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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 [16] 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
 Unusual body odor Glutaric aciduria type II
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
  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
Ehlers Danlos syndrome
 Unexplained lab anomalies
  Persistent hypoglycemia
  Adrenal insufficiency
Organic acidemias
Beckwith-Wiedemann syndrome
 Abnormal brain MRI findings Tuberous sclerosis
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