CLINICAL REPORT
Unusual Prenatal Presentation of Rubinstein–Taybi Syndrome: A Case Report Maria Francesca Bedeschi,1* Beatrice Letizia Crippa,2 Lorenzo Colombo,2 Sophie Guez,3 Marta Cerruti,3 Roberto Fogliani,4 Cristina Gervasini,5 and Faustina Lalatta1 1
Medical Genetics Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
2
NICU, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Trasplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Universita` degli Studi di Milano, Milan, Italy 3
4
Obstetrics and Gynecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Dept of Medicine, Surgery and Dentistry, Universita` degli Studi di Milano, Milan, Italy
5
Manuscript Received: 16 January 2014; Manuscript Accepted: 7 May 2014
Rubinstein–Taybi syndrome (RTS) is a rare multiple congenital anomalies-intellectual disability syndrome. The diagnosis is made after birth and based on the detection of signs such as growth and developmental delay, minor facial anomalies, and broad thumbs and halluces. It is rare to suspect RTS during the prenatal period. We report here the approach to a patient with RTS whose pregnancy was complicated by multiple congenital anomalies. However, in the presence of the broad thumb and facial anomalies, we were able to suggest the correct diagnosis. The RTS was confirmed at birth and the molecular analysis of the major causative gene revealed a previously unreported heterozygous truncating mutation of CREBBP. This report provides new knowledge of the fetal phenotype of RTS. Ó 2014 Wiley Periodicals, Inc.
Key words: Rubinstein–Taybi syndrome; RTS; prenatal diag-
How to Cite this Article: Bedeschi MF, Crippa BL, Colombo L, Guez S, Cerruti M, Fogliani R, Gervasini C, Lalatta F. 2014. Unusual prenatal presentation of Rubinstein–Taybi syndrome: A case report. Am J Med Genet Part A. 164A:2663–2666.
To the best of our knowledge, it is difficult to make the diagnosis of this rare syndrome during the prenatal period. In this report, we discuss a case in which pregnancy was complicated by multiple ultrasound anomalies, some of these not usually associated with the diagnosis of RTS.
nosis; broad thumb-hallux; distinctive face; CNS malformation
CLINICAL REPORT INTRODUCTION Rubinstein–Taybi syndrome (RTS; OMIM #180849) is a welldefined condition characterized by multiple congenital anomalies and intellectual disability [Hennekam, 2006]. RTS has a prevalence of 1 in 10,0000–12,5000 live births and an autosomal dominant pattern of transmission.The syndrome is known to be caused by heterozygous mutations in either CREBBP (chr. # 16p13.3) or EP300 (chr # 22q13.2), which code for histone acetyltransferases (HATs) [Bentivegna et al., 2006; Roelfsema and Peters, 2007]. The diagnosis is based on the detection of signs such as growth and developmental delay, minor facial anomalies, limb abnormalities, and broad thumbs and halluces. The facial appearance is striking with highly arched eyebrows, long eyelashes, down-slanting palpebral fissures, broad nasal bridge, and overhanging nasal tip with the septum extending well below the nasal alae, prominent columella, high palate and mild micrognathia [Hennekam, 2006].
Ó 2014 Wiley Periodicals, Inc.
The propositus was the second-child of nonconsanguineous healthy Caucasian parents. The first sibling was normal and healthy and the family history was unremarkable and negative for mental retardation and birth defects. The couple was referred for genetic counseling because of megacystis (9.4 mm 8.7 mm diameter) and cysts of the umbilical cord (20 mm 16 mm) observed at 18 weeks of gestation by 2D-US fetal ultrasound. Exposure to medications or known teratogenic agents was excluded. Cytogenetic analysis perConflict of interest: none. Correspondence to: Dr. Maria Francesca Bedeschi, Medical Genetics Unit-Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milan, Italy. E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 29 July 2014 DOI 10.1002/ajmg.a.36684
2663
2664
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
FIG. 1. At 25th week GA an MRI examination performed using ultrafast T2-weighted 4 mm-thick multiplanar sections, revealed agenesis of the posterior 3rd of the corpus callosum and showed dubious subcortical heterotopic band, mild hypoplasia, and cranial rotation of the cerebellar vermis and thickened nuchal fold.
