Description
Primary Microcephaly - Microcephalic Dwarfism Spectrum inclusion criteria (36508)
•	Occipitofrontal circumference (OFC) >2 standard deviations (SD) below mean at birth AND progressive microcephaly to >4SD, OR
•	OFC >4SD below mean at birth, OR
•	OFC >3SD below mean at birth AND length >3SD below mean at birth

Primary Microcephaly - Microcephalic Dwarfism Spectrum exclusion criteria (36508)
•	A known genetic cause.
•	Dysmorphic physical features or MRI brain indicative of an alternative diagnosis
•	Evidence of an environmental cause

Prior genetic testing guidance (36508)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Primary Microcephaly - Microcephalic Dwarfism Spectrum prior genetic testing genes (36508)
Testing as below is strongly recommended PRIOR TO RECRUITMENT as diagnosis of these disorders carries important management implications:
-	Array or equivalent genome-wide copy number analysis.
-	ASPM and other genes dictated by the phenotype

Closing statement (36508)
These requirements will be kept under continual review during the main programme and may be subject to change.

The Expert list for this panel was provided by Professor Andrew Jackson, University of Edinburgh.

9 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • emma baple (South West GMC)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Richard Scott (Genomics England Curator)

    Group: Other
    Workplace: Genomics England

  • emma baple (Genomics England Curator)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Olivia Niblock (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

