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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 1 core gene, 12 core candidate genes and altogether 62 curated genes according to the clinical signs

ID
MP9485
Number of genes
34 Accredited laboratory test
Examined sequence length
19,0 kb (Core-/Core-canditate-Genes)
116,5 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-GReferenz-Seq.Heredity
CDKN1C951NM_000076.2AD
EZH22256NM_004456.5AD
FMR11899NM_002024.6XL
NFIA1497NM_005595.5AD
NFIB1485NM_001190737.2AD
NFIX1533NM_001271043.2AD
NSD18091NM_022455.5AD
PTEN1212NM_000314.8AD
ADK1038NM_001123.4AR
APC26912NM_005883.3AR
BRWD35409NM_153252.5XLR
CACNA1E6813NM_000721.4AD
CHD36180NM_001005271.3AD
CUL4B2742NM_003588.4XLR
DICER15769NM_177438.3SMu
EED2100NM_003797.5AD
EXT22157NM_207122.2AR
GCDH1317NM_000159.4AR
GRIA32685NM_000828.5XLR
H1-4661NM_005321.3AD
HERC114586NM_003922.4AR
HRAS570NM_005343.4AD
HUWE113125NM_031407.7XLR
KPTN1311NM_007059.4AR
MED126534NM_005120.3XL
NONO1426NM_001145408.2XL
PAK11702NM_001128620.2AD
PPP2R5D1356NM_006245.4AD
RAB39B642NM_171998.4XLR
RHEB583NM_005614.4AD
SHANK35386NM_001372044.2AD
SNX142841NM_153816.6AR
SUZ122220NM_015355.4AD
UPF3B1452NM_080632.3XLR

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: Basal cell nevus syndrome 1 (PTCH1)
  • Allelic: Basal cell nevus syndrome 2 (SUFU)
  • Allelic: Congenital myopathy with excess of muscle spindles (HRAS)
  • Allelic: Cortical dysplasia, complex, with other brain malformations 10
  • Allelic: Fragile X tremor/ataxia syndrome (FMR1)
  • Allelic: Glioma susceptibility 2 (PTEN)
  • Allelic: Goiter, multinodular 1,+/- Sertoli-Leydig cell tumors (DICER1)
  • Allelic: Intellectual developmental disorder, AD 44, with microcephaly (TRIO)
  • Allelic: Lujan-Fryns syndrome (MED12)
  • Allelic: Lymphangioleiomyomatosis (TSC1)
  • Allelic: Medulloblastoma (SUFU)
  • Allelic: Meningioma (PTEN)
  • Allelic: Meningioma, familial, susceptibility to (SUFU)
  • Allelic: Ohdo syndrome, XL (MED12)
  • Allelic: Pleuropulmonary blastoma (DICER1)
  • Allelic: Premature ovarian failure 1 (FMR1)
  • Allelic: Prostate cancer, somatic (PTEN)
  • Allelic: Rhabdomyosarcoma, embryonal, 2 (DICER1)
  • Allelic: Waisman syndrome (RAB39B)
  • Bachmann-Bupp syndrome (ODC1)
  • Beck-Fahrner syndrome (TET3)
  • Beckwith-Wiedemann syndrome (CDKN1C)
  • Brain malformations with/-out urinary tract defects (NFIA)
  • Cohen-Gibson syndrome (EED)
  • Costello syndrome (HRAS)
  • Cowden syndrome 1 (PTEN)
  • Cowden syndrome 5 (PIK3CA)
  • Epileptic encephalopathy, early infantile, 69 (CACNA1E)
  • Familial Wilms tumor [GeneReviews] (CTR9)
  • Fragile X syndrome (FMR1)
  • GAND syndrome (GATAD2B)
  • GLOW syndrome, somatic mosaic: Global dev. delay, Lung cysts, Overgrowth, Wilms tumor (DICER1)
  • Global develop delay, intellectual disability, macrocephal, alopecia, ectodermal dysplasia (ODC1)
  • Glutaricaciduria, type I (GCDH)
  • Holoprosencephaly 7 (PTCH1)
  • Hypermethioninemia due to adenosine kinase deficiency (ADK)
  • ID [MONDO:0001071], macrocephaly [HP:0000256] (CTR9)
  • IMAGE syndrome (CDKN1C)
  • Imagawa-Matsumoto syndrome (SUZ12)
  • Intellectual developmental disorder with autism + macrocephaly (CHD8)
  • 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, AD 70 (SETD2)
  • Intellectual developmental disorder, XL, syndromic, Wu type (GRIA3)
  • Intellectual disability, macrocephaly [panelapp] (ATXN2L)
  • Joubert syndrome 32 (SUFU)
  • Kleefstra syndrome 1 (EHMT1)
  • Lhermitte-Duclos syndrome (PTEN)
  • Luscan-Lumish syndrome (SETD2)
  • 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)
  • Neurodevelopmental disorder, language delay +/- structural brain abnormalities (PPP2CA)
  • Opitz-Kaveggia syndrome (MED12)
  • Phelan-McDermid syndrome (SHANK3)
  • Polyhydramnios, megalencephaly + symptomatic epilepsy (STRADA syn. LYK5)
  • Polyhydramnios, megalencephaly + symptomatic epilepsy (STRADA)
  • Rabin-Pappas syndrome (SETD2)
  • Rahman syndrome (HIST1H1E)
  • Short stature, macrocephaly, intellectual disability + autism spectrum disorder [panelapp] (RHEB)
  • Simpson-Golabi-Behmel syndrome, type 1 (GPC3)
  • Smith-Kingsmore syndrome (MTOR)
  • Snijders Blok-Campeau syndrome (CHD3)
  • Sotos syndrome 1 (NSD1)
  • Sotos syndrome 2 (NFIX)
  • Sotos syndrome 3 (APC2)
  • Spinocerebellar ataxia, AR 20 (SNX14)
  • Tenorio syndrome (RNF125)
  • Thauvin-Robinet-Faivre syndrome (FIBP)
  • Tuberous sclerosis-1 (TSC1)
  • Tuberous sclerosis-2 (TSC2)
  • Weaver syndrome (EZH2)
Heredity, heredity patterns etc.
  • AD
  • AR
  • SMu
  • XL
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined