[Diagnostic investigations for an unexplained developmental disability].

Area of Science:

• Genetics and Genomics
• Developmental Neuroscience
• Pediatric Medicine

Context:

• Developmental disability is a significant public health concern with diverse etiologies.
• Previous diagnostic strategies for mental retardation are evolving with new molecular technologies.
• Reference centers for rare diseases have updated investigation protocols for nonsyndromal mental disability.

Purpose:

• To provide an updated, evidence-based protocol for investigating nonsyndromal mental disability.
• To integrate recent advancements in genetics, genomics, and metabolic diagnostics.
• To guide clinicians in selecting appropriate diagnostic tests based on availability and clinical presentation.

Summary:

• Recommends array comparative genomic hybridization (CGH) as a primary diagnostic tool when available.
• Suggests a combination of karyotype, MLPA, fragile X screening, and targeted metabolic tests (CDG, thyroid hormone carrier deficiency, creatine metabolism deficiency) if array CGH is not feasible.
• Recommends MRI only in specific clinical scenarios such as abnormal head size, neurological findings, regression, or severe developmental delay.

Impact:

• Facilitates earlier and more accurate diagnosis of the underlying causes of developmental disabilities.
• Improves patient management and genetic counseling by identifying specific genetic and metabolic etiologies.
• Contributes to a more efficient and cost-effective diagnostic pathway for rare developmental disorders.