IllnessIntellectual deficit, X chromosomal, non-syndromic; differential diagnosis

X NGS +

[Sanger]

The complexity of the brain and intellectual functioning mechanisms in humans is immense, as is the way in which intellectual disabilities can occur. The etiology of one third of the genetic cases with intellectual deficits is unknown. The increasing number of identified genes associated with mental retardation suggests that this phenotype may be the end result of the disruption of various interconnected cellular and molecular pathways. The most common disorder with X-linked intellectual deficit is Fragile X Syndrome (FXS), dominantly inherited with incomplete penetrance, affecting about 1-3/10 000 Caucasian men. The mutated FMR1 gene harbors excess CCG trinucleotide repeats, is hypermethylated and therefore does not produce protein. The X chromosome comprises a disproportionate number of additional genes (>140) whose mutations cause psychomotor retardation. The mechanisms of pathogenicity are usually based on point mutations and genomic rearrangements. X-linked inheritance can be both dominant and recessive, and expressiveness may vary depending on the mutated gene. An inconspicuous genetic finding does not mean that the suspected clinical diagnosis is excluded.

Reference: https://pubmed.ncbi.nlm.nih.gov/31898314/

• Alias: Intellectual disability XL
• Alias: Psycho-motor retardation XL
• Allelic: Epilepsy, XL, with variable learning disabilities + behavior disorders (SYN1)
• Allelic: FG syndrome 4 (CASK)
• Allelic: Raynaud-Claes syndrome (CLCN4)
• Asperger syndrome susceptibility, XL (NLGN3)
• Intellectual developmental disorder + microcephaly with pontine + cereb. hypoplasia (CASK)
• Intellectual developmental disorder, XL 107 (STEEP)
• Intellectual developmental disorder, XL 109 (AFF2)
• Intellectual developmental disorder, XL 50 (SYN1)
• Lissencephaly, XL (DCX)
• Mental retardation syndrome, XL, Siderius type (PHF8)
• Mental retardation, XL 1/78 (IQSEC2)
• Mental retardation, XL 104 (FRMPD4)
• Mental retardation, XL 106 (OGT)
• Mental retardation, XL 12/35 (THOC2)
• Mental retardation, XL 15 (CLCN4)
• Mental retardation, XL 21/34 (IL1RAPL1)
• Mental retardation, XL 29 and others (ARX)
• Mental retardation, XL 30/47 (PAK3)
• Mental retardation, XL 41 (GDI1)
• Mental retardation, XL 49 (CLCN4)
• Mental retardation, XL 58 (TSPAN)
• Mental retardation, XL 63 (ACSL4)
• Mental retardation, XL 72 (RAB39B)
• Mental retardation, XL 9/44 (FTSJ1)
• Mental retardation, XL 90 (DLG3)
• Mental retardation, XL 93 (BRWD3)
• Mental retardation, XL 96 (SYP)
• Mental retardation, XL 97 (ZNF711)
• Mental retardation, XL 98 (NEXMIF)
• Mental retardation, XL 99 (USP9X)
• Mental retardation, XL, syndromic 13 (MECP2)
• Mental retardation, with/-out nystagmus (CASK)
• Subcortical laminal heterotopia, XL (DCX)
• XL intellectual disability [MONDO:0100284, panelapp] (WNK3)