formed on a chorionic villous sample showed a normal male karyotype (46, XY). At the 20th week a 2D-US evaluation excluded megacystis and cysts of the umbilical cord but, instead, showed dysgenesis of the corpus callosum. At the 25th week, an MRI examination performed using ultrafast T2-weighted 4 mm-thick multiplanar sections, confirmed the suspected agenesis of the posterior third of the corpus callosum and revealed a doubtful subcortical band heterotopia, mild hypoplasia and cranial rotation of the cerebellar vermis, and a thickened nuchal fold (Fig. 1). At the 28th week a 3D-US revealed minor facial and limb anomalies including broad nasal bridge and tip with columella extending
below the nasal alae, long philtrum, and broad thumb (Fig. 2). These features allowed us to hypothesize RTS. Following extensive counseling the couple decided to continue the pregnancy. The molecular testing was not performed. A fetal brain MRI was repeated at the 33rd week revealing cranial circumference less than 3rd centile, persistence of the globally thinned corpus callosum with a resulting deformity of the lateral ventricles and bilateral malrotation of hippocampus. A cyst in the periventricular region of the thalamus-caudate sulcus was also reported and persistent anomalies of the cerebellar vermis were confirmed. Polyhydramnios was detected at the 35th week.
FIG. 2. 3D-US evaluation at the 28th week of GA showed facial anomalies such as broad nasal bridge and tip with columella extending below the nasal alae, long philtrum, and broad thumb.
BEDESCHI ET AL.
2665
FIG. 3. Clinical features of the child at birth include square face, low forehead hairline, hypertelorism, thick eyebrows, broad nasal bridge and prominent nasal tip with the columella extending below the alae nasi, long and flat philtrum, thin vermilion of the lips, and low-set ears.
The infant was delivered by cesarean at the 38th week GA with a birth weight (BW) of 2.920 kg (23rd centile), a body length of 47.50 cm (3rd centile), occipito-frontal circumference of 32 cm (3rd–10th centile). Apgar scores were 8–9 at the first and the fifth minutes. The child had a low frontal hairline, apparent hypertelorism, thick eyebrows, a broad nasal bridge, a prominent nasal tip with the columella extending below the nasal alae, a long and flat philtrum, thin vermilion to the lips, low-set ears, broad thumbs, pre and post-axial bilateral polydactyly of feet (Figs. 3 and 4). An ophthalmological examination revealed right sclerocornea, bilateral megalocornea, cataracts and glaucoma. Cerebral ultrasound and MRI confirmed the agenesis of the posterior third of the corpus callosum, subcortical band heterotopia, mild hypoplasia and cranial rotation of the cerebellar vermis. X-rays of the feet revealed bilateral distal phalanx bifida of the first and the fifth finger. On follow-up at 1 and 2 years he showed growth and developmental delay.
FIG. 4. Note broad thumb, pre and post-axial polydactyly of one foot.
MOLECULAR RESULTS The entire coding region of CREBBP was screened by DHPLC. An abnormal conformer in exon, 18 fragments were detected and sequenced. A c.3474G >A change converting the TGG codon (Trp) in a TGA stop codon predicting CBP truncation at residue 1158, located in the Bromodomain, was identified. This truncating mutation has not yet been described. Consistent with its pathogenetic nature, both parents of the affected newborn showed a CREBBP normal sequence.
DISCUSSION The diagnosis of RTS is usually made at birth or during infancy. In 56% of the patients it is confirmed by molecular genetic testing. In the remaining 44% it is based only on the clinical data [Schorry et al., 2008].
