- Commentary
- Open Access
Overview: referrals for genetic evaluation from child psychiatrists
https://doi.org/10.1186/s13034-016-0095-6
© Press et al. 2016
- Received: 5 August 2015
- Accepted: 22 February 2016
- Published: 28 March 2016
Abstract
A growing multitude of known genetic diagnoses can result in presentation to child psychiatry. For numerous reasons, it is important to identify a genetic etiology in child psychiatry patients when it is present. Genetic diagnoses can guide treatment and enable access to specialized clinics and appropriate screening measures. They can also allow for genetic counseling for the patient and family. A better understanding of etiology with a named diagnosis can itself be of great value to many patients and families; prognostic information can be empowering. Since patients with genetic conditions may present to psychiatric care in diverse ways, child psychiatrists must decide who to refer for genetic evaluation. Here we create a table to provide a framework of concerning/notable history and exam features that a practicing child psychiatrist may encounter that should prompt one to consider whether a larger, unifying genetic diagnosis is at hand. We hope this framework will facilitate referral of child psychiatry patients to genetics so that more patients can benefit from an appropriate diagnosis.
Keywords
- Diagnosis
- Genetics
- Child psychiatry
Background
A growing multitude of known genetic diagnoses can result in presentation to child psychiatry. The prevalence of genetic diagnoses among child psychiatry patients is best studied for autism, where 10–20 % of cases have a diagnosable genetic cause [e.g. Fragile X (FXS)] [1–6]. There is little information about the prevalence of genetic conditions in child psychiatry patients more generally. There are a large number of different genetic conditions that may lead to psychiatric presentation in a child. A December 2015 search of the Online Mendelian Inheritance in Man database (OMIM.org®), a catalog of genetic conditions, reveals 42 genetic etiologic associations for both psychiatric symptoms and autism. As genetic understanding continues to progress, the overlap with child psychiatry grows and it becomes increasingly important for child psychiatrists to recognize signs of a possible underlying genetic diagnoses [7].
In some instances, a genetic condition may have a typical psychiatric presentation and psychiatric symptoms may appear isolated. In such cases, presentation may be indistinguishable from that of a typical psychiatric patient whose disease is polygenic and multifactorial and genetic diagnosis is more difficult [8]. However, in many cases a genetic etiology may be suggested by features of history or physical exam. If child psychiatrists are aware of red flags signifying possible genetic condition, more patients can be appropriately diagnosed.
This article addresses two questions: Why is it important to diagnose genetic conditions in child psychiatry patients? What should prompt a child psychiatrist to request a genetic consult for a patient?
Main text
Benefits of diagnosing genetic conditions
Identifying a genetic etiology in child psychiatry patients has many benefits [9]. Diagnosis of specific genetic conditions can guide treatment and allow access to specialized healthcare. For example, depression may herald Wilson disease, which can be effectively treated with chelators [10]. In metabolic disorders with psychiatric symptoms, a diagnosis can allow for appropriate management to avoid metabolic decompensations, which worsen both psychiatric and somatic symptoms [8]. In children with FXS, hyperactivity responds particularly well to methylphenidate. Hyperactivity is more responsive to methylphenidate as part of FXS versus part of autism spectrum disorder or intellectual disability, or possibly even non-specific ADHD [3]. When diagnosed, these patients can be put directly on methylphenidate and avoid many medication trials, which carry associated risks. Furthermore, because psychiatric symptoms may arise years before more specific organic signs, certain treatments may be more effective at the ‘psychiatric stage’ before occurrence of irreversible lesions. This is particularly true for metabolic disorders [11]. Genetic diagnosis also enables access to specialized clinics with greater understanding of and experience with these complex presentations [12]. There are a growing number of condition-specific and neurogenetic clinics that may be very beneficial to patients. Because wait times to appointments can be challenging, other consultation strategies (e.g. telehealth) may be considered.
Additionally, some genetic conditions are associated with known medical complications and may require routine screening or further medical work-up. For example, a patient presenting with autism spectrum disorder and macrocephaly who is found to have a PTEN mutation can then be enrolled in a cancer screening protocol. Further, diagnosis can allow for appropriate genetic counseling for the patient and family [12, 13].
Finally, a better understanding of etiology with a named diagnosis may itself be of great value to many. Most individuals would rather know they have a serious disease than continue without a diagnosis [14]. Diagnosis allows for improved understanding, educational planning, and social support, and peer networking [15, 16]. Prognostic information can be empowering.
