IUGR and IGF abnormalities (Version 1.69)

Description

IUGR inclusion criteria (29416)
- Height Standard Deviation Score (SDS) <-3 (very significant short stature - well below the 0.4th centile) AND
- At least one of:
  - being born small for gestational (birth weight and/or length <-2SDS), ± a history of intra-uterine growth restriction
  - Body disproportion - e.g. discrepancy between stature and head size, limb to spine disproportion, limb asymmetry
  - Dysmorphic features e.g. facial dysmorphism, polydactyly/syndactyly, ear abnormalities
  - Aberration in the GH-IGF axis (evidence of GH insensitivity or deficiency)
  - Other pituitary hormonal deficiencies
  - Family history (short stature that is explained or idiopathic in parents, affected siblings,cousins) and/or consanguinity
  - Other features such as cleft palate, hearing loss, visual impairment with eye abnormalities including anophthalmia/microphthalmia, optic nerve hypoplasia, retinal dystrophy, forebrain abnormalities and learning difficulties
- For all patients with no abnormalities of the GH-IGF-I axis classified as Idiopathic Short Stature or who are small for gestational age with failure of catch up growth, a skeletal survey should be performed.

IUGR exclusion criteria (29416)
- Acquired causes of short stature, e.g. autoimmune, intracranial neoplasia, infective causes such as Group B Streptococcal meningitis, Langerhans cell Histiocytosis, trauma, previous treatment for malignancy including irradiation, exogenous glucocorticoid use, psychosocial growth failure, chronic disease
- Syndromes associated with short stature such as Turner syndrome, Noonan syndrome, Down syndrome, other chromosomal disorders. However, if the patient has a clinical diagnosis of, e.g. Noonan syndrome, and testing of known genes associated with the syndrome has not identified a pathogenic mutation, then they should be included in the 100000 genomes study. 
- Foetal alcohol syndrome 
- Genetically proven skeletal dysplasias such as hypochondroplasia or achondroplasia
- Genetically proven Silver-Russell syndrome

Prior genetic testing guidance (29416)
- 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.

IUGR prior genetic testing genes (29416)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - All patients with short stature and other features such as developmental delay and dysmorphism should have a DNA microarray with no pathogenic copy number variants detected prior to enrolment
  - Additional genetic testing should have been performed as appropriate

Closing statement (29416)
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

16 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Mehul Dattani (UCL Institute of Child Health)

Group: GeCIP domain
Workplace: Research lab
Peter Clayton (University of Manchester)

Group: GeCIP domain
Workplace: NHS clinical service
Philip Murray (University of Manchester)

Group: GeCIP domain
Workplace: Research lab
Richard Scott (Genomics England Curator)

Group: Other
Workplace: Other
emma baple (Genomics England Curator)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Helen Brittain (Genomics England Curator)

Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

Group: Other NHS organisation
Workplace: NHS diagnostic lab
Dmitrijs Rots (Children's Clinical University Hospital)

Group: Other
Workplace: Research lab
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other
Andžela Lazdāne (Children's Clinical University Hospital of Latvia)

