Today’s guest post on genetic syndromes comes from Lauren Laur, who is contributing a post on the 22q11.2 Deletion Syndrome.
22q11.2 Deletion Syndrome is a syndrome of many names. Also known as Velocardiofacial Syndrome, Shprintzen syndrome as well as DiGeorge Syndrome, 22q11.2 Deletion Syndromeis is caused by a microdeletion on the long arm of chromosome 22 (at location marker q11.2). This syndrome follows an autosomal dominant inheritance pattern (a child only needs to get the abnormal gene from one parent in order to inherit the disease), however, only around 10% of cases are inherited; the majority of cases are due to a random mutation.
The characteristics of 22q Deletion Syndrome include congenital heart defects, palate abnormalities, velopharyngeal dysfunction, hearing loss, decreased immune system, learning disabilities, feeding difficulties, gastrointestinal problems, and emotional as well as psychiatric difficulties.
It is estimated that 22q Deletion Syndrome occurs in 1 out of 4,000 live births. This may underestimate its true prevalence, as children with mild symptoms of the syndrome may go undiagnosed. It is further estimated that 22q Deletion Syndrome occurs in 1 out of 68 children that have a congenital heart defect and in 5-8% of children that have a cleft palate. 22q Deletion Syndrome is the second most common multi-anomaly genetic disorder after Down syndrome.
It is important to note that if a child’s symptoms are mild, 22q Deletion Syndrome may be misdiagnosed as isolated speech/language disorder or developmental delays. There are over 80 different characteristics of 22q Deletion Syndrome, so presentations vary greatly in different children. This large variation can make diagnosis more difficult. Some children are not diagnosed until they are in elementary school. According to some research, the median age of diagnosis is 6.5 years. Children with mild presentations of 22q Deletion Syndrome are typically diagnosed through cardiology, immunology, and cleft palate clnics. SLPs can play an important role in the diagnosis of 22q Deletion Syndrome because velopharyngeal dysfunction or cleft palate may bring families to a cleft palate clinic before a diagnosis of 22q Deletion Syndrome is suspected. 22q Deletion Syndrome is diagnosed through fluorescent in situ hybridization (FISH) studies, which is specially designed to look for small groups of genes that are deleted.
Current research suggests that males with 22q Deletion Syndrome typically have more severe cognitive deficits than females. There do not appear to be significant differences in other aspects of 22q Deletion Syndrome in males and females.
The physical features associated with 22q Deletion Syndrome include the following: hooded eyelids, thin upper lip, wide nose bridge, a bulbous tip of the nose, and small ears with squared tops. Individuals with 22q Deletion Syndrome may also have growth problems or restrictions.
22q Deletion Syndrome can cause a variety of different medical complications and may affect almost all systems of the body. One of the most frequently occurring medical complications for children with 22q Deletion Syndrome is a congenital heart defect. It is estimated that 70-80% of children with 22q Deletion Syndrome have some type of cardiac abnormality. The most frequently occurring cardiac problems include tetralogy of Fallot, interrupted aortic arch, ventricular septal defect (VSD), vascular ring, and truncus arteriosus. In addition, the majority of children with 22q Deletion Syndrome have some type of palatal abnormality or velopharyngeal dysfunction. It is more common for a child with 22q Deletion Syndrome to have a submucous cleft as opposed to an overt cleft palate. Velopharyngeal dysfunction occurs in 75-80% of children with 22q.
Children with 22q Deletion Syndrome may also have low levels of calcium in their blood, which is called hypocalcemia. This is typically due to problems with the parathyroid gland and may trigger seizures. Children with 22q Deletion Syndrome may also have chronic middle ear infections or hearing loss. The degree of hearing loss can vary, depending on the presentation of the syndrome.
Approximately 30-35% of children with 22q Deletion Syndrome have kidney problems. This may include having a malformed kidney or missing a kidney.
Many children with 22q Deletion Syndrome have immune deficiency and suffer from frequent infections such as recurrent ear infections, sinusitis, and respiratory infections.
A large number of children suffer from gastrointestinal problems that most frequently include gastroesophageal reflux (GERD) and constipation.
Many children with 22q Deletion Syndrome exhibit behavioral or psychiatric problems. Children with 22q Deletion Syndrome are likely to have poor attention and many meet criteria to be diagnosed with ADD or ADHD. In addition, children with 22q Deletion Syndrome are much more likely to be diagnosed with a serious mental illness sometime in their lifetime than individuals without the syndrome. Some research estimates that as many as 25% of individuals with 22q Deletion Syndrome develop mental illness in adulthood. The most common mental illnesses are depression, anxiety disorders, obsessive-compulsive disorder, or schizophrenia. A high percentage of children with 22q Deletion Syndrome meet the criteria for an Autism Spectrum Disorder as well.
