- Email: [email protected]
Affinity for Music in Wolf-Hirschhorn Syndrome: Two Case Reports
Pediatric Neurology 51 (2014) 550e552
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Affinity for Music in Wolf-Hirschhorn Syndrome: Two Case Reports Chikako Arakawa MD a, Yukihiko Fujita MD, PhD b, Tatsuo Fuchigami MD, PhD a, *, Yuki Kawamura MD a, Wakako Ishii MD a, Ayumi Endo MD, PhD a, Ryutaro Kohira MD, PhD a, Shori Takahashi MD, PhD a a b
Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan Division of Medical Education Planning, Nihon University School of Medicine, Tokyo, Japan
abstract BACKGROUND: Wolf-Hirschhorn syndrome is a congenital malformation syndrome resulting from deletion of the short arm of chromosome 4. Individuals with Wolf-Hirschhorn syndrome may have a “Greek warrior helmet” appearance, growth retardation, developmental delay, muscular hypotonia, epilepsy, and difficulty with language including verbal communication. An affinity for music has not previously been reported in these patients. PATIENTS: We describe two patients with Wolf-Hirschhorn syndrome who both have a strong affinity for music. One patient is a 20-year-old woman who likes to listen to music all day and can hum many tunes. The other patient is a 9-year-old girl who is calmed by music and received music therapy, with subsequent improvement in her communication skills (eye contact, joint attention, and vocalizations to request music). CONCLUSIONS: Individuals with Wolf-Hirschhorn syndrome may have a strong affinity for music and may benefit from music therapy. Additional studies are needed to investigate the interest in music in individuals with Wolf-Hirschhorn syndrome. Keywords: Wolf-Hirschhorn syndrome, chromosomal disorder, music, music therapy, communication skills
Pediatr Neurol 2014; 51: 550-552 Ó 2014 Elsevier Inc. All rights reserved.
Introduction
Patient Descriptions
Wolf-Hirschhorn syndrome (WHS) is a congenital malformation pattern resulting from deletion of the short arm of chromosome 4, which was first described by Cooper and Hirschhorn in 1961.1 Individuals with WHS have a variable phenotype and may present with abnormalities such as a “Greek warrior helmet” appearance, growth retardation, developmental delay, muscular hypotonia, and epilepsy. The size of the chromosome 4p deletion is highly variable,2-5 but the correlation between deletion size and phenotype remains unclear. We present two patients with WHS who have a strong affinity for music, which has not previously been reported.
Patient 1
Article History: Received April 23, 2014; Accepted in final form July 9, 2014 * Communications should be addressed to: Dr. Fuchigami; Department of Pediatrics and Child Health; Nihon University School of Medicine; 30-1 Oyaguchi-Kamicho; Itabashi-ku, Tokyo 173-8610, Japan. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.07.012
This 20-year-old woman is the second child of healthy, nonconsanguineous parents. She was born by uncomplicated vaginal delivery at 41 weeks of gestation with a birth weight of 2305 g. She achieved head control at 5 months, sitting at 23 months, and independent walking at 3 years of age. She developed recurrent otitis media with effusion during her childhood. No major organ anomalies were detected. The patient characteristics are listed in the Table. She presented with status epilepticus with fever at age 9 months and subsequently developed simple and/or complex partial seizures up to eight times daily, triggered by fever or bathing. Zonisamide therapy was tried initially but did not control the seizures, and her medications were changed to carbamazepine, valproate, and clonazepam. The seizures decreased in frequency to two to three times per year at age 4 years and stopped at age 13 years. She continues to take the same three antiepileptic medications. At 7 years of age, brain magnetic resonance imaging (MRI) was normal (Figure A), and chromosomal analysis using fluorescence in situ hybridization revealed a karyotype of 46,XX.ish del(4)(p16.3p16.3)(D4S96).