Group: Other
Workplace: Other diagnostic lab

117 Entities

115 reviewed, 97 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 117 Entitiess
Green Green List (high evidence)	AMMECR1	2 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green Literature Phenotypes Short stature Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, 300990 Tags
Green Green List (high evidence)	ANKRD11	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes KBG syndrome 148050 Tags
Green Green List (high evidence)	BLM	5 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Bloom syndrome, OMIM:210900 Tags
Green Green List (high evidence)	BRAF	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Cardiofaciocutaneous syndrome Tags
Green Green List (high evidence)	CBL	1 review	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Other Phenotypes NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MEYLOMONOCYTIC LEUKEMIA Tags
Green Green List (high evidence)	CCDC8	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes 3-M syndrome 3, 614205 Tags
Green Green List (high evidence)	CDC6	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Meier-Gorlin syndrome 5, OMIM:613805 patellar hypoplasia/aplasia, microtia, meier-gorlin syndrome, mammary hypoplasia Tags
Green Green List (high evidence)	CDKN1C	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)	Sources Expert Review Green UKGTN Phenotypes Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies Tags
Green Green List (high evidence)	CDT1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Meier-Gorlin syndrome 4, OMIM:613804 micrognathia, microtia, patellar hypoplasia/aplasia, mammary hypoplasia Tags
Green Green List (high evidence)	CENPJ	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes seckel syndrome Tags
Green Green List (high evidence)	CHD7	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes CHARGE syndrome - ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation CHARGE syndrome, 214800 Tags
Green Green List (high evidence)	CREBBP	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Rubenstein Taybi Tags
Green Green List (high evidence)	CRIPT	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes frontal bossing, high forehead, sparse hair and eyebrows, telecanthus, mild proptosis (staring look), upturned nostrils, and hypoplastic terminal phalanges with brachydactyly Tags
Green Green List (high evidence)	CUL7	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes 3-M syndrome 1, 273750 Tags
Green Green List (high evidence)	DHCR7	4 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Smith Lemli Opitz Tags
Green Green List (high evidence)	EP300	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Rubenstein Taybi Tags
Green Green List (high evidence)	ERCC6	5 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Cockayne syndrome, type B, 133540 Tags
Green Green List (high evidence)	ERCC8	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes cockayne Tags
Green Green List (high evidence)	FANCA	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Literature Phenotypes pre- and postnatal growth retardation malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii) a typical facial appearance with small head, eyes, and mouth hearing loss hypogonadism and reduced fertility cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots) bone marrow failure and susceptibility to cancer, predominantly acute myeloid leukemia. Fanconi Anemia Fanconi anemia, complementation group A, 227650 Fanconi anemia Tags
Green Green List (high evidence)	FANCB	1 review	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 Fanconi anemia Fanconi anemia, complementation group B, 300514 Fanconi Anemia, X-Linked VACTERL Association with Hydrocephalus Tags
Green Green List (high evidence)	FANCC	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Literature Phenotypes pre- and postnatal growth retardation malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii) a typical facial appearance with small head, eyes, and mouth hearing loss hypogonadism and reduced fertility cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots) bone marrow failure and susceptibility to cancer, predominantly acute myeloid leukemia. Fanconi Anemia Fanconi anemia, complementation group C, 227645 Fanconi anemia Tags
Green Green List (high evidence)	FANCD2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Phenotypes Fanconi Anemia Fanconi anemia, complementation group D2, 227646 Fanconi anemia Tags
Green Green List (high evidence)	FANCE	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Phenotypes Fanconi Anemia Fanconi anemia, complementation group E, 600901 Fanconi anemia Tags
Green Green List (high evidence)	FANCF	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Phenotypes Fanconi Anemia Fanconi anemia, complementation group F, 603467 Fanconi anemia Tags
Green Green List (high evidence)	FANCG	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Expert Review Green Literature Phenotypes pre- and postnatal growth retardation malformations of the kidneys, heart, and skeleton (absent or abnormal thumbs and radii) a typical facial appearance with small head, eyes, and mouth hearing loss hypogonadism and reduced fertility cutaneous abnormalities (hyper- or hypopigmentation and cafe-au-lait spots) bone marrow failure and susceptibility to cancer, predominantly acute myeloid leukemia. Fanconi Anemia Fanconi anemia, complementation group G, 614082 Fanconi anemia Fanconi anemia complementation group G Tags