2666
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
TABLE I. Clinical Features Showed in Prenatal Period Facial anomalies
Case 1, Greco et al. [2009] Prominent beaked, nose moderate micrognathia
Limb anomalies CNS anomalies
Broad and deviated thumbs, abducted toes Severe cerebellar hypoplasia
Urinary anomalies Other anomalies Polyhydramnios Karyotype Diagnosis confirmed
None None Detected at 20 weeks of GA 46,XY On necropsy, after elective abortion, no molecular analysis Association of facial with limb anomalies
Features suggesting the prenatal diagnosis
In literature, only one case was reported in which the RTS diagnosis was hypothesized prenatally after the detection of sonographic suspicious findings and confirmed clinically after necropsy [Greco et al., 2009]. However in this case molecular analysis was not carried out. As shown in Table I, both cases presented with posterior fossa anomalies and, in our case, with other CNS abnormalities such as partial agenesis of corpus callosum, malrotated hippocampus and microcephaly. Moreover, polyhydramnios reflected the neurologic impairment of two fetuses. Posterior fossa malformations are among the most common brain anomalies identified by current fetal imaging techniques. They are a heterogeneous group of CNS malformations which can occur as sporadic or familial, but they are also frequently part of syndromes and associations. In fact several conditions with posterior fossa anomalies and Dandy-Walker malformation (DWM) were considered in differential diagnosis, with about 342 and 133 syndromes in OMD, respectively. Posterior fossa anomalies have very rarely been described in Rubinstein– Taybi syndrome and have never been associated with megacystis or umbilical cord cystis [Bonioli et al., 1989; Mazzone et al., 1989; Agarwal et al., 2009; Pandya et al., 2009]. In one report of RTS DWM was detected in association with a large bilateral coloboma of the iris, ciliary body, choroid, and retina including an optic nerve with chorioretinal atrophy [Bonioli et al., 1989]. In RTS cranial malformations include microcephaly, delayed closure of anterior fontanel, and absence of corpus callosum. In all these cases the RTS diagnosis was made only after birth. In our patient, even in the presence of some anomalies not usually associated with RTS, the simultaneous presence of broad thumb and distinctive facial features raised the prenatal suspicion of RTS as previously reported only by Greco et al. The fetal presentation of RTS can be extremely unpredictable. This syndrome is rare and, most of the time, findings detected during the prenatal period cannot dictate specific molecular testing. For this reason, the specific prenatal diagnosis was reported only once in literature.
Case 2, our patient Broad nasal bridge and tip columella below the nasal alae, long philtrum Broad thumbs Agenesis of corpus callosum, Dandy–Walker malformation, malrotation of hippocampus Megacystis (excluded at the 20th week of GA) Cyst of umbilical cord Detected at 35 weeks of GA 46,XY After birth, clinically and by molecular analysis Association of facial with limb anomalies
However, our report underlines the importance of considering the hypothesis of RST in a genetic counseling in presence of broad thumbs and the facial feature reported above, even if part of an unusual and more complex presentation.
REFERENCES Agarwal R, Aggarwal R, Kabra M, Deorari AK. 2009. Dandy-Walker malformation in Rubinstein-Taybi syndrome: A rare association. Clin Dysmorphol 11:223–224. Bentivegna A, Milani D, Gervasini C, Castronovo P, Mottadelli F, Manzini S, Colapietro P, Giordano L, Atzeri F, Divizia MT, Uzielli ML, Neri G, Bedeschi MF, Faravelli F, Selicorni A, Larizza L. 2006. Rubinstein-Taybi syndrome: Spectrum of CREBBP mutations in Italian patients. BMC Med Genet 7:77. Bonioli E, Bellini C, Di Stefano A. 1989. Unusual association: DandyWalker like malformation in Rubinstein-Taybi syndrome. Am J Med Genet 33:420–421. Greco E, Sglavo G, Paladini D. 2009. Preanatal sonographic diagnosis of Rubinstein-Taybi syndrome. J Ultrasound Med 28:669–672. Hennekam RC. 2006. Rubinstein-Taybi syndrome. Eur J Hum Genet 14:981–985. Mazzone D, Milana A, Partico` G. 1989. Rubinstein-Taybi syndrome associated with Dandy-Walker cyst. Case report in a newborn. J Perinat Med 17:381–384. Pandya N, Rebello G, Deshpande C. 2009. Dandy-Walker variant an association with Rubinstein-Taybi syndrome. Internet J Pediatr Neonatol 10:7. Roelfsema JH, Peters DJ. 2007. Rubinstein-Taybi syndrome: Clinical and molecular overview. Expert Rev Mol Med 9:1–16. Schorry EK, Keddache M, Lanphear N, Rubinstein JH, Srodulski S, Flercher D, Blough-Pfau RI, Grabowski GA. 2008. Genotype-phenotype correlations in Rubinstein-Taybi syndrome. Am J Med Genet Part A 146A:2512–2525.
