm of the anterior cerebral artery have also been reported [33]. However, any organ can be affected in RSTS patients. Possible malformations, medical problems, and complications include (Table 1):

Bottom Line: RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation.RSTS is primarily characterized by delayed growth in height and weight, microcephaly, dysmorphic facial features, and broad thumbs and big toe.However, the pathogenesis and genotype-phenotype associations of RSTS are largely unknown.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122, Milano, Italy. donatella.milani@policlinico.mi.it.

ABSTRACT

Background: Rubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. RSTS is characterized by typical facial features, microcephaly, broad thumbs and first toes, intellectual disability, and postnatal growth retardation. However, no standard diagnostic criteria are available for RSTS. In this review, we summarized the clinical features and genetic basis of RSTS and highlighted areas for future studies on an appropriate diagnostic protocol and follow-up care for RSTS.

Discussion: RSTS is primarily characterized by delayed growth in height and weight, microcephaly, dysmorphic facial features, and broad thumbs and big toe. Over 90% RSTS individuals with disabilities survive to adulthood, but healthcare for these patients is particularly complex, time-consuming, and costly. In addition, no standard diagnostic criteria and follow-up care guidelines are available for RSTS. It has been shown that mutations in the genes encoding the cyclic-AMP-regulated enhancer binding protein (CREBBP) and the E1A-binding protein p300 (EP300) contributed to the development of RSTS. Therefore, genetic tests are useful for the diagnosis of RSTS, although most RSTS cases are currently diagnosed based on clinical features. The clinical features of RSTS have been extensively studied, which significantly contributes to the diagnosis of this extremely rare syndrome. However, the pathogenesis and genotype-phenotype associations of RSTS are largely unknown. Therefore, multicenter studies and international cooperation are highlighted for better understanding of this disease, establishing standard diagnostic criteria, and providing professional management and follow-up care of RSTS.

No MeSH data available.


Related in: MedlinePlus