Severe microcephalyGene: ATRX
Comment on mode of inheritance: X-linked dominant inheritance for Alpha-thalassemia/mental retardation syndrome, 301040 and X-linked recessive inheritance for Mental retardation-hypotonic facies syndrome, X-linked, 309580, both of which include Microcephaly. Therefore MOI recorded as 'XLD' as default.
9 Feb 2017, 9:35 a.m.
Confirmed DD-G2P gene for both Mental retardation-hypotonic facies syndrome, X-linked, 309580 and Alpha-thalassemia/mental retardation syndrome, 301040 (both of which can present with microcephaly).
7 Feb 2017, 10:13 a.m.
Comment on list classification: Updated rating from Red to Green: 1 Expert green review plus >3 cases of ATRX mutations causing both MIM:309580 and MIM:301040.
7 Feb 2017, 10:12 a.m.
not always that dysmorphic
6 Feb 2017, 5 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
Mode of inheritance for ATRX was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
This gene has been classified as Green List (High Evidence).
Phenotypes for gene ATRX were set to Mental retardation-hypotonic facies syndrome, X-linked, 309580 (Microcephaly); Alpha-thalassemia/mental retardation syndrome, 301040 (Microcephaly)
ATRX was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other
ATRX was created by rfoulger