Green Green List (high evidence)	FANCI	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Phenotypes Fanconi Anemia Fanconi anemia, complementation group I, 609053 Fanconi anemia Tags
Green Green List (high evidence)	FANCL	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Green Phenotypes Fanconi Anemia Fanconi anemia, complementation group L, 614083 Fanconi anemia Tags
Green Green List (high evidence)	FGD1	3 reviews 3 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Aarskog Tags
Green Green List (high evidence)	FGF8	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes hypopituitarism, absent corpus callosum, Holoprosencephaly, Moebius syndrome, craniofacial defects, high arched palate, maxillary hypoplasia, microcepahly, spastic diplegia Tags
Green Green List (high evidence)	FGFR1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Tags
Green Green List (high evidence)	GH1	2 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Growth hormone deficiency Tags
Green Green List (high evidence)	GHR	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Laron syndrome Tags
Green Green List (high evidence)	GHRHR	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Growth hormone deficiency Tags
Green Green List (high evidence)	GLI2	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Holoprosencephaly, hypopituitarism Tags
Green Green List (high evidence)	GLI3	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Pallister-Hall syndrome Tags
Green Green List (high evidence)	HDAC8	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 Green Other Phenotypes Cornelia De Lange Tags
Green Green List (high evidence)	HESX1	2 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Growth hormone deficiency with pituitary anomalies, OMIM:182230 Pituitary hormone deficiency, combined, 5, OMIM:182230 Septooptic dysplasia, OMIM:182230 Tags
Green Green List (high evidence)	HRAS	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Costello syndrome Tags
Green Green List (high evidence)	IGF1	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Insulin-like growth factor I deficiency, OMIM:608747 Tags
Green Green List (high evidence)	IGF1R	3 reviews 3 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Insulin-like growth factor I, resistance to, OMIM:270450 Tags
Green Green List (high evidence)	IGFALS	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Acid-labile subunit, deficiency of, OMIM:615961 Short stature Delayed puberty Very low IGF-I levels Tags
Green Green List (high evidence)	INSR	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Leprechaunism Tags
Green Green List (high evidence)	7q11.23 recurrent (Williams-Beuren syndrome) region (includes ELN) Loss ISCA-37392-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes 194050 Williams syndrome Tags
Green Green List (high evidence)	22q11.2 recurrent region (distal region, LCR22-D to LCR22-E or -F) Loss ISCA-37397-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes diaphragmatic hernia mild skeletal abnormalities uterine didelphys 611867 DiGeorge syndrome (DGS) clinodactyly velocardiofacial syndrome ADHD Goldenhar syndrome prematurity developmental delay micropephaly cardiovascular defects Seizures global developmental delay language delay prenatal and postnatal growth delay Hyptonia Tags
Green Green List (high evidence)	16p13.3 region (includes CREBBP) Loss ISCA-37406-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green 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 Tags
Green Green List (high evidence)	17q21.3 recurrent region (includes KANSL1) Loss ISCA-37420-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes Koolen-De Vries syndrome, OMIM:610443 Developmental delay/intellectual disability, hypotonia, distinctive facial features, congenital malformations, and behavioural feature Tags
Green Green List (high evidence)	4p16.3 terminal (Wolf-Hirshhorn syndrome) region Loss ISCA-37429-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes Wolf-Hirschhorn syndrome, OMIM:194190 Tags
Green Green List (high evidence)	KANSL1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Literature Phenotypes Koolen-De Vries syndrome, OMIM:610443 Facial features Delayed psychomotor development Intellectual disability Tags
Green Green List (high evidence)	KDM6A	2 reviews 2 green	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 Expert Review Green Phenotypes Kabuki Tags
Green Green List (high evidence)	KMT2D	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Kabuki syndrome 1, OMIM:147920 Tags
Green Green List (high evidence)	KRAS	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Rasopathy Tags
Green Green List (high evidence)	LHX3	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes GH, TSH, LH, FSH, PRL deficiencies Tags
Green Green List (high evidence)	LHX4	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes hypopituitarism Tags
Green Green List (high evidence)	LIG4	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes LIG4 syndrome, OMIM:606593 microcephaly, growth retardation, immunodeficiency, developmental delay Tags