118 Entities

114 reviewed, 88 green

List Entity Reviews Mode of inheritance Details
118 Entitiess
Green Green List (high evidence)
5p15 terminal (Cri du chat syndrome) region Loss
ISCA-37390-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • ClinGen
Phenotypes
  • 123450
  • PMID 15635506: characteristic cry, speech delay, facial dysmorphology, and level of mental retardation. PMID 11238681: interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731, study supports hypothesis of a separate region in p15.3 for the speech delay
Green Green List (high evidence)
16p13.3 region (includes CREBBP) Loss
ISCA-37406-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • ClinGen
Phenotypes
  • PMID: 10573006 death in infancy, accessory spleens, hypoplastic left heart, abnormal pulmonary lobulation, renal agenesis (patient 1), severe neonatal seizures (patient 2). PMID 16783566: failure to thrive, life-threatening malformations, and/or critical infections, and all died in infancy (5 weeks, 7 months, and 9 months, respectivelyFrom Genetics Home Reference: short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes
  • 610543
Green Green List (high evidence)
2p15p16.1 region (includes BCL11A) Loss
ISCA-37408-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • ClinGen
Phenotypes
  • PMID: 16963482 idiopathic intellectual disability including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies (multicystic kidney, hydronephrosis), digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features. Dysmorphic craniofacial features include progressive microcephaly, flat occiput, widened inner canthal distance, small palpebral fissures, ptosis, long and straight eyelashes, broad and high nasal root extending to a widened, prominent nasal tip with elongated, smooth philtrum, rounding of the upper vermillion border and everted lower lips. PMID: 18245392 A 32-year-old, mentally retarded male was referred to our centre for further clinical genetic analysis. He was born to non-consanguineous parents after 42 weeks gestation with a birth weight of 3500 g. He had a healthy older brother. In the neonatal period he was hypotonic and at 8 weeks of age he underwent surgery because of an inguinal hernia with removal of an atrophic right testis. His motor development was severely delayed with sitting at 3.5 years and walking at 5 years of age. Speech was poorly developed, characterised by the usage of only a few words. During infancy an optic nerve hypoplasia was diagnosed, and during childhood he frequently suffered from luxations of the patellae, which required surgery. At the age of 32 years his height is 163 cm (_3 SDS) and head circumference 52.5 cm (_2.5 SDS). He has a narrow receding forehead, widened inner canthal distance of 3.5 cm (90th centile), normal outer canthal distance of 8.5 cm (25th centile), telecanthus, short and down slanting palpebral fissures, epicanthal folds, ptosis, long, straight eyelashes, high nasal bridge, low set large ears, flat philtrum, small mouth with high, narrow palate and retrognathia. The thorax is broad with increased internipple distance and slight gynaecomastia. A recent renal ultrasound revealed multiple cysts in the left, dystrophic kidney and two uncomplicated cysts in the enlarged, right kidney. The patient has a normally sized phallus with absent right testis and small left testis. His hands show a simian crease right and tapering fingers with broad proximal interphalangeal joints. He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more)
  • 612513
  • PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal cyst which has not been previously reported in other patients with this cytogenetic defect
Green Green List (high evidence)
5q35 recurrent (Sotos syndrome) region (includes NSD1) Gain
ISCA-37425-Gain
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • ClinGen
Phenotypes
  • Microcephaly, short stature and developmental delay
  • short stature, microcephaly, learning disability or mild to moderate ID, and distinctive facial features comprising periorbital fullness, short palpebral fissures, a long nose with broad or long nasal tip, a smooth philtrum and a thin upper lip vermilion. Behavioral problems, ocular and minor hand anomalies may be associated.
Green Green List (high evidence)
KIF1BP
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Goldberg-Shprintzen megacolon syndrome, 609460 (Microcephaly)
Green Green List (high evidence)
KNL1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Microcephaly 4, primary, autosomal recessive, 604321
  • Microcephaly 4, Primary, Autosomal Recessive
Green Green List (high evidence)
PRUNE1
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • microcephaly, spasticity, developmental delay
Green Green List (high evidence)
ASPM
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Other
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • Microcephaly 5, primary, autosomal recessive
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Autosomal recessive primary microcephaly (MCPH)
  • Microcephaly 5, primary, autosomal recessive, 608716
  • Microcephaly 5, Primary, Autosomal Recessive
Green Green List (high evidence)
ATR
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Seckel syndrome 1, 210600
  • MICROCEPHALIC PRIMORDIAL DWARFISM I
Green Green List (high evidence)
ATRX
2 reviews
1 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Mental retardation-hypotonic facies syndrome, X-linked, 309580 (Microcephaly)
  • Alpha-thalassemia/mental retardation syndrome, 301040 (Microcephaly)
Green Green List (high evidence)
BLM
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Bloom syndrome, 210900
  • microcephaly
Green Green List (high evidence)
BRCA2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Fanconi anemia, complementation group D1, 605724 (Microcephaly)
Green Green List (high evidence)
BRIP1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group J, 609054
Green Green List (high evidence)
CASK
1 review
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Emory Genetics Laboratory
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • CASK-related XLID
  • severe intellectual disability, brainstem and cerebellar hypoplasia, and microcephaly
  • Mental retardation and microcephaly with pontine and cerebellar hypoplasia, 300749
  • MICPCH
  • Mental Retardation And Microcephaly With Pontine And Cerebellar Hypoplasia, 300749