Indications for genetic consultation
It is not practical to conduct a genetic workup on all patients, so child psychiatrists must decide whom to refer for genetic evaluation [1]. Child psychiatrists are in an important position to diagnose genetic conditions, as they often see children for whom a diagnosis has been elusive, who have unusual presentations, or who have been difficult to treat.
Genetic syndromes may in rare cases manifest in more general child psychiatry presentations
Psychiatric presentation | Example of genetic syndrome that may result in this presentation |
|---|---|
Anxiety | 22q11 deletion [17], Fragile X syndrome [18], Williams syndrome [19] |
Acute psychosis | Adrenoleukodystrophy [20], Porphyria [21], Niemann-Pick [21], 22q11 deletion [17] |
Conduct disorder/poor judgment/anger | Monoamine oxidase A deficiency [22] |
Hyperactivity | |
Depression | Wilson disease [24] |
Some unusual psychiatric presentations or behaviors may suggest a particular genetic etiology. Skin picking may occur in Prader-Willi syndrome [25] while severe disruptions of sleep and nail pulling suggest Smith-Magenis syndrome [26]. In many cases, non-psychiatric features of the history or exam will provide clues to genetic etiology.
Red flags for a possible genetic diagnosis in child psychiatry patients
Red flag | Explanation | Examples of genetic conditions that may include specific psychiatric components |
|---|---|---|
Medical history | ||
Autism spectrum disorder | Genetic causes can be identified in 10–20 % of autism patients [1–6] | Rett syndrome PTEN mutations Tuberous sclerosis Chromosomal copy number variants |
Intellectual disability or global developmental delay | While these findings may be purely developmental, they should be investigated further when the findings seem out of proportion to the level of developmental delay | Rett syndrome fragile X |
Psychiatric symptoms worsening with conditions leading to increased protein catabolism, such as fever, surgery, or prolonged fasting | May indicate metabolic dysfunction | |
Unusually severe presentation or prolonged recovery after minor illness | Acute intermittent porphyria | |
Cyclic or recurrent vomiting, particularly with protein intake | Organic acidemias Inborn error in pyruvate metabolism | |
Poor or atypical treatment response to medications or behavioral interventions | May indicate an alternate or additional diagnosis to explain nonstandard response/components | Prader-Willi syndrome |
Severely disrupted sleep | Smith-Magenis syndrome | |
Self-injurious behavior or skin picking | Lesch-Nyhan syndrome, Prader-Willi syndrome | |
Family history | ||
Significant family history of psychiatric conditions | Though purely psychiatric conditions may also follow a familial pattern, this could indicate an underlying genetic diagnosis | 22q11 deletion syndrome |
Significant family history of neurologic regression or progressive neurologic disorders | May represent certain autosomal dominant traits for which first symptoms are sometimes psychiatric | Huntington disease Spinocerebellar ataxias |
Family history of relatives with intellectual disabilities or many with learning disabilities | Intellectual disability and learning disabilities are part of many genetic syndromes that also have psychiatric features | Fragile X syndrome |
Born to a parent with a known cytogenetic abnormality (e.g. balanced translocation) or recurrent pregnancy loss | Translocations may become unbalanced in subsequent generations causing a variety of presentations including psychiatric disease and pregnancy loss | Unbalanced chromosomal complement |
Physical exam | ||
Dysmorphic features that are not familial | May be caused by genetic syndrome | 22q11 deletion syndrome Fragile X Submicroscopic chromosomal deletions and duplications Lysosomal storage diseases |
Single major or multiple minor and/or major physical anomalies | Branchio-oto-renal syndrome Holt Oram syndrome Chromosomal deletions or deletions | |
Striking inability to learn after many well-controlled trials | May suggest cortical dysfunction | Fragile X |
Hepatosplenomegaly | These findings would not be explained by a psychiatric diagnosis alone. In conjunction with psychiatric symptoms, these findings may suggest a unifying genetic diagnosis. | Gaucher disease Niemann-Pick disease Mucopolysaccharidoses |
Unusual body odor | Glutaric aciduria type II Phenylketonuria Isovaleric academia Maple syrup urine disease | |
