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Autosomal dominant primary microcephaly

MedGen UID:: 66319
•Concept ID:: C0220693
•: Disease or Syndrome

Synonyms:	Microcephaly autosomal dominant; Microcephaly with autosomal dominant inheritance
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Monarch Initiative:	MONDO:0007988
OMIM®:	156580
Orphanet:	ORPHA2514

Definition

Microcephaly strictly means abnormally small head size, but usually refers to an occipitofrontal head circumference below -2 SD from the mean for the infant's gestational age, sex, and ethnic origin. Microcephaly may appear as an isolated trait or in association with other malformations. It may also be sporadic or familial. Some familial cases are autosomal dominant, but most appear to be recessive (see 251200) (summary by Merlob et al., 1988). [from OMIM]

Clinical features

From HPO

Broad thumb

MedGen UID:: 140880
•Concept ID:: C0426891
•: Finding

Increased thumb width without increased dorso-ventral dimension.

See: Feature record | Search on this feature

Broad hallux

MedGen UID:: 401165
•Concept ID:: C1867131
•: Finding

Visible increase in width of the hallux without an increase in the dorso-ventral dimension.

See: Feature record | Search on this feature

Short stature

MedGen UID:: 87607
•Concept ID:: C0349588
•: Finding

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

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Protruding ear

MedGen UID:: 343309
•Concept ID:: C1855285
•: Finding

Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).

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Microcephaly

MedGen UID:: 1644158
•Concept ID:: C4551563
•: Finding

Head circumference below 2 standard deviations below the mean for age and gender.

See: Feature record | Search on this feature

Increased overbite

MedGen UID:: 539656
•Concept ID:: C0266063
•: Disease or Syndrome

Maxillary teeth cover the mandibular teeth when biting to an increased degree. The feature is defined as a vertical overlap of the maxillary incisors over the mandibular incisors that exceeds 2 mm.

See: Feature record | Search on this feature

Upslanted palpebral fissure

MedGen UID:: 98390
•Concept ID:: C0423109
•: Finding

The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.

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Small forehead

MedGen UID:: 336888
•Concept ID:: C1845250
•: Finding

The presence of a forehead that is abnormally small.

See: Feature record | Search on this feature

Sloping forehead

MedGen UID:: 346640
•Concept ID:: C1857679
•: Finding

Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.

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Alternating esotropia

MedGen UID:: 57515
•Concept ID:: C0152205
•: Disease or Syndrome

Esotropia in which either eye may be used for fixation.

See: Feature record | Search on this feature

Horizontal nystagmus

MedGen UID:: 124399
•Concept ID:: C0271385
•: Disease or Syndrome

Nystagmus consisting of horizontal to-and-fro eye movements.

See: Feature record | Search on this feature

Hypotelorism

MedGen UID:: 96107
•Concept ID:: C0424711
•: Finding

Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).

See: Feature record | Search on this feature

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Abnormality of head or neck
Abnormality of limbs
- Broad hallux
- Broad thumb
Abnormality of the ear
- Protruding ear
Abnormality of the eye
Abnormality of the musculoskeletal system
- Microcephaly
Growth abnormality
- Short stature

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVAutosomal dominant primary microcephaly

Developmental disorder
- Neurodevelopmental disorder
  - Developmental disorder
    - Neurodevelopmental disorder
      - Brain Development Abnormality
        Isolated congenital microcephaly
        Autosomal dominant primary microcephaly

Follow this link to review classifications for Autosomal dominant primary microcephaly in Orphanet.

Recent clinical studies

Etiology

Genetic susceptibility of vitamin D receptor gene polymorphisms on autosomal recessive primary microcephaly patients in Pakistani population: a case-control and in-silico study.

Aslam K, Anjum I, Aslam K, Haq R, Bashir R
Mol Biol Rep 2023 Oct;50(10):8049-8059. Epub 2023 Aug 4 doi: 10.1007/s11033-023-08681-1. PMID: 37541996

Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2.

