Interview with Robert Shprintzen, Ph.D.
Share:
Beck:Hi Dr. Shprintzen, it's a pleasure to speak with you.Shprintzen: Hi. Dr. Beck, the pleasure is mine.Beck:If you don't mind, before we address velo-cardial-facial (VCF) syndrome, would you please tell me a little about your professional education?Shprintzen:Certainly. I earned my doctorate from
Beck:Hi Dr. Shprintzen, it's a pleasure to speak with you.
Shprintzen: Hi. Dr. Beck, the pleasure is mine.
Beck:If you don't mind, before we address velo-cardial-facial (VCF) syndrome, would you please tell me a little about your professional education?
Shprintzen:Certainly. I earned my doctorate from Syracuse University in 1973. My degree was in Speech Pathology, but I focused on physiology at the time, and in particular, my research was in videofluoroscopy, which we used to assess velopharyngeal function.
Beck:You must've worked with the pioneers in the field at that time?
Shprintzen:Yes. I worked with Dr. Leon Skolnick, he pretty much invented the whole process.
Beck:Very good. And over the last few years, I suspect you've been mostly at medical centers?
Shprintzen:Yes. I was the director of the craniofacial center at Montefiore Medical Center in the Bronx. I was there for 23 years. I'm currently Professor of Otolaryngology, and Professor of Pediatrics and I run the Communication Disorders Unit at Upstate Medical University in Syracuse, within the Statue University of New York (SUNY) system.
Beck:Excellent. Please tell me, what is Velo-Cardio-Facial (VCFS) Syndrome?
Shprintzen:VCFS has a number of different names and that tends to confuse things. One of my mentors said geneticists are more likely to share their toothbrush than their terminology -- and that's what's happened. Some people call VCFS "DiGeorge Syndrome" named after the endocrinologist in Philadelphia. It's also called "Sedlackova Syndrome," which was described in 1955, and that's probably the earliest description of the disorder. The other name one hears is the 22Q11 Deletion Syndrome because the disorder is caused by a deletion from the long arm of chromosome 22, but generally, in the USA, we call it VCFS.
Beck:Where did the name "VCFS" come from?
Shprintzen:In 1978, I was actually the person that coined the term "VCFS" in a publication I was working on. The findings we emphasized consisted of cleft palate or submucous cleft palate in the presence of congenital heart disease, learning disability and a characteristic facial appearance. At that time, things were named by their clinical findings or characteristics, hence the name, VCFS.
Beck:Are cleft palate and cleft lip equally represented in VCFS?
Shprintzen:No. Cleft lip is actually fairly rare in this population. The overwhelming majority of the cases are cleft palate or submucous cleft. In fact, some 5 to 8 percent of all children with hypernasal speech and/or cleft palate have VCFS.
Beck:Please clarify for me...what are the cardiac abnormalities associated with VCFS?
Shprintzen:The cardiac anomalies are known as conotruncal anomalies, and there are a few different presentations of these in VCFS. The important thing for the SLP, is when a child has feeding problems and cardiac disorders, the chance of having VCF is pretty high.
Beck:Which learning disabilities are the most common in VCFS children?
Shprintzen:They vary. There's an enormous amount of ongoing research in brain imaging and brain functioning in these kids through the NIH, and so in a few years, we'll have better answers. At this time we know these children often have reduced brain volume and the disorders are usually within areas such as problem solving, executive functioning, reading comprehension and mathematical concepts. In the early years, the children have fairly robust learning skills, but as they get more and more challenged via math and reading comprehension, the difficulty becomes more pronounced.
Beck:With regard to the facial presentation...what is the most typical presentation?
Shprintzen:They have a generalized hypotyonia and their faces look longer than normal. Ears are generally smaller with over-folded helices and their noses are typically prominent. So the faces have VCFS characteristics, but they don't generally look significantly abnormal. With regard to facial characteristics, it's not like Down Syndrome, which is easier to recognize. VCFS children look pretty normal, although they share some common characteristics.
Beck:Is VCFS an autosomal dominant disorder?
Shprintzen:Yes. It's inherited as an autosomal dominant, but it's called a microdeletion syndrome, also called a contiguous gene syndrome, caused by a deletion of some 3 million base pairs of DNA from one copy of chromosome 22. The region of deletion has some 48 genes, and again, that's inherited in a dominant manner, but most cases are new cases from spontaneous mutations because the deleted region is known as a "hot spot" in the human genome.