Unusual dermatologic findings: multiple types of lesions, six or more café au lait macules >1.5 cm in diameter, multiple lipomas, albinism | Neurofibromatosis type I Cowden syndrome Hermansky-Pudlak syndrome | |
Unexplained neurologic findings Intractable seizures Hypertonia or hypotonia Peripheral neuropathy Myopathy Progressive ataxia | Gaucher disease Neuronal ceroid lipofuscinosis Mitochondrial disorders Inborn errors of metabolism including leukodystrophies Prader-Willi syndrome Angelman syndrome Charcot-Marie-Tooth disease Spinocerebellar ataxias | |
Evidence of a connective tissue disorder Joint laxity Poor wound healing Marfanoid habitus | Homocystinuria Ehlers Danlos syndrome | |
Unexplained lab anomalies Acidosis Persistent hypoglycemia Adrenal insufficiency | Organic acidemias Beckwith-Wiedemann syndrome Adrenoleukodystrophy | |
Abnormal brain MRI findings | Tuberous sclerosis Leukodystrophies Spinocerebellar ataxias, Alexander disease | |
Microcephaly | Fetal alcohol syndrome, Williams syndrome | |
Failure to thrive or short stature | While psychiatric illness may lead to growth abnormalities, these abnormalities should be evaluated further when they cannot be fully explained by psychiatric disease | Various chromosomal conditions |
If one or more of these red flags are present, a child psychiatrist should consider requesting a genetic consultation. Whenever possible, genetic tests should be ordered in conjunction with a genetic team. On a practical level, determining which genetic tests to order can be confusing and outside the usual practice of most child psychiatrists. Even more important, many child psychiatrists are not comfortable explaining the intricacies of genetic testing and lack the infrastructure to deal with ramifications of positive results [28]. Informed consent must include discussion of the risks of genetic testing, which include harms associated with resultant treatments and incidental findings that can be life changing or psychologically disruptive [29]. There may be particular cases in which a child psychiatrist has experience with or training relevant to a certain genetic test and feels comfortable ordering this test, so this remains an individual call. However, in most cases it is best to involve a genetic team and employ their associated infrastructure. It is our hope that this table will help child psychiatrists communicate with genetic teams by allowing them to pinpoint the red flags that led them to consider a genetic etiology.
Conclusions
Short list of tips and resources for making genetic diagnoses in child psychiatry
1. | Take a family history |
2. | Measure and plot head circumference percentiles |
3. | Inspect the skin |
4. | Take note of dysmorphic features |
5. | Know your genetics referral colleagues |
6. | Short list of genetic resources GeneReviews®: http://www.genereviews.org/ Online Mendelian Inheritance in Man (OMIM)®: http://www.omim.org/ Genetics Home Reference: http://ghr.nlm.nih.gov/ |
Declarations
Authors’ contributions
All authors have substantially contributed to the manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Authors’ Affiliations
References
- Schiff M, Benoist JF, Aissaoui S, Boespflug-Tanguy O, Mouren MC, de Baulny HO, Delorme R. Should metabolic diseases be systematically screened in nonsyndromic autism spectrum disorders? PLoS One. 2011;6(7):e21932.View ArticlePubMedPubMed CentralGoogle Scholar
- Buxbaum JD, Cai G, Chaste P, Nygren G, Goldsmith J, Reichert J, Anckarsater H, Rastam M, Smith CJ, Silverman JM, Hollander E, Leboyer M, Gillberg C, Verloes A, Betancur C. Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(4):484–91.View ArticlePubMedPubMed CentralGoogle Scholar
- Roberts JE, Miranda M, Boccia M, Janes H, Tonnsen BL, Hatton DD. Treatment effects of stimulant medication in young boys with fragile X syndrome. J Neurodev Disord. 2011;3(3):175–84.View ArticlePubMedPubMed CentralGoogle Scholar
- Cochran DM, Dvir Y, Frazier JA. “Autism-plus” spectrum disorders: intersection with psychosis and the schizophrenia spectrum. Child Adolesc Psychiatr Clin N Am. 2013;22(4):609–27.View ArticlePubMedGoogle Scholar
- Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2014;86(5):749–64.View ArticleGoogle Scholar
- Shen J, Lincoln S, Miller DT. Advances in genetic discovery and implications for counseling of patients and families with autism spectrum disorders. Curr Genet Med Rep. 2014;2(3):124–34.View ArticleGoogle Scholar