Zarate YA, Bosanko KA, Thomas MA, Miller DT, Cusmano-Ozog K, Martinez-Monseny A, Curry CJ, Graham JM Jr, Velsher L, Bekheirnia MR, Seidel V, Dedousis D, Mitchell AL, DiMarino AM, Riess A, Balasubramanian M, Fish JL, Caffrey AR, Fleischer N, Pierson TM, Lacro RV
Clin Genet 2021 Apr;99(4):547-557. Epub 2021 Jan 13 doi: 10.1111/cge.13912. PMID: 33381861

De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity.

Cristofoli F, Moss T, Moore HW, Devriendt K, Flanagan-Steet H, May M, Jones J, Roelens F, Fons C, Fernandez A, Martorell L, Selicorni A, Maitz S, Vitiello G, Van der Hoeven G, Skinner SA, Bollen M, Vermeesch JR, Steet R, Van Esch H
Am J Hum Genet 2020 Oct 1;107(4):753-762. Epub 2020 Sep 9 doi: 10.1016/j.ajhg.2020.08.015. PMID: 32910914 Free PMC Article

Activated PI3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature.

Olbrich P, Lorenz M, Cura Daball P, Lucena JM, Rensing-Ehl A, Sanchez B, Führer M, Camacho-Lovillo M, Melon M, Schwarz K, Neth O, Speckmann C
Pediatr Allergy Immunol 2016 Sep;27(6):640-4. Epub 2016 May 27 doi: 10.1111/pai.12585. PMID: 27116393

Ocular abnormalities of true microcephaly.

Alzial C, Dufier JL, Aicardi J, de Grouchy J, Saraux H
Ophthalmologica 1980;180(6):333-9. doi: 10.1159/000308996. PMID: 6777726

See all (5)

Diagnosis

10q23.31 microduplication encompassing PTEN decreases mTOR signalling activity and is associated with autosomal dominant primary microcephaly.

Oliveira D, Leal GF, Sertié AL, Caires LC Jr, Goulart E, Musso CM, Oliveira JRM, Krepischi ACV, Vianna-Morgante AM, Zatz M
J Med Genet 2019 Aug;56(8):543-547. Epub 2018 Oct 9 doi: 10.1136/jmedgenet-2018-105471. PMID: 30301738

A novel ERCC6 splicing variant associated with a mild Cockayne syndrome phenotype.

Swartz JM, Akinci A, Andrew SF, Siğirci A, Hirschhorn JN, Rosenfeld RG, Dauber A, Hwa V
Horm Res Paediatr 2014;82(5):344-52. Epub 2014 Nov 1 doi: 10.1159/000368192. PMID: 25376329 Free PMC Article

See all (2)

Therapy

Activated PI3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature.

See all (1)

Prognosis

A novel ERCC6 splicing variant associated with a mild Cockayne syndrome phenotype.

Swartz JM, Akinci A, Andrew SF, Siğirci A, Hirschhorn JN, Rosenfeld RG, Dauber A, Hwa V
Horm Res Paediatr 2014;82(5):344-52. Epub 2014 Nov 1 doi: 10.1159/000368192. PMID: 25376329 Free PMC Article

See all (1)

Clinical prediction guides

Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2.

Activated PI3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature.

A novel ERCC6 splicing variant associated with a mild Cockayne syndrome phenotype.

Swartz JM, Akinci A, Andrew SF, Siğirci A, Hirschhorn JN, Rosenfeld RG, Dauber A, Hwa V
Horm Res Paediatr 2014;82(5):344-52. Epub 2014 Nov 1 doi: 10.1159/000368192. PMID: 25376329 Free PMC Article

Human ASPM participates in spindle organisation, spindle orientation and cytokinesis.

Higgins J, Midgley C, Bergh AM, Bell SM, Askham JM, Roberts E, Binns RK, Sharif SM, Bennett C, Glover DM, Woods CG, Morrison EE, Bond J
BMC Cell Biol 2010 Nov 2;11:85. doi: 10.1186/1471-2121-11-85. PMID: 21044324 Free PMC Article

See all (4)

MedGen

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Autosomal dominant primary microcephaly

Definition

Clinical features

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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