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2007-2

The Differential Diagnosis of Congenital Disorders that Include Psychosis

Margo D. Lauterbach University of Massachusetts Medical School

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Repository Citation Lauterbach MD, Stanislawski-Zygaj A, Benjamin S. (2007). The Differential Diagnosis of Congenital Disorders that Include Psychosis. Psychiatry Publications and Presentations. Retrieved from https://escholarship.umassmed.edu/psych_pp/477

This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Psychiatry Publications and Presentations by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. THE DIFFERENTIAL DIAGNOSIS OF CONGENITAL DISORDERS THAT INCLUDE PSYCHOSIS Margo Lauterbach, MD Aimee Stanislawski-Zygaj, MDa Sheldon Benjamin, MD Department of Psychiatry, UMass Medical School, UMass Memorial Healthcare Worcester, MA aCurrently: VA Western New York; Department of Psychiatry, SUNY Buffalo School of Medicine and Biomedical Sciences

BACKGROUND: Neuropsychiatrists are often called upon to evaluate TABLE THREE: DIAGNOSES WITH LESS OBVIOUS PHENOTYPES RESULTS: We identified 61 congenital disorders that psychotic individuals for possible neurological or neurodevelopmental may present from childhood through middle age and etiologies after acquired neurological and other medical disorders LEGEND CODE DIAGNOSIS WORKUP include psychosis. have been ruled out. A large number of relatively rare congenital Autism N/A neuropsychiatric conditions that include psychosis have been described. PREVALENCE D S Z Cerebrotendinous Xanthomatosis B: · cholestanol Clear guidance on the neuropsychiatric evaluation and differential Kartagener Syndrome T: mucosal biopsy • 44 disorders (72%) have prominent associated neurological features that facilitate differential diagnosis of these conditions is difficult to find in standard textbooks. >1/10,000 Z Tuberous Sclerosis X: MRI & CT calcified nodules diagnosis. OBJECTIVE: To address this dearth of information we set out to M Homocysteinuria B/U: · methionine & homocysteine

