IllnessIntellectual deficit + macrocephaly, differential diagnosis

NGS +

[Sanger]

Intellectual disability is due to neurological developmental deficits and is characterised by limitations in intellectual functioning and adaptive behaviour (lack of competence in social, conceptual and practical skills). The most common chromosomal cause of intellectual disability is Down syndrome, the most common genetic cause is Fragile X syndrome, and the most common known preventable or environmental cause is fetal alcohol syndrome. Many genetic disorders include macrocephaly as well as intellectual deficits. The latter is a broad term that includes megalencephaly and other causes of enlargement of the head without cerebral overgrowth, such as subdural fluid accumulation. Macrocephaly is common (2.5% of the population) and is often (partly) genetic (<200 OMIM entries). In a number of syndromes, mental retardation and macrocephaly occur in combination: Beckwith-Wiedemann, Cowden, IMAGE, Sotos, Marshall-Smith, Weaver and rarer syndromes; holoprosencephaly, hydrocephalus, leukodystrophies, etc. An inconspicuous genetic finding does not mean that the suspected clinical diagnosis is excluded.

References: https://www.ncbi.nlm.nih.gov/books/NBK560786/

https://www.ncbi.nlm.nih.gov/books/NBK148820/

https://www.ncbi.nlm.nih.gov/books/NBK542336/

https://www.ncbi.nlm.nih.gov/books/NBK1479/

https://www.ncbi.nlm.nih.gov/books/NBK1151/

https://www.ncbi.nlm.nih.gov/books/NBK1488/

• Alias: Intellectual disability, macrocephaly
• Alias: Psycho-motor retardation, macrocephaly
• Allelic: Basal cell carcinoma, somatic (PTCH1)
• Allelic: Basal cell nevus syndrome (PTCH1)
• Allelic: Cortical dysplasia, complex, with other brain malformations 10
• Allelic: Glioma susceptibility 2 (PTEN)
• Allelic: Intellectual developmental disorder, AD 44, with microcephaly (TRIO)
• Allelic: Lujan-Fryns syndrome (MED12)
• Allelic: Meningioma (PTEN)
• Allelic: Ohdo syndrome, XL (MED12)
• Allelic: Prostate cancer, somatic (PTEN)
• Allelic: Waisman syndrome (RAB39B)
• Bachmann-Bupp syndrome (ODC1)
• Beckwith-Wiedemann syndrome (CDKN1C)
• Brain malformations with/-out urinary tract defects (NFIA)
• Cohen-Gibson syndrome (EED)
• Cowden syndrome 1 (PTEN)
• Cowden syndrome 5 (PIK3CA)
• Epileptic encephalopathy, early infantile, 69 (CACNA1E)
• GAND syndrome (GATAD2B)
• Global develop delay, intellectual disability, macrocephal, alopecia, ectodermal dysplasia (ODC1)
• Glutaricaciduria, type I (GCDH)
• Hypermethioninemia due to adenosine kinase deficiency (ADK)
• IMAGE syndrome (CDKN1C)
• Imagawa-Matsumoto syndrome (SUZ12)
• Intellectual developmental disorder with macrocephaly, seizures + speech delay (PAK1)
• Intellectual developmental disorder, AD 48 (RAC1)
• Intellectual developmental disorder, AD 63, with macrocephaly (TRIO)
• Intellectual developmental disorder, XL, syndromic, Wu type (GRIA3)
• Intellectual disability, macrocephaly [panelapp] (ATXN2L)
• Lhermitte-Duclos syndrome (PTEN)
• Macrocephaly, acquired, with impaired intellectual development (NFIB)
• Macrocephaly, dysmorphic facies, and psychomotor retardation (HERC1)
• Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, persistent fetal hemoglobin (ZBTB7A)
• Macrocephaly/autism syndrome (PTEN)
• Macrocephaly/megalencephaly syndrome, AR (TBC1D7)
• Marshall-Smith syndrome (NFIX)
• Megalencephalic leukoencephalopathy with subcortical cysts (MLC1)
• Megalencephalic leukoencephalopathy with subcortical cysts 2A (HEPACAM)
• Megalencephalic leukoencephalopathy, subcort. cysts 2B, remitting, +/- mental retardation (HEPACAM)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (PIK3R2)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (AKT3)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (CCND2)
• Mental retardation, AD 35 (PPP2R5D)
• Mental retardation, AR 41 (KPTN)
• Mental retardation, XL 72 (RAB39B)
• Mental retardation, XL 93 (BRWD3)
• Mental retardation, XL syndromic, Turner type (HUWE1)
• Mental retardation, XL, syndromic 14 (UPF3B)
• Mental retardation, XL, syndromic 15, Cabezas type (CUL4B)
• Mental retardation, XL, syndromic 34 (NONO)
• Opitz-Kaveggia syndrome (MED12)
• Phelan-McDermid syndrome (SHANK3)
• Polyhydramnios, megalencephaly + symptomatic epilepsy (STRADA)
• Rahman syndrome (HIST1H1E)
• Short stature, macrocephaly, intellectual disability + autism spectrum disorder [panelapp] (RHEB)
• Snijders Blok-Campeau syndrome (CHD3)
• Sotos syndrome 1 (NSD1)
• Sotos syndrome 2 (NFIX)
• Sotos syndrome 3 (APC2)
• Spinocerebellar ataxia, AR 20 (SNX14)
• Weaver syndrome (EZH2)