Green Green List (high evidence)	MAP2K1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Cardiofaciocutaneous syndrome Tags
Green Green List (high evidence)	MAP2K2	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Cardiofaciocutaneous syndrome Tags
Green Green List (high evidence)	NBN	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Nijmegen breakage syndrome Tags
Green Green List (high evidence)	NIPBL	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Cornelia De Lange Tags
Green Green List (high evidence)	NRAS	1 review	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Other Phenotypes A restricted spectrum of NRAS mutations causes Noonan syndrome. (Nat Genet. 42: 27-29, 2010.) Tags
Green Green List (high evidence)	OBSL1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes 3-M syndrome 2, 612921 Tags
Green Green List (high evidence)	ORC1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Meier-Gorlin syndrome 1, OMIM:224690 microtia, beaked nose, patellar aplasia/hypoplasia, mammary hypoplasia, micrognathia Tags
Green Green List (high evidence)	ORC4	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Meier-Gorlin syndrome 2, OMIM:613800 micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia Tags
Green Green List (high evidence)	ORC6	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Meier-Gorlin syndrome 3, OMIM:613803 micrognathia, patellar aplasia/hypoplasia, microtia, mammary hypoplasia Tags
Green Green List (high evidence)	OTX2	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Microcephaly, bilateral anopthalmia, developmental delay, cleft palate Tags
Green Green List (high evidence)	PAPPA2	5 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Proportionate Short Stature, High Circulating IGF-I, IGFBP-3, and ALS, Mild Microcephaly, thin Long Bones and Decreased Bone Mineral Density Tags
Green Green List (high evidence)	PCNT	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720 Tags
Green Green List (high evidence)	PIK3R1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes SHORT syndrome Tags
Green Green List (high evidence)	PITX2	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes AXENFELD-RIEGER SYNDROME Tags
Green Green List (high evidence)	PNPLA6	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Oliver-Mcfarlane syndrome, Trichomegaly, GH deficiency, retinal dystrophy, hypogonadotrophic hypogonadism Tags
Green Green List (high evidence)	POU1F1	2 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Pituitary hormone deficiency, combined or isolated, 1, OMIM:613038 Variable degree of TSH deficiency Tags
Green Green List (high evidence)	PROKR2	2 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes hypopituitarism, Hypoplastic corpus callosum, normal or small anterior pituitary, Club foot, syrinx spinal cord, microcephaly, epilepsy Tags
Green Green List (high evidence)	PROP1	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Pituitary hormone deficiency, combined Tags
Green Green List (high evidence)	PTPN11	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	RAD21	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Other Phenotypes Cornelia De Lange Tags
Green Green List (high evidence)	RAF1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Rasopathy Tags
Green Green List (high evidence)	RBBP8	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes seckel syndrome but with proportionate head/height impairment, cafe au lair macules Tags
Green Green List (high evidence)	RIT1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes Rasopathy Tags
Green Green List (high evidence)	RNPC3	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Pituitary hormone deficiency, combined or isolated, 7, OMIM:618160 Tags
Green Green List (high evidence)	RNU4ATAC	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes MOPD I Tags locus-type-rna-small-nuclear
Green Green List (high evidence)	ROR2	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Robinow syndrome, autosomal recessive, OMIM:268310 Tags
Green Green List (high evidence)	RPL10	1 review 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green Literature Phenotypes Mental retardation, X-linked, syndromic, 35 300998 Tags
Green Green List (high evidence)	RPS6KA3	2 reviews 2 green	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 Expert Review Green Phenotypes Coffin Lowry Tags
Green Green List (high evidence)	SAMD9	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes MIRAGE syndrome, 617053 Tags missense
Green Green List (high evidence)	SHOC2	1 review	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Other Phenotypes Noonan with loss of anagen hair Tags
Green Green List (high evidence)	SHOX	3 reviews 2 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Langer mesomelic dysplasia, OMIM:249700 (PR) Leri-Weill dyschondrosteosis, OMIM:127300 (PD) Short stature, idiopathic familial, OMIM:300582 Tags Pseudoautosomal region 1
Green Green List (high evidence)	SMC1A	2 reviews 2 green	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 Expert Review Green Phenotypes Cornelia de Lange syndrome 2, OMIM:300590 Cornelia de Lange syndrome 2, MONDO:0010370 Tags
Green Green List (high evidence)	SMC3	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Cornelia De Lange Tags
Green Green List (high evidence)	SOS1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Rasopathy Tags