MR • 17 disorders have readily recognizable unique concisely describe the neurodevelopmental disorders in the differential 1/10,000-1/50,000 M MR with Psychosis, Pyramidal Signs, G: mutation analysis diagnosis of psychosis, their neurodiagnostic and laboratory evaluations, and Macroorchidism (PPX-M) phenotypes. and relative prevalence. <1/50,000 Z Neurocutaneous Melanosis X: MRI melanin deposits • 44 disorders may present without mental METHODS: A literature search was conducted for disorders that M Z Succinic Semialdehyde U: · γ-hydroxybutyric acid retardation. Dehydrogenase (SSADH) Deficiency may present with psychosis, utilizing PubMed and Ovid, with search Disorder’s color indicates 52 disorders (85%) have characteristic laboratory its prevalence. • terms including psychosis, metabolic, genetic, congenital and features. neurodevelopmental disorders. All disorders described in case reports N Acute Intermittent Porphyria U: · porphobilinogen & δ−aminolevulinic acid 52 have known genetic loci and 3 disorders have or case series and literature reviews, including their references, were Asperger’s NA • loci yet unkown. initially included. Epidemiological and diagnostic information was Gilbert Syndrome B: fluctuating · indirect bilirubin 1 2 3 NEURO CODES gathered via textbooks, OMIM , GENETests , and orphanet . Glucose-6-Phosphate B: RBC G6PD test • 5 disorders were due to chromosomal D = Dementia Dehydrogenase Deficiency nondisjunction. Exclusion Criteria: 1. Acquired (non-heritable/non-congenital) M = Movement disorder D M Huntington Disease G: CAG repeats disorders N = Neuropathy 2. Fewer than 3 cases reported with psychosis S = Spasticity Neurofibromatosis, Type 1 NA 3. Poorly described psychosis Z = Seizures Velo-Cardio-Facial Syndrome G: FISH Analysis: Disorders were categorized as follows: XXX Karyotype G: XXX DISCUSSION: 1. By the presence of one or more of 20 associated signs (Table One) D N Z Adrenoleukodystrophy B: · VLCFA 1. Case-report based research such as this is limited by difficulty in determining whether a reported re- Disorders having major associated neurological signs are presented N Fabry Disease B: ‚ α-galactosidase A WORKUP CODES lationship is coincidental or causal. in Tables Two and Three along with principal diagnostic tests B = Bloodwork D M N S Metachromatic Leukodystrophy B: ‚ arylsulfatase A G = Genetic test/ karyotype 2. The cost of doing an exhaustive laboratory eval- TABLE ONE: ASSOCIATED SIGNS N Porphyria Variegata U: · porphobilinogen & δ−aminolevulinic acid NEURO SIGNS (Tables 2 & 3) Dermatologic Hepatic/Splenic Abnormality O = Other uation of all possible disorders that could result D M Wilson Disease B: ‚ ceruloplasmin & · copper Mental Retardation Dysmorphic features Endocrine Abnormality S = Stool in psychosis would be astronomical. A coherent Dementia Abnormal Body Size Genitourinary Abnormality T = Tissue biopsy XYY Karyotype G: XYY neuropsychiatric approach, such as the one pre- Movement Disorder Visual Signs Skeletal/Connective Tissue Abnormality U = Urine Albright Hereditary Osteodystrophy B: ‚calcium; · phosphorus & PTH; Neuropathy Hearing Loss Hematologic Disorder X = Radiology sented here, increases cost savings by providing Spasticity Speech Abnormality Vascular Pathology NON-MR Ellsworth-Howard test a probability-guided, examination-based approach N Chester Porphyria Seizures Cardiac Abnormality None U: · porphobilinogen & δ−aminolevulinic acid to focus the workup. Darier Disease T: skin biopsy 2. By unique phenotypic features (“Doorway Diagnoses”—Table Two) 3. Accurate neuropsychiatric diagnosis guides D M Z Dentatorubral-Pallidolysian Atrophy G: CAG repeats genetic counseling and treatment planning. 3. By prevalence (> 1/10,000; 1/10,000-1/50,000; <1/50,000) (DRPLA) D M Z Fahr Disease X: BG calcification 4. Studying neuropsychiatric disorders of known eti- ‡ TABLE TWO: “DOORWAY DIAGNOSES” Familial Hemiplegic Migraine G: CACNA1A gene mutation ology that include psychosis will ultimately lead to research aimed at understanding the etiology of CODE DIAGNOSIS FEATURE WORKUP Gaucher Disease, Type 1 B: ‚ β-glucosidase D Down Syndrome dysmorphic, short G: trisomy 21 psychotic symptoms in Axis I disorders. M Z Gaucher Disease, Type 3 B: ‚ -glucosidase Fragile X Syndrome dysmorphic G: CGG repeats β D Gerstmann-Sträussler-Scheinker G: PRNP mutation SZ Phenylketonuria blond, blue-eyed, dry skin, musty odor B: · phenylalanine N Hereditary Coproporphyria Coffin-Lowry Syndrome dysmorphic, short X: XR distal phalangeal tufting U/S: · coproporphyrin CONCLUSION: As consultants frequently called MR Prader Willi Syndrome dysmorphic, short, obese G: DNA methylation analysis D N S Hereditary Spastic Paraparesis G: SPG4 gene mutation upon to evaluate atypical presentations of psychosis, S Laurence-Moon/Biedl-Bardet dysmorphic, short, obese NA D M Z Kuf Disease T: brain, muscle, or skin biopsy neuropsychiatrists should be aware of congenital Lujan-Fryns Syndrome dysmorphic, marfanoid NA D M Late Onset Tay-Sachs B: ‚ hexosaminidase A activity disorders that can present with psychosis, however Norrie Disease hearing and vision impairment G: mutation analysis rarely. We recommend a differential diagnostic D M Z Mitochondrial Encephalopathy, B: · lactate, ‚ pyruvate Wolfram Syndrome hearing and vision impairment NA Lactic Acidosis, and Stroke-Like approach based on estimated prevalence of the Episodes (MELAS) disorders and their most prominent associated Klinefelter Syndrome XXY tall, long arms G: XXY M Myoclonus-Dystonia G: SGCE gene mutation neuropsychiatric features. Marfan Syndrome dysmorphic, marfanoid NA D M Z Nasu-Hakola X: polycystic osseous lesions Oculocutaneous Albinism hypopigmented skin and hair, blue to G: mutation analysis D M Z Neimann-Pick Disease Type C T: skin biopsy (fibroblasts) yellow-brown irides REFERENCES: Turner Syndrome dysmorphic, short, obese, webbed neck G: XO D M N Z Neuroacanthocytosis B: acanthocytosis; X: MRI caudate nuclei atrophy 1. OMIM (Online Mendelian Inheritance in Man): http:// Z Sturge-Weber Syndrome port-wine stain X: MRI/CT angiomatosis/gyral D M Neurodegeneration with Brain Iron X: MRI T2 central pallidal hyperintensity with www.ncbi.nlm.nih.gov/entrez/query fcgi?db=OMIM calcifications (railroad track sign) Accumulation (NBIA) hypointense surround (‘eye of the tiger’ sign) NON-MR M Tourette Syndrome motor & vocal tics NA D M N Olivopontocerebellar Atrophy X: MRI & CT olivopontocerebellar atrophy 2. GENETests: http://www.genetests.org Usher Syndrome hearing and vision impairment O: ERG & ENG D M S Pelizeus-Merzbacher Disease X: MRI white matter disease 3. Orphanet: http://www.orpha.net Werner Syndrome short, stocky, premature aging, beaked NA M S Spinocerebellar Degenerations G: CAG repeats nose ‡ “Doorway Diagnoses” can be recognized by their unique phenotypic features