Children with 22q Deletion Syndrome typically have some degree of cognitive impairment, but cognitive functioning varies widely across children with 22q Deletion Syndrome. The average IQ of children with 22q Deletion Syndrome is between 70-80. Children who have inherited 22q Deletion Syndrome from a parent typically have lower cognitive abilities than children who have acquired 22q Deletion Syndrome due to a random genetic mutation. In general, the areas of vocabulary, reading skills, and rote recall of facts are relative strengths for children with 22q Deletion Syndrome. Mathematical skills and visual-spatial skills are often relative weaknesses.
Speech and Language Issues and Applicable Interventions
There are many different speech and language problems that are associated with 22q Deletion syndrome. It is estimated that over 90% of children with 22q Deletion Syndrome have some type of speech-language impairment. Children with this syndrome may have feeding difficulties, velopharyngeal dysfunction, articulation disorders, language disorders, voice disorders, and pragmatic language delays.
The majority of individuals with 22q Deletion Syndrome exhibit feeding and swallowing problems in infancy. The degree and type of feeding difficulties vary widely across children. Some feeding difficulties are caused by a cleft palate or other forms of velophyngeal dysfunction. In rare cases, children with 22q Deletion Syndrome may present with Pierre Robin sequence, which can cause airway obstruction and extensive feeding difficulties. Feeding difficulties are more commonly due to gastroesophageal reflux, or other malformations of the GI tract.
Velopharyngeal dysfunction (VPD) occurs in approximately 75-80% of children with 22q Deletion Syndrome. VPD may be caused by an overt cleft palate, but is more commonly the result of a submucous cleft palate or abnormalities in the muscles of the pharynx and soft palate. These abnormalities may include atypical placement of the levator veli palatini muscle or hypoplasia and hypotonia of the levator veli palatini and/or pharyngeal constrictors. In addition, children may have cranial nerve abnormalities that lead to limited or asymmetric closure of the velpharyngeal port. It’s also possible that children with 22q Deletion Syndrome will present with abnormal timing of VP closure. It is fairly rare for a child with 22q Deletion Syndrome to have a cleft lip. For children with a mild presentation of medical complications, VPD may be the first symptom that causes parents to seek professional help. Therefore, it’s important for SLPs to recognize all the symptoms of 22q Deletion Syndrome.
Even when VPD is not present, most children with 22q Deletion Syndrome have a small phonetic inventory and use a restricted variety of speech sounds. When VPD is present, children with 22q Deletion Syndrome are likely to use glottal stop substitutions and exhibit audible nasal emission. Children with 22q Deletion Syndrome are more likely to use glottal stop substitutions than children with non-syndromic cleft palates. Children with 22q Deletion Syndrome are more likely to have characteristics of apraxia than non-syndromic children and children with a non-syndromic cleft palate.
In addition to VPD, some children with 22q Deletion Syndrome also have voice disorders. Children with 22q Deletion Syndrome may have high-pitched voices with reduced loudness. They also could have a hoarse or breathy vocal quality. In rare instances, a child’s hoarse or breathy voice quality may mask VPD and make diagnosis more difficult. It’s also possible for children with 22q Deletion Syndrome to have vocal fold paralysis or paresis.
Approximately 90% of children with 22q Deletion Syndrome exhibit language delays by early elementary school. Many children are late talkers and have few words at 2 years of age. Preschool aged children with 22q Deletion Syndrome often have a reduced vocabulary size, reduced sentence length, and delayed use of grammar structures. Older children tend to have difficulty with figurative language and abstract concepts. They also often have pragmatic language delays, which may include poor interpretation of non-verbal cues as well as poor initiation and reciprocity with peers. In addition, many children with 22q Deletion Syndrome have delayed play skills and reduced emotional expression. For most children with 22q Deletion Syndrome, expressive language delays are more severe than receptive language delays.
It’s important to refer children to a cleft palate team at the time of diagnosis because of the high instance of submucous cleft palate or VPD without the presence of a cleft. Many large hospitals have developed 22q Deletion Syndrome teams. These teams and clinics specifically for children with 22q Deletion Syndrome are becoming more common and easier for families to access as more teams form around the country.
The most common surgical treatments for children that have VPD include a pharyngeal flap or sphincter pharyngoplasty. Some research studies have shown that children with 22q Deletion Syndrome are more likely to have VPD and compensatory articulation errors that persist after surgery than children with a non-syndromic cleft palate. If compensatory errors, such as glottal stop substitutions are present, it’s important to address these errors first in therapy.
