IllnessMicrocephaly [patients without Seckel symptoms], differential diagnosis

NGS +

Primary microcephaly (MCPH) is a disorder of brain development that causes occipitofrontal head circumference to be significantly below the mean for (gestational) age and sex. MCPH has many non-genetic causes, while genetic microcephaly/syndromes are relatively rare overall. Genes mutated in microcephaly encode centrosomal proteins (centriole biogenesis) and many different mechanistic categories, especially DNA replication and repair. The severity of developmental delay/intellectual disability appears to correlate with the severity of primary microcephaly. This microcephaly panel is compiled according to the guidelines (see below) and summarizes the relevant genes of several categories. All classical modes of inheritance are observed in microcephaly, but multifactorial events are quite prominent. The diagnosis rates vary between the microcephaly categories and depend primarily on the clinical preliminary examination results. An inconspicuous genetic finding does not mean exclusion of the clinical suspected diagnosis.

Reference: https://www.awmf.org/uploads/tx_szleitlinien/022-028l_S2k_Klassifikation_Diagnostik_Mikrozephalie_2019-11.pdf

• AR primary microcephaly (AGMO)
• Allelic: Aplastic anemia (NBN)
• Allelic: Epilepsy, progressive myoclonic, 9 (LMNB2)
• Allelic: Exudative vitreoretinopathy 7 (CTNNB1)
• Allelic: Leukemia, acute lymphoblastic (NBN)
• Allelic: Leukodystrophy, adult-onset, AD (LMNB1)
• Allelic: Lipodystrophy, partial, acquired, susceptibility to (LMNB2)
• Allelic: Microhydranencephaly (NDE1)
• Allelic: Seckel syndrome 4 (CENPJ)
• Allelic: Seckel syndrome 5 (CEP152)
• Allelic: Ventricular fibrillation, paroxysmal familial, 2 (DPP6)
• Lissencephaly 4, with microcephaly (NDE1)
• Meckel syndrome 12 (KIF14)
• Mental retardation, AD 19 (CTNNB1)
• Mental retardation, AD 33 (DPP6)
• Microcephaly + chorioretinopathy, AR, 1 (TUBGCP6)
• Microcephaly 1, primary, AR (MCPH1)
• Microcephaly 10, primary, AR (ZNF335)
• Microcephaly 12, primary, AR (CDK6)
• Microcephaly 14, primary, AR (SASS6)
• Microcephaly 16, primary, AR (ANKLE2)
• Microcephaly 17, primary, AR (CIT)
• Microcephaly 2, primary, AR, with/-out cortical malformations (WDR62)
• Microcephaly 20, primary, AR (KIF14)
• Microcephaly 21, primary, AR (NCAPD2)
• Microcephaly 22, primary, AR (NCAPD3)
• Microcephaly 25, primary, AR (TRAPPC14)
• Microcephaly 26, primary, AD (LMNB1)
• Microcephaly 27, primary, AD (LMNB2)
• Microcephaly 29, primary, AR (PDCD6IP)
• Microcephaly 3, primary, AR (CDK5RAP2)
• Microcephaly 4, primary, AR (KNL1)
• Microcephaly 5, primary, AR (ASPM)
• Microcephaly 6, primary, AR (CENPJ)
• Microcephaly 7, primary, AR (STIL)
• Microcephaly 8, primary, AR (CEP135)
• Microcephaly 9, primary, AR (CEP152)
• Microcephaly and chorioretinopathy, AR, 2 (PLK4)
• Neurodevelopmental disorder with spastic diplegia + visual defects (CTNNB1)
• Nijmegen breakage syndrome (NBN)