Commentary
Open Access

Overview: referrals for genetic evaluation from child psychiatrists

  • Katharine R. Press1Email author,
  • Laura Wieczorek2,
  • Julie Hoover-Fong3,
  • Joann Bodurtha3 and
  • Lynn Taylor4
Child and Adolescent Psychiatry and Mental Health201610:7

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.

Patients with genetic conditions may present to psychiatric care in diverse ways. Table 1 shows genetic conditions that may in rare cases account for typical child psychiatry presentations. Psychiatric symptoms may be apparently isolated, making genetic diagnosis difficult. However, often a careful history and physical provides hints to a genetic diagnosis.
Table 1

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

Turner syndrome [23], Fragile X syndrome [3]

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.

The purpose of Table 2 is to present a framework of notable history and exam features that should prompt a child psychiatrist to consider whether there is a larger, unifying genetic diagnosis at hand. All of these features are recognized as markers in pediatric genetic practice, however here the goal is to isolate the flags most likely to present in a child psychiatry practice [27]. This table is just a starting point and should not be considered exhaustive.
Table 2

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

It is important to identify a genetic etiology in child psychiatry patients when it is present, as it has implications for treatment and counseling. Patients with genetic conditions may have unusual psychiatric symptoms or other abnormal history and physical findings. Here we present a table of red flags that a practicing child psychiatrist may identify, which could indicate an underlying genetic diagnosis. We hope this table will inspire child psychiatrists to think about genetic possibilities in their patient populations and make referrals for genetic evaluation when appropriate. Future work will be needed to validate this table in practice. However, being aware of these the flags has immediate utility in the clinical practice of child psychiatrists. To highlight how simple practice changes may have a big impact for diagnosing conditions, we provide a short list of tips and resources for making a genetic diagnosis in child psychiatry (Table 3). We hope that this commentary will encourage child psychiatrists to think about their growing overlap with the field of genetics. Recognition of the importance of genetic diagnoses in child psychiatry patients may stimulate more research into the prevalence of genetic disease, effective methods of screening and diagnosis, and strategies for treatment and management for these patients.
Table 3

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

(1)
(2)
Bloomberg Children’s Center
(3)
Blalock 1008 Medical Genetics
(4)
Bloomberg Children’s Center

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Copyright

© Press et al. 2016

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