Beck:And chromosome 22 is the "hottest" of the hot spots?
Shprintzen:Yes, I think so. These disorders are very common in the general population. The population prevalence is 1 per 2000 people.
Beck:And given all of these characteristics and anomalies...who is it that generally makes the diagnosis?
Shprintzen:Good question. VCFS is the most common syndrome of congenital heart disease, and the heart problems are generally noted first. Keep in mind that most of the clefts are submucous clefts, not overt, and so they're not visualized readily. However, only some 75 percent of kids with VCF have clinically detectable heart disease. Sometimes after the onset of speech, hypernasality is noted, and when explored, a submucous cleft is detected, and that can lead to the diagnosis, too, at age 2, 3 or 4 years.
Beck:And I believe there is a psychiatric component to the VCFS syndrome?
Shprintzen:Exactly right. We published a paper in 1992 that showed a high frequency of psychiatric illness in these children, and there has been a lot of interest in that area since that time. So some children are diagnosed later in life, based on their psychiatric issues, and the most common psychiatric presentation is ADD/ADHD.
Beck:How does one actually confirm the VCFS diagnosis?
Shprintzen:The test used is called Fluorescent in-situ hybridization (FISH). FISH is a highly reliable and relatively simple molecular genetics test. It's usually a few hundred dollars and is usually covered by insurance, and it's usually detected at birth, secondary to their heart problems.
Beck:And finally, what are the treatment options?
Shprintzen:They're as different as the syndrome presentation itself, and we have found 188 manifestations of VCFS, with significant variability from very mild, to extreme. There are no obligatory findings in VCFS, and likewise, nobody has all 188 findings. So treatment is vast and varied, depending on the presentation.
Beck:This has been fascinating, thank you very much for your time and knowledge.
Shprintzen:My pleasure, thanks for the opportunity to address the www.speechpathology.com audience. For people who need more information on VCFS, or for those aware of a 16 year old (or older) VCFS patient who might be interested in participating in a study or even a clinical trial, please write to me at shprintr@upstate.edu. Also, I must recommend a web site and organization for people who want access to expert information. It is The Velo-Cardio-Facial Syndrome Educational Foundation, Inc. and the web site is www.vcfsef.org.
Shprintzen: Hi. Dr. Beck, the pleasure is mine.
Beck:If you don't mind, before we address velo-cardial-facial (VCF) syndrome, would you please tell me a little about your professional education?
Shprintzen:Certainly. I earned my doctorate from Syracuse University in 1973. My degree was in Speech Pathology, but I focused on physiology at the time, and in particular, my research was in videofluoroscopy, which we used to assess velopharyngeal function.
Beck:You must've worked with the pioneers in the field at that time?
Shprintzen:Yes. I worked with Dr. Leon Skolnick, he pretty much invented the whole process.
Beck:Very good. And over the last few years, I suspect you've been mostly at medical centers?
Shprintzen:Yes. I was the director of the craniofacial center at Montefiore Medical Center in the Bronx. I was there for 23 years. I'm currently Professor of Otolaryngology, and Professor of Pediatrics and I run the Communication Disorders Unit at Upstate Medical University in Syracuse, within the Statue University of New York (SUNY) system.
Beck:Excellent. Please tell me, what is Velo-Cardio-Facial (VCFS) Syndrome?
Shprintzen:VCFS has a number of different names and that tends to confuse things. One of my mentors said geneticists are more likely to share their toothbrush than their terminology -- and that's what's happened. Some people call VCFS "DiGeorge Syndrome" named after the endocrinologist in Philadelphia. It's also called "Sedlackova Syndrome," which was described in 1955, and that's probably the earliest description of the disorder. The other name one hears is the 22Q11 Deletion Syndrome because the disorder is caused by a deletion from the long arm of chromosome 22, but generally, in the USA, we call it VCFS.
Beck:Where did the name "VCFS" come from?
Shprintzen:In 1978, I was actually the person that coined the term "VCFS" in a publication I was working on. The findings we emphasized consisted of cleft palate or submucous cleft palate in the presence of congenital heart disease, learning disability and a characteristic facial appearance. At that time, things were named by their clinical findings or characteristics, hence the name, VCFS.