Green Green List (high evidence)	SOX2	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	SOX3	4 reviews 2 green	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 Expert Review Green Phenotypes Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123 Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252 Panhypopituitarism, X-linked, OMIM:312000 Panhypopituitarism, X-linked, MONDO:0010712 Tags
Green Green List (high evidence)	SRCAP	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Floating-Harbor syndrome, 136140 Tags
Green Green List (high evidence)	STAT5B	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	TBCE	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	TRIM37	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Mulibery Nanism Tags
Green Green List (high evidence)	WRN	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Werner syndrome Tags
Green Green List (high evidence)	XRCC4	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Short stature, microcephaly, and endocrine dysfunction, OMIM:616541 Short stature, microcephaly, hypothyroidism, diabetes mellitus, progressive ataxia, hypergonadotrophic hypogonadism Tags
Green Green List (high evidence)	ZFP57	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Phenotypes consistent with hypomethylation at multiple imprinted loci Tags
Amber Amber List (moderate evidence)	ARCN1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber Literature Phenotypes Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay, OMIM:617164 Tags
Red Red List (low evidence)	ACAN	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes short stature, accelerated bone maturation, Spondyloepiphyseal dysplasia, early onset osteoarthritis Tags
Red Red List (low evidence)	ATRIP	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes microcephaly, micrognathia, small ear lobes, dental crowding Tags
Red Red List (low evidence)	ATRX	4 reviews 3 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes SGA, which is sometimes called intrauterine growth restriction (IUGR), Tags
Red Red List (low evidence)	BTK	4 reviews 3 green	Not set	Sources Emory Genetics Laboratory Expert Review Red Tags
Red Red List (low evidence)	DNA2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes seckel syndrome Tags
Red Red List (low evidence)	DOK7	4 reviews 3 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Myasthenia, limb-girdle, familial, 254300Fetal akinesia deformation sequence, 208150 Tags
Red Red List (low evidence)	EPHX1	3 reviews 3 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes ?Fetal hydantoin syndromeDiphenylhydantoin toxicityHypercholanemia, familial, 607748{Preeclampsia, susceptibility to}, 189800 Tags
Red Red List (low evidence)	FANCM	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert review Expert Review Red Phenotypes Fanconi Anemia Fanconi anemia, complementation group M, 614087 Fanconi anemia Tags drug-toxicity
Red Red List (low evidence)	GHSR	2 reviews 2 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Expert Review Red Literature Phenotypes Idiopathic short stature, GH deficiency Tags
Red Red List (low evidence)	GPR161	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Red Literature Phenotypes Short stature with hypopituitarism, intellectual disability, sparse or absent hair in the frontal area, hypotelorism, broad nasal root, thick alae nasi, nail hypoplasia, short fifth finger, 2-3 toe syndactyl. MRI showed hypoplastic pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pituitary stalk Tags
Red Red List (low evidence)	H19	2 reviews	Other - please specifiy in evaluation comments	Sources Expert Review Red Literature Phenotypes Russell-Silver syndrome Tags locus-type-rna-long-non-coding
Red Red List (low evidence)	IFT172	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Red Literature Phenotypes GH deficiency, retinopathy, metaphyseal dysplasia Tags
Red Red List (low evidence)	IGF2	5 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)	Sources Expert Review Expert Review Red Literature Phenotypes Pre- and post-natal growth failure Silver-Russell phenptype IUGR Tags watchlist
Red Red List (low evidence)	LIG1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes immunodeficiency, sun sensitivity, growth reatrdation Tags
Red Red List (low evidence)	MCM5	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes ?Meier-Gorlin syndrome 8 617564 Tags
Red Red List (low evidence)	RAPSN	4 reviews 3 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Fetal Akinesia Deformation Sequence Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency, 608931Myasthenic syndrome, congenital, associated with facial dysmorphism and acetylcholine receptordeficiency, 608931Fetal akinesia deformation sequence, 208150 Tags
Red Red List (low evidence)	SHOX2	2 reviews 2 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Tags
Red Red List (low evidence)	SMARCAL1	2 reviews 2 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Tags
Red Red List (low evidence)	THRB	2 reviews 2 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Tags

Major version comments

07 June 2016: Panel revised according to expert reviews and internal review. Promoted to version 1.

IUGR and IGF abnormalities (Version 1.69)

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