C. Arakawa et al. / Pediatric Neurology 51 (2014) 550e552
551
TABLE. Characteristics of Two Patients With Wolf-Hirschhorn Syndrome
Characteristics
Age (yr)
4p Deletion Location
Gestation, Birth Weight
Major Dysfunction
Age at First Seizure
Seizure Triggers
Admissions for Seizures
Age at Last Seizure
Patient 1
20
4p16.3
41 wk, 2305 g (2.2 SD)
Otitis media, eating difficulty
9 month
Fever, bathing
1
13 year
Patient 2
9
4p16
38 wk, 2120 g (1.9 SD)
Atrial septal defect, vesicoureteral reflux, clubfoot, otitis media, eating difficulty
5 month
Fever
6
34 month
Abbreviation: SD ¼ Standard deviation
At age 18 years of age, her intelligence score on the Tanaka-Binet test (the Japanese version of the Stanford-Binet intelligence test)6 was 17. Since leaving high school, she has worked at facilities that provide employment for handicapped people. She can eat solids and thickened liquids, but cannot swallow water. She understands a few simple words such as “stop” and “come,” but does not speak any words. Her mother first reported an affinity for music at age 2 years 3 months, during the patient’s first admission to our hospital. She likes to hum and listen to music all day, and if the music stops, she pinches her mother to indicate that she wants it to restart. She appears to enjoy humming and hums seasonal tunes at Christmas time. Her mother reported that the patient can hum over 100 tunes and that she learned to hum a tune that her teacher had improvised and played only once in the classroom. It therefore seems that she can remember and hum some tunes after hearing them only once. The patient has not participated in music therapy. She continues to live at home with her family.
Patient 2 This is a 9-year-old girl who is the first child of healthy, nonconsanguineous parents. She was born at 38 weeks gestation by Cesarean section because of fetal distress, with a birth weight of 2120 g. WHS was suspected soon after birth because of her craniofacial
features, and was confirmed by chromosomal analysis using the G-band method and fluorescence in situ hybridization. The karyotype was 46,XX,del(4)(p16).ish del(4)(p16)(D4S96-,D4S174þ). She achieved head control at 8 months, sitting at 4 years, and standing with support at 9 years of age after an operation for congenital clubfoot. She underwent surgery for correction of an atrial septal defect at age 2 years and for vesicoureteral reflux causing recurrent urinary tract infections at age 6 years. Bilateral tympanostomy tubes were placed for chronic otitis media at age 6 years. The patient characteristics are listed in the Table. At age 5 months she presented with status epilepticus and fever, and at age 10 months she developed afebrile seizures two to three times daily that required treatment with intravenous diazepam. Treatment with clobazam and valproate reduced the frequency of seizures, but she continued to require hospitalization for status epilepticus when she had fevers. She has been seizure free since age 34 months and continues to take clobazam and valproate because her mother is concerned about further seizures. Brain MRI at age 33 months (Figure B) revealed a reduced volume of white matter. The child can eat solid foods but requires supplementary nasogastric tube feeding for liquids. She cannot understand or speak words and has profoundly autistic behaviors. Her mother reported that listening to music had a calming effect on the patient since infancy. Music therapy based on applied behavioral analysis was introduced at age 5 years. The
FIGURE. (A) Patient 1: normal brain magnetic resonance imaging (MRI) at age 7 years and schematic representation of the deletion of chromosome 4p (crosshatched area). (B) Patient 2: brain MRI at age 33 months depicting a reduced volume of white matter and schematic representation of the deletion of chromosome 4p (cross-hatched area) depicting a larger deletion than in Patient 1.
552
C. Arakawa et al. / Pediatric Neurology 51 (2014) 550e552
music therapist sang improvised songs and played the keyboard, drum, and autoharp. The cabasa and the maraca were also played by rolling the instruments on the child’s body. Sometimes the music was played slower and slower to induce a response from the patient, and sometimes the music was played just after achieving a target behavior. The patient subsequently developed communication skills such as eye contact, joint attention, and vocalizations to request music. At age 9 years, her developmental quotient measured by the Tsumori-Inage mental development test for infants7 was less than 10.