Beck:Are cleft palate and cleft lip equally represented in VCFS?
Shprintzen:No. Cleft lip is actually fairly rare in this population. The overwhelming majority of the cases are cleft palate or submucous cleft. In fact, some 5 to 8 percent of all children with hypernasal speech and/or cleft palate have VCFS.
Beck:Please clarify for me...what are the cardiac abnormalities associated with VCFS?
Shprintzen:The cardiac anomalies are known as conotruncal anomalies, and there are a few different presentations of these in VCFS. The important thing for the SLP, is when a child has feeding problems and cardiac disorders, the chance of having VCF is pretty high.
Beck:Which learning disabilities are the most common in VCFS children?
Shprintzen:They vary. There's an enormous amount of ongoing research in brain imaging and brain functioning in these kids through the NIH, and so in a few years, we'll have better answers. At this time we know these children often have reduced brain volume and the disorders are usually within areas such as problem solving, executive functioning, reading comprehension and mathematical concepts. In the early years, the children have fairly robust learning skills, but as they get more and more challenged via math and reading comprehension, the difficulty becomes more pronounced.
Beck:With regard to the facial presentation...what is the most typical presentation?
Shprintzen:They have a generalized hypotyonia and their faces look longer than normal. Ears are generally smaller with over-folded helices and their noses are typically prominent. So the faces have VCFS characteristics, but they don't generally look significantly abnormal. With regard to facial characteristics, it's not like Down Syndrome, which is easier to recognize. VCFS children look pretty normal, although they share some common characteristics.
Beck:Is VCFS an autosomal dominant disorder?
Shprintzen:Yes. It's inherited as an autosomal dominant, but it's called a microdeletion syndrome, also called a contiguous gene syndrome, caused by a deletion of some 3 million base pairs of DNA from one copy of chromosome 22. The region of deletion has some 48 genes, and again, that's inherited in a dominant manner, but most cases are new cases from spontaneous mutations because the deleted region is known as a "hot spot" in the human genome.
Beck:And chromosome 22 is the "hottest" of the hot spots?
Shprintzen:Yes, I think so. These disorders are very common in the general population. The population prevalence is 1 per 2000 people.
Beck:And given all of these characteristics and anomalies...who is it that generally makes the diagnosis?
Shprintzen:Good question. VCFS is the most common syndrome of congenital heart disease, and the heart problems are generally noted first. Keep in mind that most of the clefts are submucous clefts, not overt, and so they're not visualized readily. However, only some 75 percent of kids with VCF have clinically detectable heart disease. Sometimes after the onset of speech, hypernasality is noted, and when explored, a submucous cleft is detected, and that can lead to the diagnosis, too, at age 2, 3 or 4 years.
Beck:And I believe there is a psychiatric component to the VCFS syndrome?
Shprintzen:Exactly right. We published a paper in 1992 that showed a high frequency of psychiatric illness in these children, and there has been a lot of interest in that area since that time. So some children are diagnosed later in life, based on their psychiatric issues, and the most common psychiatric presentation is ADD/ADHD.
Beck:How does one actually confirm the VCFS diagnosis?
Shprintzen:The test used is called Fluorescent in-situ hybridization (FISH). FISH is a highly reliable and relatively simple molecular genetics test. It's usually a few hundred dollars and is usually covered by insurance, and it's usually detected at birth, secondary to their heart problems.
Beck:And finally, what are the treatment options?
Shprintzen:They're as different as the syndrome presentation itself, and we have found 188 manifestations of VCFS, with significant variability from very mild, to extreme. There are no obligatory findings in VCFS, and likewise, nobody has all 188 findings. So treatment is vast and varied, depending on the presentation.
Beck:This has been fascinating, thank you very much for your time and knowledge.
Shprintzen:My pleasure, thanks for the opportunity to address the www.speechpathology.com audience. For people who need more information on VCFS, or for those aware of a 16 year old (or older) VCFS patient who might be interested in participating in a study or even a clinical trial, please write to me at shprintr@upstate.edu. Also, I must recommend a web site and organization for people who want access to expert information. It is The Velo-Cardio-Facial Syndrome Educational Foundation, Inc. and the web site is www.vcfsef.org.