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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessIntellectual deficit + macrocephaly, differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Intellectual deficit + macrocephaly comprising 7 or altogether 45 curated genes according to the clinical signs

ID
MP9485
Number of genes
31 Accredited laboratory test
Examined sequence length
17,1 kb (Core-/Core-canditate-Genes)
108,3 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GHeredity
CDKN1C951AD
EZH22256AD
NFIA1497AD
NFIB1485AD
NFIX1533AD
NSD18091AD
PTEN1212n.k.
ADK1038AR
APC26912AR
BRWD35409XLR
CACNA1E6813AD
CHD36180AD
CUL4B2742XLR
EED2100AD
EXT22157AR
GCDH1317AR
GRIA32685XLR
H1-4661AD
HERC114586AR
HUWE113125XL
KPTN1311AR
MED126534XLR
NONO1426XL
PAK11702AR
PPP2R5D1356AD
RAB39B642XLR
RHEB583AD
SHANK35386AD
SNX142841AR
SUZ122220AD
UPF3B1452XLR

Informations about the disease

Clinical Comment

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/

 

Synonyms
  • 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)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XL
  • XLR
  • n.k.
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code
Q75.3

Bioinformatics and clinical interpretation

No text defined