ORPHA:2512

Autosomal recessive primary microcephaly

Synonyms: MCPH · Microcephalia vera · Microcephaly vera · True microcephaly

Type: Etiological subtype
Group: Subtype of disorder
Inheritance: Autosomal recessive
Age of onset: Antenatal, Neonatal
Status: active

Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by reduced head circumference at birth with no gross anomalies of brain architecture and variable degrees of intellectual impairment.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	Autosomal recessive primary microcephaly	MCPH · Microcephalia vera · Microcephaly vera · True microcephaly
fr	Microcéphalie primaire autosomique récessive	MCPH · Microcéphalie vraie
de	Mikrozephalie, primäre, autosomal-rezessive	MCPH · Microcephalia vera · Mikrozephalie, echte
es	Microcefalia primaria autosómica recesiva	MCPH · Microcefalia vera · Microcefalia verdadera
it	Microcefalia primitiva autosomica recessiva	MCPH · Microcefalia vera
nl	Autosomaal recessieve primaire microcefalie	Echte microcefalie · MCPH · Microcephalia vera
pt	Microcefalia isolada congénita
pl	Autosomalna recesywna mikrocefalia pierwotna	Małogłowie prawdziwe · MCPH · Mikrocefalia prawdziwa
cs	Autozomálně recesivní primární mikrocefalie	MCPH · Mikrocefalia vera · Mikrocefalie vera · Pravá mikrocefalie
uk	Аутосомно-рецесивна первинна мікроцефалія	MCPH · Microcephalia vera · Microcephalia vera · Справжня мікроцефалія
zh	常染色体隐性遗传小头畸形	真性小脑髓症
tr	Otozomal resesif primer mikrosefali	MCPH · Mikrosefali vera · Gerçek mikrosefali · Mikrosefali vera

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	251200	E		validated
OMIM	603802	BTNT		validated
OMIM	604317	BTNT		validated
OMIM	604321	BTNT		validated
OMIM	604804	BTNT		validated
OMIM	608393	BTNT		validated
OMIM	608716	BTNT		validated
OMIM	612703	BTNT		validated
OMIM	614673	BTNT		validated
OMIM	614852	BTNT		validated
OMIM	615414	BTNT		validated
OMIM	616051	BTNT		validated
OMIM	616080	BTNT		validated
OMIM	616402	BTNT		validated
OMIM	616486	BTNT		validated
OMIM	616681	BTNT		validated
OMIM	617090	BTNT		validated
OMIM	617432	BTNT		validated
OMIM	617800	BTNT		validated
OMIM	617914	BTNT		validated
OMIM	617983	BTNT		validated
OMIM	617984	BTNT		validated
OMIM	617985	BTNT		validated
OMIM	618179	BTNT		validated
OMIM	618351	BTNT		validated
OMIM	618665	BTNT		validated
OMIM	619453	BTNT		validated
OMIM	620047	BTNT		validated
OMIM	620183	BTNT		validated
ICD-10	Q02	NTBT	attributed	validated
ICD-11	LA05.0	NTBT	attributed	validated
MONDO	0016660	E		validated
MeSH	C579935	E		validated
UMLS	C3711387	E		validated
GARD	12117	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:93890Rare developmental defect during embryogenesis

Parents in the classifications (5):

ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases
ORPHA:199642Isolated congenital microcephaly
rare developmental anomalies during embryogenesis; rare genetic diseases; rare neurological diseases
ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases
ORPHA:522508Rare genetic ophthalmic disorder with cortical involvement
rare genetic diseases
ORPHA:519343Rare ophthalmic disorder with cortical involvement
rare ophthalmic disorders

No children.

Codes that Orphanet moved or referred to this one:

ORPHA:52183Premature chromosome condensation with microcephaly and intellectual disability moved to · inactive

Genes

29 direct

Gene	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
MFSD2A	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:25897	ENSG00000168389	614397	1p34.2	MFSD2 lysolipid transporter A, lysophospholipid	26005865[PMID]_26005868[PMID]
ANKLE2	Disease-causing germline mutation(s) in	Assessed	HGNC:29101	ENSG00000176915	616062	12q24.33	ankyrin repeat and LEM domain containing 2	25259927[PMID]
ASPM	Disease-causing germline mutation(s) in	Assessed	HGNC:19048	ENSG00000066279	605481	1q31.3	assembly factor for spindle microtubules
CDK5RAP2	Disease-causing germline mutation(s) in	Assessed	HGNC:18672	ENSG00000136861	608201	9q33.2	CDK5 regulatory subunit associated protein 2
CDK6	Disease-causing germline mutation(s) in	Assessed	HGNC:1777	ENSG00000105810	603368	7q21.2	cyclin dependent kinase 6	23918663[PMID]
CENPE	Disease-causing germline mutation(s) in	Assessed	HGNC:1856	ENSG00000138778	117143	4q24	centromere protein E	24748105[PMID]
CEP135	Disease-causing germline mutation(s) in	Assessed	HGNC:29086	ENSG00000174799	611423	4q12	centrosomal protein 135
CEP152	Disease-causing germline mutation(s) in	Assessed	HGNC:29298	ENSG00000103995	613529	15q21.1	centrosomal protein 152
CIT	Disease-causing germline mutation(s) in	Assessed	HGNC:1985	ENSG00000122966	605629	12q24.23	citron rho-interacting serine/threonine kinase	27453578[PMID]
COPB2	Disease-causing germline mutation(s) in	Assessed	HGNC:2232	ENSG00000184432	606990	3q23	coat protein complex I subunit beta 2	29036432[PMID]
CPAP	Disease-causing germline mutation(s) in	Assessed	HGNC:17272	ENSG00000151849	609279	13q12.12-q12.13	centrosome assembly and centriole elongation protein
KIF14	Disease-causing germline mutation(s) in	Assessed	HGNC:19181	ENSG00000118193	611279	1q32.1	kinesin family member 14	28892560[PMID]
KNL1	Disease-causing germline mutation(s) in	Assessed	HGNC:24054	ENSG00000137812	609173	15q15.1	kinetochore scaffold 1
MCM7	Disease-causing germline mutation(s) in	Assessed	HGNC:6950	ENSG00000166508	600592	7q22.1	minichromosome maintenance complex component 7	34059554[PMID]
MCPH1	Disease-causing germline mutation(s) in	Assessed	HGNC:6954	ENSG00000147316	607117	8p23.1	microcephalin 1
METTL5	Disease-causing germline mutation(s) in	Assessed	HGNC:25006	ENSG00000138382	618628	2q31.1	methyltransferase 5, N6-adenosine	31564433[PMID]
NCAPD3	Disease-causing germline mutation(s) in	Assessed	HGNC:28952	ENSG00000151503	609276	11q25	non-SMC condensin II complex subunit D3	27737959[PMID]
NUP37	Disease-causing germline mutation(s) in	Assessed	HGNC:29929	ENSG00000075188	609264	12q23.2	nucleoporin 37	30179222[PMID]
PDCD6IP	Disease-causing germline mutation(s) in	Assessed	HGNC:8766	ENSG00000170248	608074	3p22.3	programmed cell death 6 interacting protein	32286682[PMID]
PHC1	Disease-causing germline mutation(s) in	Assessed	HGNC:3182	ENSG00000111752	602978	12p13.31	polyhomeotic homolog 1
PYCR2	Disease-causing germline mutation(s) in	Assessed	HGNC:30262	ENSG00000143811	616406	1q42.12	pyrroline-5-carboxylate reductase 2	27860360[PMID]
SARS1	Disease-causing germline mutation(s) in	Assessed	HGNC:10537	ENSG00000031698	607529	1p13.3	seryl-tRNA synthetase 1	35790048[PMID]
SASS6	Disease-causing germline mutation(s) in	Assessed	HGNC:25403	ENSG00000156876	609321	1p21.2	SAS-6 centriolar assembly protein	24951542[PMID]
STIL	Disease-causing germline mutation(s) in	Assessed	HGNC:10879	ENSG00000123473	181590	1p33	STIL centriolar assembly protein
TAF13	Disease-causing germline mutation(s) in	Assessed	HGNC:11546	ENSG00000197780	600774	1p13.3	TATA-box binding protein associated factor 13	28257693[PMID]
TRAPPC10	Disease-causing germline mutation(s) in	Assessed	HGNC:11868	ENSG00000160218	602103	21q22.3	trafficking protein particle complex subunit 10	35298461[PMID]
TRAPPC14	Disease-causing germline mutation(s) in	Assessed	HGNC:25604	ENSG00000146826	618350	7q22.1	trafficking protein particle complex subunit 14	30715179[PMID]
WARS1	Disease-causing germline mutation(s) in	Assessed	HGNC:12729	ENSG00000140105	191050	14q32.2	tryptophanyl-tRNA synthetase 1	35790048[PMID]
WDR62	Disease-causing germline mutation(s) in	Assessed	HGNC:24502	ENSG00000075702	613583	19q13.12	WD repeat domain 62

Prevalence and incidence

3 records

Type	Class	Value	Area	Qualification	Validation	Source
Annual incidence	1-9 / 1 000 000	0.1 / 100 000	Specific population	Value and class	Validated	21668957[PMID]
Point prevalence	Unknown	—	Worldwide	Class only	Not yet validated	ORPHANET
Annual incidence	1-9 / 100 000	1 / 100 000	Pakistan	Value and class	Validated	21668957[PMID]

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

17 annotations · validated 2016-06-01

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0001263	Global developmental delay
HP:0002282	Gray matter heterotopia
HP:0001510	Growth delay
HP:0010864	Intellectual disability, severe
HP:0000252	Microcephaly
HP:0004322	Short stature
HP:0000340	Sloping forehead
HP:0000219	Thin upper lip vermilion
HP:0000582	Upslanted palpebral fissure
Frequent (79-30%)
HP:0003103	Abnormal cortical bone morphology
HP:0001274	Agenesis of corpus callosum
HP:0001347	Hyperreflexia
HP:0007333	Hypoplasia of the frontal lobes
HP:0001302	Pachygyria
HP:0000122	Unilateral renal agenesis
HP:0002119	Ventriculomegaly
HP:0000076	Vesicoureteral reflux

Run the differential on the 9 obligate / very frequent terms

Annotation source: 11857108[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/2512
This record as JSON: /data/d/2512.json