Unusual Prenatal Presentation of Rubinstein–Taybi Syndrome: A Case Report Maria Francesca Bedeschi,1* Beatrice Letizia Crippa,2 Lorenzo Colombo,2 Sophie Guez,3 Marta Cerruti,3 Roberto Fogliani,4 Cristina Gervasini,5 and Faustina Lalatta1 1
Medical Genetics Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
2
NICU, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Trasplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Universita` degli Studi di Milano, Milan, Italy 3
4
Obstetrics and Gynecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Dept of Medicine, Surgery and Dentistry, Universita` degli Studi di Milano, Milan, Italy
5
Manuscript Received: 16 January 2014; Manuscript Accepted: 7 May 2014
Rubinstein–Taybi syndrome (RTS) is a rare multiple congenital anomalies-intellectual disability syndrome. The diagnosis is made after birth and based on the detection of signs such as growth and developmental delay, minor facial anomalies, and broad thumbs and halluces. It is rare to suspect RTS during the prenatal period. We report here the approach to a patient with RTS whose pregnancy was complicated by multiple congenital anomalies. However, in the presence of the broad thumb and facial anomalies, we were able to suggest the correct diagnosis. The RTS was confirmed at birth and the molecular analysis of the major causative gene revealed a previously unreported heterozygous truncating mutation of CREBBP. This report provides new knowledge of the fetal phenotype of RTS. Ó 2014 Wiley Periodicals, Inc.
Key words: Rubinstein–Taybi syndrome; RTS; prenatal diag-
How to Cite this Article: Bedeschi MF, Crippa BL, Colombo L, Guez S, Cerruti M, Fogliani R, Gervasini C, Lalatta F. 2014. Unusual prenatal presentation of Rubinstein–Taybi syndrome: A case report. Am J Med Genet Part A. 164A:2663–2666.
To the best of our knowledge, it is difficult to make the diagnosis of this rare syndrome during the prenatal period. In this report, we discuss a case in which pregnancy was complicated by multiple ultrasound anomalies, some of these not usually associated with the diagnosis of RTS.
nosis; broad thumb-hallux; distinctive face; CNS malformation
CLINICAL REPORT INTRODUCTION Rubinstein–Taybi syndrome (RTS; OMIM #180849) is a welldefined condition characterized by multiple congenital anomalies and intellectual disability [Hennekam, 2006]. RTS has a prevalence of 1 in 10,0000–12,5000 live births and an autosomal dominant pattern of transmission.The syndrome is known to be caused by heterozygous mutations in either CREBBP (chr. # 16p13.3) or EP300 (chr # 22q13.2), which code for histone acetyltransferases (HATs) [Bentivegna et al., 2006; Roelfsema and Peters, 2007]. The diagnosis is based on the detection of signs such as growth and developmental delay, minor facial anomalies, limb abnormalities, and broad thumbs and halluces. The facial appearance is striking with highly arched eyebrows, long eyelashes, down-slanting palpebral fissures, broad nasal bridge, and overhanging nasal tip with the septum extending well below the nasal alae, prominent columella, high palate and mild micrognathia [Hennekam, 2006].
Ó 2014 Wiley Periodicals, Inc.
The propositus was the second-child of nonconsanguineous healthy Caucasian parents. The first sibling was normal and healthy and the family history was unremarkable and negative for mental retardation and birth defects. The couple was referred for genetic counseling because of megacystis (9.4 mm 8.7 mm diameter) and cysts of the umbilical cord (20 mm 16 mm) observed at 18 weeks of gestation by 2D-US fetal ultrasound. Exposure to medications or known teratogenic agents was excluded. Cytogenetic analysis perConflict of interest: none. Correspondence to: Dr. Maria Francesca Bedeschi, Medical Genetics Unit-Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milan, Italy. E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 29 July 2014 DOI 10.1002/ajmg.a.36684
2663
2664
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
FIG. 1. At 25th week GA an MRI examination performed using ultrafast T2-weighted 4 mm-thick multiplanar sections, revealed agenesis of the posterior 3rd of the corpus callosum and showed dubious subcortical heterotopic band, mild hypoplasia, and cranial rotation of the cerebellar vermis and thickened nuchal fold.
