22q11.2 deletion syndrome history and symptoms
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] Ayushi Jain, M.B.B.S[3]
Overview
A detailed history and physical is vital in the diagnosis and assessment of DiGeorge syndrome.
History
A broad spectrum of disease severity exists, and suspicion of DGS from history and physical can prompt further evaluation. Although most cases get diagnosed in the prenatal and pediatric periods, diagnosis can also occur in adulthood.
Delay in motor development is a common presenting feature first recognized by parents who notice delays in rolling over, sitting up, or other infant milestones.[1]
These findings can be associated with delayed speech development and learning disabilities. Later in life, abnormal behavior in the setting of poor developmental history may be the chief presenting symptom of DGS.[2]
A detailed history may reveal the following:
- Family history of diagnosed or suspected DGS
- Abnormal genetic testing results of family members
- Delays in the achievement of developmental milestones
- Behavioral disturbance
- Cyanosis, exercise intolerance, or symptoms
- Recurrent infections secondary to T-cell deficiency
- Speech difficulty
- Difficulty feeding and/or failure to thrive
- Muscle spasms, twitching, tetany, seizure
Symptoms
Individuals with a 22q11 deletion can suffer from a range of over 200 possible symptoms, ranging from the mild to the very serious. Possible symptoms are:
- An immune deficiency regardless of their clinical presentation (77%) - recurrent infections
- Significant feeding problems (30%)
- Learning difficulties (70-90%)
- Hearing loss
- Seizures
Presentation
The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a cleft palate or other defect in the palate), autism, other learning disabilities, mild differences in facial features, and recurrent viral or fungal infections are common due to problems with the immune system's T-cell mediated response. DiGeorge syndrome is often first spotted when the affected newborn begins convulsing from hypocalcemia due to an absence of parathyroid and parathyroid hormone. Affected individuals may also have kidney abnormalities, significant feeding difficulties, autoimmune disorders such as rheumatoid arthritis, and an increased risk of developing mental illnesses.[3]
Microdeletions in chromosomal region 22q11 are associated with a roughly 30-fold increased risk of schizophrenia[4] and are frequently detected in schizophrenic patients. Different studies provide different occurrence rates, ranging from 0.5 to 3%, compared with the overall 0.025% risk of the 22q11 deletion syndrome in the general population.[5]
Cognitive and language problems
Cognitive deficits
Children with 22q11.2 have a specific profile in neuropsychological tests. They usually have a low IQ (50-80) but with better verbal than procedural functions. Especially big problems are usually within arithmetic and executive skills. Familial transmission of the disease seems to result in worse cognitive impairments than the de novo cases. It has been speculated that the observed cognitive problems arise from visuo-spatial problems.
Noteworthy is that these patients are a specifically high-risk group for developing schizophrenia. 30% have at least one incident of psychosis and about a quarter develop actual schizophrenia.[6]
Speech and Language
Current research demonstrates there is a unique profile of speech and language impairments associated with 22q11.2 deletion syndrome. Children often perform lower on speech and language evaluations in comparison to their nonverbal IQ scores. Common problems include hypernasality, language delays, and speech sound errors.[7][8][9]
Hypernasality occurs when air escapes through the nose during the production of oral speech sounds resulting in reduced intelligibility. This is a common characteristic in the speech and language profile because 69% of children have palatal abnormalities. If the structure of the soft palate velum is such that it does not stop the flow of air from going up to the nasal cavity, it will cause hypernasal speech. This phenomenon is referred as velopharyngeal inadequacy VPI. Hearing loss can also contribute to increased hypernasality because children with hearing impairments can have difficulty self monitoring their oral speech output. The treatment options available for VPI include prosthesis and surgery. [7] [10][11][8][12]
Difficulties acquiring vocabulary and formulating spoken language (expressive language deficits) at the onset of language development are also part of the speech and language profile associated with the 22q11.2 deletion. Vocabulary acquisition is often severely delayed for preschool age children. In some recent studies, children had a severely limited vocabulary or were still nonverbal at 2-3 years of age. School age children do make progress with expressive language as they mature, but many continue to have delays and demonstrate difficulty when presented with language tasks such as verbally recalling narratives and producing longer and more complex sentences. Receptive language, which is the ability to comprehend, retain, or process spoken language, can also be impaired although not usually with the same severity as expressive language impairments. [13][11][8][12]
Articulation errors are commonly present in children with 22q11.2 deletion syndrome. These errors include a limited phonemic (speech sound) inventory and the use of compensatory articulation strategies resulting in reduced intelligibility. The phonemic inventory typically produced consists of sounds made in the front or back of the vocal tract such as: /p/, /w/, /j/, /m/, /n/, and glottal stops. Mid vocal tract sounds are completely absent. Compensatory articulation errors made by this population of children include: glottal stops, nasal substitutions, pharyngeal fricatives, linguapalatal sibilants, reduced pressure on consonant sounds, or a combination of these symptoms. Of these errors, glottal stops have the highest frequency of occurrence. It is reasoned that a limited phonemic inventory and the use of compensatory articulation strategies is present due to the structural abnormalities of the palate. The speech impairments exhibited by this population are more severe during the younger ages and show a trend of gradual improvement as the child matures. [7][11]
References
- ↑ McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011 Jan;90(1):1-18.