Discussion 8
Battaglia et al. reported a series of 87 patients with WHS, all of whom had global developmental delay. In their series, 45% of patients could walk either independently or with support, and 18% could help with dressing and undressing themselves. Recent reports identified patients with milder developmental delay than previously expected, but patients with WHS usually have a very limited ability to communicate.9,10 Sabbadini et al.9 evaluated the communion skills of 11 patients with WHS and found that only one patient used verbal expression, and the nonverbal communication skills of all patients were limited to expressing basic needs. Borsel et al.10 reported a 10-year-old girl with WHS who was able to communicate with speech and suggested that this ability was related to a smaller chromosome 4p deletion than in other patients with WHS. Neither of the patients described in the present report can speak words, but both have a strong affinity for music. Improvisational music therapy is widely used for the treatment of children with autism and is gaining growing recognition as an effective intervention for improving spontaneous self-expression, emotional communication, and social engagement in individuals with a wide range of developmental disorders.11 Increased musical interest and ability has been reported in patients with Williams syndrome (WS), which results from deletion of the long arm of chromosome 7.12,13 WS has a much higher incidence (1 of 7500)14 than WHS (1 of 20,000-1 of 50,000)8 and has therefore been more widely studied. The results of a functional MRI study suggest an association between increased activation of the right amygdala and musical sensitivity in patients with WS.12 Martens et al.13 studied 38 patients with WS and suggested that musical experience enhanced verbal memory. The ability of Patient 1 to hum many tunes, including at least one that she had heard only once, suggests that she may be an example of the so-called “savant syndrome,” which is a rare condition in which persons with serious mental disabilities have some “island of genius” that stands in marked, incongruous contrast to the overall handicap, such as musical, artistic, calendar calculating, mathematical, mechanical, or spatial skills.15 Previous studies have described the developmental findings in patients with WHS and suggested various
rehabilitation therapies, but there is no standard recommendation for therapy to improve the communication skills in these patients. Music therapy has not been suggested for patients with WHS. The findings in our two patients suggest that some patients with WHS may have an affinity for music and may benefit from music therapy. Additional individuals need to be studied to investigate the relationship between interest in music and WHS. Written informed consent for the publication of the patient details including images was obtained from the parents of both patients.
References 1. Cooper H, Hirschhorn K. Apparent deletion of short arms of one chromosome (4 or 5) in a child with defects of midline fusion. Mammalian Chrom Nwsl. 1961;4:14. 2. Battaglia A, Carey JC, Wright TJ. Wolf-Hirschhorn (4p-) syndrome. Adv Pediatr. 2001;48:75-113. 3. Bergemann AD, Cole F, Hirschhorn K. The etiology of WolfHirschhorn syndrome. Trends Genet. 2005;21:188-195. 4. Zollino M, Lecce R, Fischetto R, et al. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2. Am J Hum Genet. 2003;72:590-597. 5. Zollino M, Murdolo M, Marangi G, et al. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet. 2008;148C:257-269. 6. Koyama T, Osada H, Tsujii H, Kurita H. Utility of the Kyoto Scale of Psychological Development in cognitive assessment of children with pervasive developmental disorders. Psychiatry Clin Neurosci. 2009;63:241-243. 7. Aoyama M, Wei CN, Harada K, Ueda K, Takano M, Ueda A. Community factors to promote parents’ quality of child-nurturing life. Environ Health Prev Med. 2013;18:57-70. 8. Battaglia A, Filippi T, Carey JC. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. Am J Med Genet C Semin Med Genet. 2008;148C:246-251. 9. Sabbadini M, Bombardi P, Carlesimo GA, Rosato V, Pierro MM. Evaluation of communicative and functional abilities in WolfHirschhorn syndrome. J Intellect Disabil Res. 2002;46(Pt 7): 575-582. 10. Van Borsel J, De Grande S, Van Buggenhout G, Fryns JP. Speech and language in Wolf-Hirschhorn syndrome: a case-study. J Commun Disord. 2004;37:21-33. 11. Kim J, Wigram T, Gold C. Emotional, motivational and interpersonal responsiveness of children with autism in improvisational music therapy. Autism. 