Language

English

Publication Date

8-1-2025

Journal

Orphanet Journal of Rare Diseases

DOI

10.1186/s13023-025-03941-8

PMID

40750893

PMCID

PMC12315305

PubMedCentral® Posted Date

8-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Rare genetic diseases (RDs) with primary neuropsychiatric symptoms pose unique challenges for diagnosis and management. While the majority of these RDs have neuropsychiatric symptoms that are secondary to the RD, a subset presents with primary neuropsychiatric symptoms directly linked to their underlying pathophysiology. This subset has significant unmet medical need with delayed diagnoses leading to prolonged delays in treatment optimization and the trialing of medications that fail to target the underlying pathophysiology. This comprehensive review identifies 108 RDs with central neuropsychiatric symptoms that have a 7.7-year average diagnostic delay. Optimal management strategies for these RDs typically includes non-psychotropic medications, dietary adjustment, avoidance of certain drug classes and other treatments that target the underlying pathophysiology before improvement of the neuropsychiatric symptoms is observed. Surprisingly, despite the limited number of RDs that fit this unique profile, the annual economic burden for these conditions had an annual mental health care-related inpatient charges totaling $4.2 billion USD. Addressing the diagnostic delay and optimizing management for these specific conditions must include increased involvement across multiple specialties, including psychiatry, family medicine, pediatrics, medical genetics, as well as an enhanced strategy for genetic testing to ensure the prompt initiation of condition-specific therapies for affected individuals.

Keywords

Humans, Cost of Illness, Delayed Diagnosis, Mental Disorders, Psychiatry, Rare Diseases

Published Open-Access

yes

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