formed on a chorionic villous sample showed a normal male karyotype (46, XY). At the 20th week a 2D-US evaluation excluded megacystis and cysts of the umbilical cord but, instead, showed dysgenesis of the corpus callosum. At the 25th week, an MRI examination performed using ultrafast T2-weighted 4 mm-thick multiplanar sections, confirmed the suspected agenesis of the posterior third of the corpus callosum and revealed a doubtful subcortical band heterotopia, mild hypoplasia and cranial rotation of the cerebellar vermis, and a thickened nuchal fold (Fig. 1). At the 28th week a 3D-US revealed minor facial and limb anomalies including broad nasal bridge and tip with columella extending
below the nasal alae, long philtrum, and broad thumb (Fig. 2). These features allowed us to hypothesize RTS. Following extensive counseling the couple decided to continue the pregnancy. The molecular testing was not performed. A fetal brain MRI was repeated at the 33rd week revealing cranial circumference less than 3rd centile, persistence of the globally thinned corpus callosum with a resulting deformity of the lateral ventricles and bilateral malrotation of hippocampus. A cyst in the periventricular region of the thalamus-caudate sulcus was also reported and persistent anomalies of the cerebellar vermis were confirmed. Polyhydramnios was detected at the 35th week.
FIG. 2. 3D-US evaluation at the 28th week of GA showed facial anomalies such as broad nasal bridge and tip with columella extending below the nasal alae, long philtrum, and broad thumb.
BEDESCHI ET AL.
2665
FIG. 3. Clinical features of the child at birth include square face, low forehead hairline, hypertelorism, thick eyebrows, broad nasal bridge and prominent nasal tip with the columella extending below the alae nasi, long and flat philtrum, thin vermilion of the lips, and low-set ears.
The infant was delivered by cesarean at the 38th week GA with a birth weight (BW) of 2.920 kg (23rd centile), a body length of 47.50 cm (3rd centile), occipito-frontal circumference of 32 cm (3rd–10th centile). Apgar scores were 8–9 at the first and the fifth minutes. The child had a low frontal hairline, apparent hypertelorism, thick eyebrows, a broad nasal bridge, a prominent nasal tip with the columella extending below the nasal alae, a long and flat philtrum, thin vermilion to the lips, low-set ears, broad thumbs, pre and post-axial bilateral polydactyly of feet (Figs. 3 and 4). An ophthalmological examination revealed right sclerocornea, bilateral megalocornea, cataracts and glaucoma. Cerebral ultrasound and MRI confirmed the agenesis of the posterior third of the corpus callosum, subcortical band heterotopia, mild hypoplasia and cranial rotation of the cerebellar vermis. X-rays of the feet revealed bilateral distal phalanx bifida of the first and the fifth finger. On follow-up at 1 and 2 years he showed growth and developmental delay.
FIG. 4. Note broad thumb, pre and post-axial polydactyly of one foot.
MOLECULAR RESULTS The entire coding region of CREBBP was screened by DHPLC. An abnormal conformer in exon, 18 fragments were detected and sequenced. A c.3474G >A change converting the TGG codon (Trp) in a TGA stop codon predicting CBP truncation at residue 1158, located in the Bromodomain, was identified. This truncating mutation has not yet been described. Consistent with its pathogenetic nature, both parents of the affected newborn showed a CREBBP normal sequence.
DISCUSSION The diagnosis of RTS is usually made at birth or during infancy. In 56% of the patients it is confirmed by molecular genetic testing. In the remaining 44% it is based only on the clinical data [Schorry et al., 2008].