When providing speech therapy to young children with a cleft palate or VPD, it’s important to blend intervention approaches to target speech production and facilitate language development. Research has shown that blowing exercises and other non-speech oral motor exercises are not effective for children with 22q Deletion Syndrome. Speech therapy should follow the motor learning approach.
The principles of a motor learning approach include determining whether treatment will be mass (less frequent, longer sessions) or distributed (shorter, more frequent sessions), determining whether practice of a target will be blocked or random, and determining the optimal level of feedback to provide. In general, children often benefit most from shorter, more frequent therapy sessions because of attention deficits. It is typically best to move from blocked practice to random practice as a child’s ability increases and feedback should move from extrinsic to intrinsic and decrease in frequency. Because rote memory is often a relative strength for children with 22q Deletion Syndrome, it’s important to elicit many repetitions and follow a predictable structure.
It’s helpful to use a multi-sensory approach to speech therapy by providing visual, auditory, and tactile feedback. It’s important to teach children to discriminate between oral sounds and nasal sounds. Biofeedback is often a great way to teach discrimination of oral versus nasal sounds. To provide biofeedback, you can use a See-Scape if one is available. You can also put a dental mirror under a child’s nares and watch for fog to appear on the mirror when nasal emission occurs. Another easy and affordable way to provide biofeedback is to have a child place one end of plastic tube or long straw right inside his/her nostril and the other end of the tubing by his/her ear. When nasal emission occurs, it will be louder and easier for the child to perceive because of the tubing.
Bezuhly et al. (2012) conducted a study involving children with submucous cleft palates. Severty-eight children were involved in the study. Of these children, 23 had a diagnosis of 22q Deletion Syndrome. The study found that children with 22q Deletion Syndrome were less likely to achieve normal resonance on a perceptual speech exam following surgery than non-syndromic patients. In addition, children with 22q Deletion Syndrome were more likely to require revisions and further surgery after the initial repair. The median time until normal resonance was achieved was 150 weeks for children with 22q Deletion Syndrome and only 34 weeks for non-syndromic children.
Fullman and Boyer (2012) reported that using an Enhanced Milieu approach when providing early intervention services may be most beneficial to children with 22q Deletion Syndrome. The Enhanced Milieu approach encourages parents, caregivers, and therapists to manipulate the environment in a way that facilitates verbal communication. This approach provides social interactions in contexts that are structured and predicable. Fullman and Boyer recommended combining an Enhanced Milieu approach with a Focused Stimulation approach to improve speech production. In a Focused Stimulation approach, caregivers model specific words many times during play interactions. When a child produces a target word, caregivers offer feedback on the sounds that were produced and expand the child’s utterance.
A multi-disciplinary team should include genetics, cardiology, plastic surgery, speech pathology, dentistry, immunology, psychology, audiology, otolaryngology, endocrinology, hematology, neurology, orthopedics, nephrology, and gastroenterology.
Children with 22q Deletion Syndrome present with complex needs, both medically and in terms of communication. It’s important to involve a multi-disciplinary team so that all of a child’s needs can be addressed. Speech Pathologist may be involved in treating feeding difficulties, velopharyngeal dysfunction, articulation errors, voice disorders, and language delays.
Baylis, Adriane. Presentation entitled “Management of Speech Disorders in Children with 22q11.2 Deletion Syndrome.” Presented at Ninth Annual Cleft Lip/Palate Care Conference. Friday April 26, 2013. St. Louis, MO.
Bezuhly M, Fischbach S, Klaiman P, Fisher DM. (2012). Impact of 22q deletion syndrome on speech outcomes following primary surgery for submucous cleft palate. Plastic and Reconstructive Surgery. 129(3):502e-510e.
Boyer, V. and Fullman, L. Presentation Entitled “ Velo-Cardio-Facial Syndrome: Early Development and Intervention.” Presented at 2012 ASHA Convention.
Fullman, L. and Boyer, V. (2012). Velocardiofacial syndrome and early intervention. Contemporary Issues in Communication Science and Disorders, 39, 21-29.
Nationwide Children’s Hospital. “What is 22q11.2 Deletion Syndrome?”
Peterson-Falzone, SJ et al. (2006). The Clincian’s Guide to Treating Cleft Palate Speech. Mosby Elsevier.
The International 22q11.2 Deletion Syndrome Foundation Inc. “An Overview of 22q.”
University of Rochester Medical Center. “22q11.2 Deletion Syndrome.”
Lauren Laur completed both her undergraduate and graduate degrees at Truman State University in Kirksville, MO. While at Truman, she completed several research projects on early literacy skills, including a thesis related to the language output of preschoolers when reading different genres of books. This is currently her fifth year working for a public school district in mid-Missouri where she primarily works with preschool-aged students in an Early Childhood Special Education program.