Table 2 Red flags for a possible genetic diagnosis in child psychiatry patients
From: Overview: referrals for genetic evaluation from child psychiatrists
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 |