2666
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
TABLE I. Clinical Features Showed in Prenatal Period Facial anomalies
Case 1, Greco et al. [2009] Prominent beaked, nose moderate micrognathia
Limb anomalies CNS anomalies
Broad and deviated thumbs, abducted toes Severe cerebellar hypoplasia
Urinary anomalies Other anomalies Polyhydramnios Karyotype Diagnosis confirmed
None None Detected at 20 weeks of GA 46,XY On necropsy, after elective abortion, no molecular analysis Association of facial with limb anomalies
Features suggesting the prenatal diagnosis
In literature, only one case was reported in which the RTS diagnosis was hypothesized prenatally after the detection of sonographic suspicious findings and confirmed clinically after necropsy [Greco et al., 2009]. However in this case molecular analysis was not carried out. As shown in Table I, both cases presented with posterior fossa anomalies and, in our case, with other CNS abnormalities such as partial agenesis of corpus callosum, malrotated hippocampus and microcephaly. Moreover, polyhydramnios reflected the neurologic impairment of two fetuses. Posterior fossa malformations are among the most common brain anomalies identified by current fetal imaging techniques. They are a heterogeneous group of CNS malformations which can occur as sporadic or familial, but they are also frequently part of syndromes and associations. In fact several conditions with posterior fossa anomalies and Dandy-Walker malformation (DWM) were considered in differential diagnosis, with about 342 and 133 syndromes in OMD, respectively. Posterior fossa anomalies have very rarely been described in Rubinstein– Taybi syndrome and have never been associated with megacystis or umbilical cord cystis [Bonioli et al., 1989; Mazzone et al., 1989; Agarwal et al., 2009; Pandya et al., 2009]. In one report of RTS DWM was detected in association with a large bilateral coloboma of the iris, ciliary body, choroid, and retina including an optic nerve with chorioretinal atrophy [Bonioli et al., 1989]. In RTS cranial malformations include microcephaly, delayed closure of anterior fontanel, and absence of corpus callosum. In all these cases the RTS diagnosis was made only after birth. In our patient, even in the presence of some anomalies not usually associated with RTS, the simultaneous presence of broad thumb and distinctive facial features raised the prenatal suspicion of RTS as previously reported only by Greco et al. The fetal presentation of RTS can be extremely unpredictable. This syndrome is rare and, most of the time, findings detected during the prenatal period cannot dictate specific molecular testing. For this reason, the specific prenatal diagnosis was reported only once in literature.
Case 2, our patient Broad nasal bridge and tip columella below the nasal alae, long philtrum Broad thumbs Agenesis of corpus callosum, Dandy–Walker malformation, malrotation of hippocampus Megacystis (excluded at the 20th week of GA) Cyst of umbilical cord Detected at 35 weeks of GA 46,XY After birth, clinically and by molecular analysis Association of facial with limb anomalies
However, our report underlines the importance of considering the hypothesis of RST in a genetic counseling in presence of broad thumbs and the facial feature reported above, even if part of an unusual and more complex presentation.
REFERENCES Agarwal R, Aggarwal R, Kabra M, Deorari AK. 2009. Dandy-Walker malformation in Rubinstein-Taybi syndrome: A rare association. Clin Dysmorphol 11:223–224. Bentivegna A, Milani D, Gervasini C, Castronovo P, Mottadelli F, Manzini S, Colapietro P, Giordano L, Atzeri F, Divizia MT, Uzielli ML, Neri G, Bedeschi MF, Faravelli F, Selicorni A, Larizza L. 2006. Rubinstein-Taybi syndrome: Spectrum of CREBBP mutations in Italian patients. BMC Med Genet 7:77. Bonioli E, Bellini C, Di Stefano A. 1989. Unusual association: DandyWalker like malformation in Rubinstein-Taybi syndrome. Am J Med Genet 33:420–421. Greco E, Sglavo G, Paladini D. 2009. Preanatal sonographic diagnosis of Rubinstein-Taybi syndrome. J Ultrasound Med 28:669–672. Hennekam RC. 2006. Rubinstein-Taybi syndrome. Eur J Hum Genet 14:981–985. Mazzone D, Milana A, Partico` G. 1989. Rubinstein-Taybi syndrome associated with Dandy-Walker cyst. Case report in a newborn. J Perinat Med 17:381–384. Pandya N, Rebello G, Deshpande C. 2009. Dandy-Walker variant an association with Rubinstein-Taybi syndrome. Internet J Pediatr Neonatol 10:7. Roelfsema JH, Peters DJ. 2007. Rubinstein-Taybi syndrome: Clinical and molecular overview. Expert Rev Mol Med 9:1–16. Schorry EK, Keddache M, Lanphear N, Rubinstein JH, Srodulski S, Flercher D, Blough-Pfau RI, Grabowski GA. 2008. Genotype-phenotype correlations in Rubinstein-Taybi syndrome. Am J Med Genet Part A 146A:2512–2525.