2009;13:389-409. 12. Levitin DJ. Musical behavior in a neurogenetic developmental disorder: evidence from Williams Syndrome. Ann N Y Acad Sci. 2005; 1060:325-334. 13. Martens MA, Jungers MK, Steele AL. Effect of musical experience on verbal memory in Williams syndrome: evidence from a novel word learning task. Neuropsychologia. 2011;49:3093-3102. 14. Strømme P, Bjørnstad PG, Ramstad K. Prevalence estimation of Williams syndrome. J Child Neurol. 2002;17:269-271. 15. Treffert DA. The savant syndrome: an extraordinary condition. A synopsis: past, present, future. Philos Trans R Soc Lond B Biol Sci. 2009;364:1351-1357.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Affinity for Music in Wolf-Hirschhorn Syndrome: Two Case Reports Chikako Arakawa MD a, Yukihiko Fujita MD, PhD b, Tatsuo Fuchigami MD, PhD a, *, Yuki Kawamura MD a, Wakako Ishii MD a, Ayumi Endo MD, PhD a, Ryutaro Kohira MD, PhD a, Shori Takahashi MD, PhD a a b
Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan Division of Medical Education Planning, Nihon University School of Medicine, Tokyo, Japan
abstract BACKGROUND: Wolf-Hirschhorn syndrome is a congenital malformation syndrome resulting from deletion of the short arm of chromosome 4. Individuals with Wolf-Hirschhorn syndrome may have a “Greek warrior helmet” appearance, growth retardation, developmental delay, muscular hypotonia, epilepsy, and difficulty with language including verbal communication. An affinity for music has not previously been reported in these patients. PATIENTS: We describe two patients with Wolf-Hirschhorn syndrome who both have a strong affinity for music. One patient is a 20-year-old woman who likes to listen to music all day and can hum many tunes. The other patient is a 9-year-old girl who is calmed by music and received music therapy, with subsequent improvement in her communication skills (eye contact, joint attention, and vocalizations to request music). CONCLUSIONS: Individuals with Wolf-Hirschhorn syndrome may have a strong affinity for music and may benefit from music therapy. Additional studies are needed to investigate the interest in music in individuals with Wolf-Hirschhorn syndrome. Keywords: Wolf-Hirschhorn syndrome, chromosomal disorder, music, music therapy, communication skills
Pediatr Neurol 2014; 51: 550-552 Ó 2014 Elsevier Inc. All rights reserved.
Introduction
Patient Descriptions
Wolf-Hirschhorn syndrome (WHS) is a congenital malformation pattern resulting from deletion of the short arm of chromosome 4, which was first described by Cooper and Hirschhorn in 1961.1 Individuals with WHS have a variable phenotype and may present with abnormalities such as a “Greek warrior helmet” appearance, growth retardation, developmental delay, muscular hypotonia, and epilepsy. The size of the chromosome 4p deletion is highly variable,2-5 but the correlation between deletion size and phenotype remains unclear. We present two patients with WHS who have a strong affinity for music, which has not previously been reported.
Patient 1
Article History: Received April 23, 2014; Accepted in final form July 9, 2014 * Communications should be addressed to: Dr. Fuchigami; Department of Pediatrics and Child Health; Nihon University School of Medicine; 30-1 Oyaguchi-Kamicho; Itabashi-ku, Tokyo 173-8610, Japan. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.07.012
This 20-year-old woman is the second child of healthy, nonconsanguineous parents. She was born by uncomplicated vaginal delivery at 41 weeks of gestation with a birth weight of 2305 g. She achieved head control at 5 months, sitting at 23 months, and independent walking at 3 years of age. She developed recurrent otitis media with effusion during her childhood. No major organ anomalies were detected. The patient characteristics are listed in the Table. She presented with status epilepticus with fever at age 9 months and subsequently developed simple and/or complex partial seizures up to eight times daily, triggered by fever or bathing. Zonisamide therapy was tried initially but did not control the seizures, and her medications were changed to carbamazepine, valproate, and clonazepam. The seizures decreased in frequency to two to three times per year at age 4 years and stopped at age 13 years. She continues to take the same three antiepileptic medications. At 7 years of age, brain magnetic resonance imaging (MRI) was normal (Figure A), and chromosomal analysis using fluorescence in situ hybridization revealed a karyotype of 46,XX.ish del(4)(p16.3p16.3)(D4S96).