Green Green List (high evidence)
CDK5RAP2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Microcephaly 3, primary, autosomal recessive, 604804
  • Microcephaly 3, Primary, Autosomal Recessive
Green Green List (high evidence)
CDT1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Meier-Gorlin syndrome 4, 613804
Green Green List (high evidence)
CENPF
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Stromme syndrome, 243605
  • Microcephaly
Green Green List (high evidence)
CENPJ
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Microcephaly 6, primary, autosomal recessive, 608393
  • ?Seckel syndrome 4, 613676
  • Microcephaly
  • microcephaly primary type 6 (MCPH6), 608393
Green Green List (high evidence)
CEP135
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • UKGTN
  • Expert Review Green
  • Expert list
  • Literature
Phenotypes
  • MCPH
  • primary microcephaly
  • Autosomal recessive primary microcephaly (MCPH)
  • ?Microcephaly 8, primary, autosomal recessive, 614673
  • Primary Microcephaly and Disturbed Centrosomal Function, 614673
Green Green List (high evidence)
CEP152
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Microcephaly 9, primary, autosomal recessive, 614852
  • Seckel syndrome 5, 613823
  • microcephaly primary type 4 (MCPH4), 604321
Green Green List (high evidence)
CEP63
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • ?Seckel syndrome 6, 614728
  • Microcephaly
Green Green List (high evidence)
CIT
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Other
  • Expert Review Green
Phenotypes
  • autosomal-recessive primary microcephaly
  • MCPH
  • Microcephaly 17, primary, autosomal recessive, 617090
Green Green List (high evidence)
CKAP2L
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION
  • Filippi syndrome, 272440
Green Green List (high evidence)
CREBBP
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Rubinstein-Taybi syndrome, 180849 (microcephaly)
Green Green List (high evidence)
CTNNB1
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
  • Expert Review Green
Phenotypes
  • primary microcephaly
  • Mental retardation, autosomal dominant 19, 615075
Green Green List (high evidence)
DDX11
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Expert Review Green
Phenotypes
  • Warsaw breakage syndrome 613398
Green Green List (high evidence)
DHCR7
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Smith-Lemli-Opitz syndrome 270400
Green Green List (high evidence)
DIAPH1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • microcephaly, blindness and early onset seizures
  • severe visual impairment, intellectual disability, and short stature
  • Seizures, cortical blindness, microcephaly syndrome, 616632
Green Green List (high evidence)
DONSON
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Microcephaly, short stature, and limb abnormalities 617604
  • Microcephaly-micromelia syndrome 251230
Green Green List (high evidence)
DPP6
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • MCPH
  • primary microcephaly
  • autosomal dominant microcephaly and mental retardation
  • Mental retardation, autosomal dominant 33, 616311
Tags
  • deletions
Green Green List (high evidence)
DYRK1A
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
  • Expert Review Green
Phenotypes
  • microcephaly
  • Mental retardation, autosomal dominant 7, 614104
Tags
  • deletions
Green Green List (high evidence)
EFTUD2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Expert Review Green
Phenotypes
  • Mandibulofacial dysostosis, Guion-Almeida type 610536
Green Green List (high evidence)
ERCC4
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group Q, 61527
Green Green List (high evidence)
ERCC6
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Cockayne syndrome, type B, 133540 (Microcephaly)
Green Green List (high evidence)
ERCC8
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Cockayne syndrome, type A, 216400 (Microcephaly)
Green Green List (high evidence)
FANCA
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Fanconi anemia, complementation group A, 227650 (Microcephaly)
Green Green List (high evidence)
FANCB
1 review
1 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group B, 300514
Green Green List (high evidence)
FANCC
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group C, 227645 (Microcephaly)
Green Green List (high evidence)
FANCD2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group D2, 227646 (Microcephaly)
Green Green List (high evidence)
FANCE
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Fanconi anemia, complementation group E, 600901 (Microcephaly)
Green Green List (high evidence)
FANCF
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group F, 603467
Green Green List (high evidence)
FANCG
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group G, 614082
Green Green List (high evidence)
FANCI
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group I, 609053
Green Green List (high evidence)
FANCL
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group L, 614083
Green Green List (high evidence)
GMNN
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Other
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Meier-Gorlin syndrome 6, 616835
  • MGORS6
  • primordial dwarfism
Green Green List (high evidence)
HDAC8
1 review
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Cornelia de Lange syndrome 5, 300882 (includes Small head circumference)
Green Green List (high evidence)
IARS
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, 617093
  • Microcephaly
Green Green List (high evidence)
IER3IP1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Microcephaly, epilepsy, and diabetes syndrome, 614231
  • Microcephaly (-3 to -9 SD)
Green Green List (high evidence)
IGF1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Other
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747
  • MPD
  • microcephalic primordial dwarfism
Green Green List (high evidence)
IGF1R
1 review
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Expert Review Green
Phenotypes
  • Insulin-like growth factor I, resistance to 270450
Green Green List (high evidence)
KIF11
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Other
  • UKGTN
  • Expert Review Green
Phenotypes
  • Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation, 152950
  • Autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy, 152950
Green Green List (high evidence)
LARP7