- Hyman SE. The genetics of mental illness: implications for practice. Bull World Health Organ. 2000;78(4):455–63.PubMedPubMed CentralGoogle Scholar
- Sedel F, Baumann N, Turpin JC, Lyon-Caen O, Saudubray JM, Cohen D. Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults. J Inherit Metab Dis. 2007;30(5):631–41.View ArticlePubMedGoogle Scholar
- ACMG Board of Directors. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2015;17(6):505–7.View ArticleGoogle Scholar
- Zimbrean PC, Schilsky ML. The spectrum of psychiatric symptoms in Wilson’s disease: treatment and prognostic considerations. Am J Psychiatry. 2015;172(11):1068–72.View ArticlePubMedGoogle Scholar
- Demily C, Sedel F. Psychiatric manifestations of treatable hereditary metabolic disorders in adults. Ann Gen Psychiatry. 2014;13:27.View ArticlePubMedPubMed CentralGoogle Scholar
- Schaefer GB, Mendelsohn NJ, Professional Practice and Guidelines Committee: Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15(5):399–407.View ArticlePubMedGoogle Scholar
- Butler MG, Dasouki MJ, Zhou XP, Talebizadeh Z, Brown M, Takahashi TN, Miles JH, Wang CH, Stratton R, Pilarski R, Eng C. Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet. 2005;42(4):318–21.View ArticlePubMedPubMed CentralGoogle Scholar
- Gahl WA, Tifft CJ. The NIH undiagnosed diseases program: lessons learned. JAMA. 2011;305(18):1904–5.View ArticlePubMedGoogle Scholar
- Saul R. Medical genetics in pediatric practice. 1st ed. American Academy of Pediatrics; 2013.Google Scholar
- Reiff M, Giarelli E, Bernhardt BA, Easley E, Spinner NB, Sankar PL, Mulchandani S. Parents’ perceptions of the usefulness of chromosomal microarray analysis for children with autism spectrum disorders. J Autism Dev Disord. 2015;45(10):3262–75.View ArticlePubMedGoogle Scholar
- Stephenson DD, Beaton EA, Weems CF, Angkustsiri K, Simon TJ. Identifying patterns of anxiety and depression in children with chromosome 22q11.2 deletion syndrome: comorbidity predicts behavioral difficulties and impaired functional communications. Behav Brain Res. 2015;276:190–8.View ArticlePubMedPubMed CentralGoogle Scholar
- Saldarriaga W, Tassone F, Gonzalez-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R. Fragile X syndrome. Colomb Med (Cali). 2014;45(4):190–8.Google Scholar
- Ng R, Fillet P, DeWitt M, Heyman GD, Bellugi U. Reasoning about trust among individuals with Williams syndrome. Am J Intellect Dev Disabil. 2015;120(6):527–41.View ArticlePubMedGoogle Scholar
- Ramos-Rios R, Berdullas J, Arauxo A, Santos-Garcia D. Schizophreniform psychosis at onset of adrenoleukodystrophy. CNS Spectr. 2009;14(12):711–2.PubMedGoogle Scholar
- Bonnot O, Herrera PM, Tordjman S, Walterfang M. Secondary psychosis induced by metabolic disorders. Front Neurosci. 2015;9:177.View ArticlePubMedPubMed CentralGoogle Scholar
- Bortolato M, Shih JC. Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. Int Rev Neurobiol. 2011;100:13–42.View ArticlePubMedPubMed CentralGoogle Scholar
- Russell HF, Wallis D, Mazzocco MM, Moshang T, Zackai E, Zinn AR, Ross JL, Muenke M. Increased prevalence of ADHD in Turner syndrome with no evidence of imprinting effects. J Pediatr Psychol. 2006;31(9):945–55.View ArticlePubMedGoogle Scholar
- Alam ST, Rahman MM, Islam KA, Ferdouse Z. Neurologic manifestations, diagnosis and management of Wilson’s disease in children—an update. Mymensingh Med J. 2014;23(1):195–203.PubMedGoogle Scholar
- Rice LJ, Einfeld SL. Cognitive and behavioural aspects of Prader-Willi syndrome. Curr Opin Psychiatry. 2015;28(2):102–6.PubMedGoogle Scholar
- Finucane B, Dirrigl KH, Simon EW. Characterization of self-injurious behaviors in children and adults with Smith-Magenis syndrome. Am J Ment Retard. 2001;106(1):52–8.View ArticlePubMedGoogle Scholar
- Pletcher BA, Toriello HV, Noblin SJ, Seaver LH, Driscoll DA, Bennett RL, Gross SJ. Indications for genetic referral: a guide for healthcare providers. Genet Med. 2007;9(6):385–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Cohen J, Hoon A, Wilms Floet AM. Providing family guidance in rapidly shifting sand: informed consent for genetic testing. Dev Med Child Neurol. 2013;55(8):766–8.PubMedGoogle Scholar
- Ross LF, Saal HM, David KL, Anderson RR, American Academy of Pediatrics, American College of Medical Genetics and Genomic: Technical report: Ethical and policy issues in genetic testing and screening of children. Genet Med. 2013;15(3):234–45.View ArticlePubMedGoogle Scholar