C. Arakawa et al. / Pediatric Neurology 51 (2014) 550e552
551
TABLE. Characteristics of Two Patients With Wolf-Hirschhorn Syndrome
Characteristics
Age (yr)
4p Deletion Location
Gestation, Birth Weight
Major Dysfunction
Age at First Seizure
Seizure Triggers
Admissions for Seizures
Age at Last Seizure
Patient 1
20
4p16.3
41 wk, 2305 g (2.2 SD)
Otitis media, eating difficulty
9 month
Fever, bathing
1
13 year
Patient 2
9
4p16
38 wk, 2120 g (1.9 SD)
Atrial septal defect, vesicoureteral reflux, clubfoot, otitis media, eating difficulty
5 month
Fever
6
34 month
Abbreviation: SD ¼ Standard deviation
At age 18 years of age, her intelligence score on the Tanaka-Binet test (the Japanese version of the Stanford-Binet intelligence test)6 was 17. Since leaving high school, she has worked at facilities that provide employment for handicapped people. She can eat solids and thickened liquids, but cannot swallow water. She understands a few simple words such as “stop” and “come,” but does not speak any words. Her mother first reported an affinity for music at age 2 years 3 months, during the patient’s first admission to our hospital. She likes to hum and listen to music all day, and if the music stops, she pinches her mother to indicate that she wants it to restart. She appears to enjoy humming and hums seasonal tunes at Christmas time. Her mother reported that the patient can hum over 100 tunes and that she learned to hum a tune that her teacher had improvised and played only once in the classroom. It therefore seems that she can remember and hum some tunes after hearing them only once. The patient has not participated in music therapy. She continues to live at home with her family.
Patient 2 This is a 9-year-old girl who is the first child of healthy, nonconsanguineous parents. She was born at 38 weeks gestation by Cesarean section because of fetal distress, with a birth weight of 2120 g. WHS was suspected soon after birth because of her craniofacial
features, and was confirmed by chromosomal analysis using the G-band method and fluorescence in situ hybridization. The karyotype was 46,XX,del(4)(p16).ish del(4)(p16)(D4S96-,D4S174þ). She achieved head control at 8 months, sitting at 4 years, and standing with support at 9 years of age after an operation for congenital clubfoot. She underwent surgery for correction of an atrial septal defect at age 2 years and for vesicoureteral reflux causing recurrent urinary tract infections at age 6 years. Bilateral tympanostomy tubes were placed for chronic otitis media at age 6 years. The patient characteristics are listed in the Table. At age 5 months she presented with status epilepticus and fever, and at age 10 months she developed afebrile seizures two to three times daily that required treatment with intravenous diazepam. Treatment with clobazam and valproate reduced the frequency of seizures, but she continued to require hospitalization for status epilepticus when she had fevers. She has been seizure free since age 34 months and continues to take clobazam and valproate because her mother is concerned about further seizures. Brain MRI at age 33 months (Figure B) revealed a reduced volume of white matter. The child can eat solid foods but requires supplementary nasogastric tube feeding for liquids. She cannot understand or speak words and has profoundly autistic behaviors. Her mother reported that listening to music had a calming effect on the patient since infancy. Music therapy based on applied behavioral analysis was introduced at age 5 years. The
FIGURE. (A) Patient 1: normal brain magnetic resonance imaging (MRI) at age 7 years and schematic representation of the deletion of chromosome 4p (crosshatched area). (B) Patient 2: brain MRI at age 33 months depicting a reduced volume of white matter and schematic representation of the deletion of chromosome 4p (cross-hatched area) depicting a larger deletion than in Patient 1.
552
C. Arakawa et al. / Pediatric Neurology 51 (2014) 550e552
music therapist sang improvised songs and played the keyboard, drum, and autoharp. The cabasa and the maraca were also played by rolling the instruments on the child’s body. Sometimes the music was played slower and slower to induce a response from the patient, and sometimes the music was played just after achieving a target behavior. The patient subsequently developed communication skills such as eye contact, joint attention, and vocalizations to request music. At age 9 years, her developmental quotient measured by the Tsumori-Inage mental development test for infants7 was less than 10.