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Alazami syndrome, 615071 (Microcephaly and short stature)
  • Primordial dwarfism
Green Green List (high evidence)
LIG4
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
  • Expert list
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • LIG4 syndrome, 606593
  • microcephaly
Green Green List (high evidence)
MCPH1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Microcephaly 1, primary, autosomal recessive, 251200
  • Microcephaly 1, Primary, Autosomal Recessive
Green Green List (high evidence)
MFSD2A
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Microcephaly 15, primary, autosomal recessive, 616486
Green Green List (high evidence)
MSMO1
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834
Green Green List (high evidence)
MYCN
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Feingold syndrome 1, 164280 (Microcephaly)
Green Green List (high evidence)
NBN
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Nijmegen breakage syndrome 251260
Green Green List (high evidence)
NDE1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Lissencephaly 4 (with microcephaly), 614019
  • ?Microhydranencephaly, 605013
Green Green List (high evidence)
NHEJ1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Expert Review Green
  • UKGTN
Phenotypes
  • Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291
Green Green List (high evidence)
NIPBL
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Cornelia de Lange syndrome 1, 122470 (includes microcephaly)
Green Green List (high evidence)
ORC1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Meier-Gorlin syndrome 1, 224690
Green Green List (high evidence)
ORC4
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • Other
  • Radboud University Medical Center, Nijmegen
  • Literature
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Meier-Gorlin syndrome 2, 613800
Green Green List (high evidence)
ORC6
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Meier-Gorlin syndrome 3, 613803
Green Green List (high evidence)
PALB2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group N, 610832 (microcephaly)
Green Green List (high evidence)
PCNT
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Microcephalic Osteodysplastic Primordial Dwarfism
  • Microcephalic osteodysplastic primordial dwarfism, type II, 210720
Green Green List (high evidence)
PDHA1
1 review
1 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Microcephaly, seizures, very variable phenotype
Green Green List (high evidence)
PLK4
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • Expert list
Phenotypes
  • MCPH
  • primary microcephaly
  • Microcephaly and chorioretinopathy, autosomal recessive, 2
  • MCCRP2
  • Microcephaly and chorioretinopathy, autosomal recessive, 2, 616171
Green Green List (high evidence)
PNKP
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • Microcephaly, seizures, and developmental delay, 613402
Green Green List (high evidence)
POC1A
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis, 614813
  • Microcephaly in adulthood
  • primordial dwarfism
  • SOFT syndrome
Green Green List (high evidence)
PQBP1
1 review
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Renpenning syndrome 309500
Green Green List (high evidence)
RAD21
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Cornelia de Lange syndrome 4, 614701 (includes microcephaly)
Green Green List (high evidence)
RBBP8
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • Other
Phenotypes
  • MCPH
  • primary microcephaly
  • Seckel syndrome 2, 606744 (‌includes microcephaly)
  • MICROCEPHALIC PRIMORDIAL DWARFISM 2
  • Jawad syndrome (microcephaly with mental retardation and digital anomalies), 251255
  • Jawad syndrome, 251255 (‌includes congenital microcephaly)
Green Green List (high evidence)
RNU4ATAC
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Radboud University Medical Center, Nijmegen
  • Expert list
  • Expert Review Green
Phenotypes
  • Microcephalic osteodysplastic primordial dwarfism, type I
  • Microcephalic osteodysplastic primordial dwarfism, type I, 210710
  • MPD
  • microcephalic primordial dwarfism
Tags
  • locus-type-rna-small-nuclear
Green Green List (high evidence)
RPL10
1 review
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Mental retardation, X-linked, syndromic, 35 300998
Green Green List (high evidence)
RTTN
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Expert Review Green
  • Expert list
  • Other
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • MCPH
  • primary microcephaly
  • Microcephaly, short stature, and polymicrogyria with seizures
  • Microcephaly,short stature,and polymicrogyria with seizures,614833
  • Microcephaly, Short Stature, And Polymicrogyria With Or Without Seizures, 614833
Green Green List (high evidence)
SLC25A19
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Amish Lethal Microcephaly
  • Microcephaly, Amish type, 607196
  • Amish Lethal Microcephaly, 216535
Green Green List (high evidence)
SLC9A6
1 review
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Emory Genetics Laboratory
  • UKGTN
  • Other
  • Expert Review Green
Phenotypes
  • Angelman-like Syndrome
  • microcephaly, seizures, ataxia, and absent speech
  • Mental retardation, X-linked syndromic, Christianson type, 300243
  • Microcephaly
Green Green List (high evidence)
SLX4
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Fanconi anemia, complementation group P, 613951 (Microcephaly)
Green Green List (high evidence)
SMC1A
1 review
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Cornelia de Lange syndrome 2, 300590 (includes microcephaly)
Tags
  • gene-duplication
Green Green List (high evidence)
SMC3
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Cornelia de Lange syndrome 3, 610759 (includes microcephaly)
Green Green List (high evidence)
STAMBP
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Microcephaly-capillary malformation syndrome 614261
Green Green List (high evidence)
STIL
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly, Recessive
  • Microcephaly 7, primary, autosomal recessive, 612703
  • Microcephaly 7, Primary, Autosomal Recessive
Green Green List (high evidence)
TOP3A
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Bloom Syndrome-like Disorder
Green Green List (high evidence)
TRAIP
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Expert Review Green
