Details of Disease

General Information of Disease (ID: DISBDL4S)

• Disease Name: Microcephaly 6 with or without short stature
• Definition: Disorder of fetal brain growth; individuals have small brains and almost always have mental retardation, although rare individuals with mild microcephaly (-3 SD) and normal intelligence have been reported. Clinical features include the features of microcephaly 6, primary, autosomal recessive?and 'Seckel syndrome', and may include short stature or mild seizures.|Primary microcephaly refers to the clinical finding of a head circumference more than than 3 standard deviations (SD) below the age- and sex-related mean, present at birth. Primary microcephaly is a static developmental anomaly, distinguished from secondary microcephaly, which refers to a progressive neurodegenerative condition. Microcephaly is a disorder of fetal brain growth; individuals with microcephaly have small brains and almost always have mental retardation, although rare individuals with mild microcephaly (-3 SD) and normal intelligence have been reported. Additional clinical features may include short stature or mild seizures. These clinical features include Seckel syndrome, a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (Shanske et al., PMID: 9128935). MCPH is associated with a simplification of the cerebral cortical gyral pattern and a slight reduction in the volume of the white matter, consistent with the small size of the brain, but the architecture of the brain in general is normal, with no evidence of a neuronal migration defect (Woods et al., PMID: 15806441). Seckel syndrome 4 and autosomal recessive primary microcephaly 6 are currently lumped together into one disease entity per the criteria outlined by the ClinGen Lumping and Splitting Working Group, while more published literature detailing Seckel syndrome 4 may support two split disease entities in the future.
• Disease Hierarchy:
  DISZ36SN: Microcephaly with or without short stature
  DISBDL4S: Microcephaly 6 with or without short stature

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CENPJ	OTZCQZN5	Definitive	Autosomal recessive	[1]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.