- ↑ McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015 Nov 19;1:15071.
- ↑ Debbané M, Glaser B, David MK, Feinstein C, Eliez S (2006). "Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications". Schizophr. Res. 84 (2–3): 187–93. doi:10.1016/j.schres.2006.01.019. PMID 16545541.
- ↑ Bassett AS, Chow EW, AbdelMalik P, Gheorghiu M, Husted J, Weksberg R (2003). "The schizophrenia phenotype in 22q11 deletion syndrome". Am J Psychiatry. 160 (9): 1580–6. PMID 12944331.
- ↑ Horowitz A, Shifman S, Rivlin N, Pisanté A, Darvasi A (2005). "A survey of the 22q11 microdeletion in a large cohort of schizophrenia patients". Schizophr. Res. 73 (2–3): 263–7. doi:10.1016/j.schres.2004.02.008. PMID 15653270.
- ↑ Zinkstok J, van Amelsvoort T (2005). "Neuropsychological profile and neuroimaging in patients with 22Q11.2 Deletion Syndrome: a review". Child Neuropsychol. 11 (1): 21–37. doi:10.1080/09297040590911194. PMID 15823981.
- ↑ 7.0 7.1 7.2 D'Antonio LL, Scherer NJ, Miller LL, Kalbfleisch JH, Bartley JA (2001). "Analysis of speech characteristics in children with velocardiofacial syndrome (VCFS) and children with phenotypic overlap without VCFS". Cleft Palate Craniofac. J. 38 (5): 455–67. PMID 11522167.
- ↑ 8.0 8.1 8.2 Scherer NJ, D'Antonio LL, Kalbfleisch JH (1999). "Early speech and language development in children with velocardiofacial syndrome". Am. J. Med. Genet. 88 (6): 714–23. PMID 10581495.
- ↑ Scherer NJ, D'Antonio LL, Rodgers JR (2001). "Profiles of communication disorder in children with velocardiofacial syndrome: comparison to children with Down syndrome". Genet. Med. 3 (1): 72–8. PMID 11339384.
- ↑ Eliez S, Palacio-Espasa F, Spira A; et al. (2000). "Young children with Velo-Cardio-Facial syndrome (CATCH-22). Psychological and language phenotypes". Eur Child Adolesc Psychiatry. 9 (2): 109–14. PMID 10926060.
- ↑ 11.0 11.1 11.2 Robin NH, Shprintzen RJ (2005). "Defining the clinical spectrum of deletion 22q11.2". J. Pediatr. 147 (1): 90–6. doi:10.1016/j.jpeds.2005.03.007. PMID 16027702.
- ↑ 12.0 12.1 Solot CB, Knightly C, Handler SD; et al. (2000). "Communication disorders in the 22Q11.2 microdeletion syndrome". J Commun Disord. 33 (3): 187–203, quiz 203-4. doi:10.1016/S0021-9924(00)00018-6. PMID 10907715.
- ↑ Persson C, Niklasson L, Oskarsdóttir S, Johansson S, Jönsson R, Söderpalm E (2006). "Language skills in 5-8-year-old children with 22q11 deletion syndrome". Int J Lang Commun Disord. 41 (3): 313–33. doi:10.1080/13682820500361497. PMID 16702096.