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Seckel syndrome 9, 616777
  • Microcephaly
Green Green List (high evidence)
TRMT10A
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Microcephaly, short stature, and impaired glucose metabolism 1
  • 616033
  • MSSGM1
  • primary microcephaly
Green Green List (high evidence)
TUBGCP4
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335
Green Green List (high evidence)
TUBGCP6
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Microcephaly and chorioretinopathy, autosomal recessive, 1, 251270
  • MCCRP1
  • Microcephaly and chorioretinopathy with or without mental retardation, 251270
Green Green List (high evidence)
WDR62
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
Phenotypes
  • MCPH
  • primary microcephaly
  • Primary Microcephaly 2 With or Without Cortical Malformations
  • Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317
  • microcephaly cortical malformations and mental retardation (MCMMR), 604317
  • Microcephaly 2, Primary, Autosomal Recessive, With Or Without Cortical Malformations
Green Green List (high evidence)
WDR73
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Galloway-Mowat syndrome, 251300
Green Green List (high evidence)
XRCC4
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • Other
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • Short stature, microcephaly, and endocrine dysfunction, 616541
Green Green List (high evidence)
ZEB2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
Phenotypes
  • Mowat-Wilson syndrome 235730
Amber Amber List (moderate evidence)
CRIPT
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Amber
Phenotypes
  • Short stature with microcephaly and distinctive facies, 615789
Amber Amber List (moderate evidence)
MRE11
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Amber
Phenotypes
  • Nijmegen breakage syndrome-like severe microcephaly
Tags
  • watchlist
Amber Amber List (moderate evidence)
QARS
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Literature
  • UKGTN
  • Expert Review Amber
Phenotypes
  • Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy 615760
Amber Amber List (moderate evidence)
RAD51C
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Amber
Phenotypes
  • Fanconi anemia, complementation group O, 613390
Tags
  • watchlist
Amber Amber List (moderate evidence)
RMI1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Amber
Phenotypes
  • Bloom Syndrome-like Disorder
Tags
  • watchlist
Amber Amber List (moderate evidence)
TAF13
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
  • Literature
Phenotypes
  • Mental retardation, autosomal recessive 60 617432
Tags
  • watchlist
Amber Amber List (moderate evidence)
WDR4
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert list
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
Amber Amber List (moderate evidence)
ZNF335
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Literature
  • Other
  • Expert Review Amber
Phenotypes
  • Autosomal recessive primary microcephaly (MCPH)
  • ?Microcephaly 10, primary, autosomal recessive, 615095
Red Red List (low evidence)
AGMO
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Autosomal recessive primary microcephaly (MCPH)
  • primary microcephaly, developmental delay, short stature and intellectual disability
Red Red List (low evidence)
ANKLE2
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Red
Phenotypes
  • ?Microcephaly 16, primary, autosomal recessive, 616681
Red Red List (low evidence)
ATRIP
1 review
Not set
Sources
  • Other
  • Expert Review Red
  • Expert list
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • severe microcephaly (-10 SD), micrognathia, dental crowding, small earlobes, delayed bone age, and symmetric dwarfism
Red Red List (low evidence)
CDC6
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Other
Phenotypes
  • MPD
  • microcephalic primordial dwarfism
  • ?Meier-Gorlin syndrome 5, 613805
Red Red List (low evidence)
CDK6
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Other
Phenotypes
  • Autosomal recessive primary microcephaly (MCPH)
  • ?Microcephaly 12, primary, autosomal recessive, 616080
Red Red List (low evidence)
CENPE
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert list
Phenotypes
  • ?Microcephaly 13, primary, autosomal recessive, 616051
  • MPD
  • microcephalic primordial dwarfism
Red Red List (low evidence)
DNA2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Red
Phenotypes
  • ?Seckel syndrome 8, 615807
  • SCKL8
Red Red List (low evidence)
EOMES
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • microcephaly syndrome
Red Red List (low evidence)
ERCC5
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Red
Phenotypes
  • Cerebrooculofacioskeletal syndrome 3, 616570 (Microcephaly)
  • Xeroderma pigmentosum, group G/Cockayne syndrome, 278780
Red Red List (low evidence)
FANCM
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Other
Phenotypes
  • Fanconi anemia
Red Red List (low evidence)
NIN
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Red
Phenotypes
  • ?Seckel syndrome 7, 614851
  • SCKL7
Red Red List (low evidence)
NSMCE2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
Phenotypes
  • Seckel syndrome 10, 617253
  • SCKL10
Red Red List (low evidence)
PHC1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Other
  • Expert list
Phenotypes
  • Autosomal recessive primary microcephaly (MCPH)
  • ?Microcephaly 11, primary, autosomal recessive, 615414
  • MCPH
  • primary microcephaly
Red Red List (low evidence)
PLAA
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Red
Phenotypes
  • Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, 617527
Red Red List (low evidence)
PPP1R15B
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
Phenotypes
  • Microcephaly, short stature, and impaired glucose metabolism 2, 616817
  • MSSGM2
Red Red List (low evidence)
SASS6
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Other
Phenotypes
  • autosomal recessive primary microcephaly (MCPH)
  • ?Microcephaly 14, primary, autosomal recessive, 616402
Red Red List (low evidence)
TUBGCP3
1 review
Not set
Sources
  • Expert list
Phenotypes
  • MCPH
  • primary microcephaly
Red Red List (low evidence)
WDFY3
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Other
  • Expert Review Red
Phenotypes
  • ?Microcephaly 18, primary, autosomal dominant, 617520

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