Discussion 8
Battaglia et al. reported a series of 87 patients with WHS, all of whom had global developmental delay. In their series, 45% of patients could walk either independently or with support, and 18% could help with dressing and undressing themselves. Recent reports identified patients with milder developmental delay than previously expected, but patients with WHS usually have a very limited ability to communicate.9,10 Sabbadini et al.9 evaluated the communion skills of 11 patients with WHS and found that only one patient used verbal expression, and the nonverbal communication skills of all patients were limited to expressing basic needs. Borsel et al.10 reported a 10-year-old girl with WHS who was able to communicate with speech and suggested that this ability was related to a smaller chromosome 4p deletion than in other patients with WHS. Neither of the patients described in the present report can speak words, but both have a strong affinity for music. Improvisational music therapy is widely used for the treatment of children with autism and is gaining growing recognition as an effective intervention for improving spontaneous self-expression, emotional communication, and social engagement in individuals with a wide range of developmental disorders.11 Increased musical interest and ability has been reported in patients with Williams syndrome (WS), which results from deletion of the long arm of chromosome 7.12,13 WS has a much higher incidence (1 of 7500)14 than WHS (1 of 20,000-1 of 50,000)8 and has therefore been more widely studied. The results of a functional MRI study suggest an association between increased activation of the right amygdala and musical sensitivity in patients with WS.12 Martens et al.13 studied 38 patients with WS and suggested that musical experience enhanced verbal memory. The ability of Patient 1 to hum many tunes, including at least one that she had heard only once, suggests that she may be an example of the so-called “savant syndrome,” which is a rare condition in which persons with serious mental disabilities have some “island of genius” that stands in marked, incongruous contrast to the overall handicap, such as musical, artistic, calendar calculating, mathematical, mechanical, or spatial skills.15 Previous studies have described the developmental findings in patients with WHS and suggested various
rehabilitation therapies, but there is no standard recommendation for therapy to improve the communication skills in these patients. Music therapy has not been suggested for patients with WHS. The findings in our two patients suggest that some patients with WHS may have an affinity for music and may benefit from music therapy. Additional individuals need to be studied to investigate the relationship between interest in music and WHS. Written informed consent for the publication of the patient details including images was obtained from the parents of both patients.
References 1. Cooper H, Hirschhorn K. Apparent deletion of short arms of one chromosome (4 or 5) in a child with defects of midline fusion. Mammalian Chrom Nwsl. 1961;4:14. 2. Battaglia A, Carey JC, Wright TJ. Wolf-Hirschhorn (4p-) syndrome. Adv Pediatr. 2001;48:75-113. 3. Bergemann AD, Cole F, Hirschhorn K. The etiology of WolfHirschhorn syndrome. Trends Genet. 2005;21:188-195. 4. Zollino M, Lecce R, Fischetto R, et al. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2. Am J Hum Genet. 2003;72:590-597. 5. Zollino M, Murdolo M, Marangi G, et al. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet. 2008;148C:257-269. 6. Koyama T, Osada H, Tsujii H, Kurita H. Utility of the Kyoto Scale of Psychological Development in cognitive assessment of children with pervasive developmental disorders. Psychiatry Clin Neurosci. 2009;63:241-243. 7. Aoyama M, Wei CN, Harada K, Ueda K, Takano M, Ueda A. Community factors to promote parents’ quality of child-nurturing life. Environ Health Prev Med. 2013;18:57-70. 8. Battaglia A, Filippi T, Carey JC. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. Am J Med Genet C Semin Med Genet. 2008;148C:246-251. 9. Sabbadini M, Bombardi P, Carlesimo GA, Rosato V, Pierro MM. Evaluation of communicative and functional abilities in WolfHirschhorn syndrome. J Intellect Disabil Res. 2002;46(Pt 7): 575-582. 10. Van Borsel J, De Grande S, Van Buggenhout G, Fryns JP. Speech and language in Wolf-Hirschhorn syndrome: a case-study. J Commun Disord. 2004;37:21-33. 11. Kim J, Wigram T, Gold C. Emotional, motivational and interpersonal responsiveness of children with autism in improvisational music therapy. Autism. 2009;13:389-409. 12. Levitin DJ. Musical behavior in a neurogenetic developmental disorder: evidence from Williams Syndrome. Ann N Y Acad Sci. 2005; 1060:325-334. 13. Martens MA, Jungers MK, Steele AL. Effect of musical experience on verbal memory in Williams syndrome: evidence from a novel word learning task. Neuropsychologia. 2011;49:3093-3102. 14. Strømme P, Bjørnstad PG, Ramstad K. Prevalence estimation of Williams syndrome. J Child Neurol. 2002;17:269-271. 15. Treffert DA. The savant syndrome: an extraordinary condition. A synopsis: past, present, future. Philos Trans R Soc Lond B Biol Sci. 2009;364:1351-1357.