MedGen

ASPM primary microcephaly (ASPM-MCPH) is characterized by: (1) significant microcephaly (below -3 SD for age) usually present at birth and always present before age one year and (2) the absence of other congenital anomalies. While developmental milestones are usually normal in young children, older children have variable levels of intellectual disability. Neurologic examination is usually normal except for mild spasticity. Seizures are not common. [from GeneReviews]

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. 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 (review by Woods et al., 2005). Most cases of primary microcephaly show an autosomal recessive mode of inheritance. Because MCPH directly affects neurogenesis, or neurogenic mitosis, rather than growth of the skull, some prefer the term 'micrencephaly' (Hofman, 1984). MCPH1 in particular is associated with premature chromosome condensation in cell studies (Darvish et al., 2010). Genetic Heterogeneity of Primary Microcephaly Primary microcephaly is a genetically heterogeneous disorder. See MCPH2 (604317), caused by mutation in the WDR62 gene (613583) on chromosome 19q13; MCPH3 (604804), caused by mutation in the CDK5RAP2 gene (608201) on 9q33; MCPH4 (604321), caused by mutation in the CASC5 gene (609173) on 15q14; MCPH5 (608716), caused by mutation in the ASPM gene (605481) on 1q31; MCPH6 (608393), caused by mutation in the CENPJ gene (609279) on 13q12; MCPH7 (612703), caused by mutation in the STIL gene (181590) on 1p33; MCPH8 (614673), caused by mutation in the CEP135 gene (611423) on 4q12; MCPH9 (614852), caused by mutation in the CEP152 gene (613529) on 15q21; MCPH10 (615095), caused by mutation in the ZNF335 gene (610827) on 20q13; MCPH11 (615414), caused by mutation in the PHC1 gene (602978) on 12p13; MCPH12 (616080), caused by mutation in the CDK6 gene (603368) on 7q21; MCPH13 (616051), caused by mutation in the CENPE gene (117143) on 4q24; MCPH14 (616402), caused by mutation in the SASS6 gene (609321) on 1p21; MCPH15 (616486), caused by mutation in the MFSD2A gene (614397) on 1p34; MCPH16 (616681), caused by mutation in the ANKLE2 gene (616062) on 12q24; MCPH17 (617090), caused by mutation in the CIT gene (605629) on 12q24; MCPH18 (617520), caused by mutation in the WDFY3 gene (617485) on 4q21; MCPH19 (617800), caused by mutation in the COPB2 gene (606990) on 3q23; MCPH20 (617914), caused by mutation in the KIF14 gene (611279) on 1q31; MCPH21 (617983), caused by mutation in the NCAPD2 gene (615638) on 12p13; MCPH22 (617984), caused by mutation in the NCAPD3 gene (609276) on 11q25; MCPH23 (617985), caused by mutation in the NCAPH gene (602332) on 2q11; MCPH24 (618179), caused by mutation in the NUP37 gene (609264) on 12q23; MCPH25 (618351), caused by mutation in the MAP11 gene (618350) on 7q22; MCPH26 (619179), caused by mutation in the LMNB1 gene (150340) on 5q23; MCPH27 (619180), caused by mutation in the LMNB2 gene (150341) on 19p13; MCPH28 (619453), caused by mutation in the RRP7A gene (619449) on 22q13; MCPH29 (620047), caused by mutation in the PDCD6IP gene (608074) on 3p22; and MCPH30 (620183), caused by mutation in the BUB1 gene (602452) on 2q14. [from OMIM]

MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.

People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems.

Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.

Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head." [from MedlinePlus Genetics]

MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.

People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems.

Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.

Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head." [from MedlinePlus Genetics]

CDK13-related disorder, reported in 43 individuals to date, is characterized in all individuals by developmental delay / intellectual disability (DD/ID); nearly all individuals older than age one year display impaired verbal language skills (either absent or restricted speech). Other common findings are recognizable facial features in some individuals, behavioral problems (autism spectrum disorder or autistic traits/stereotypies, attention-deficit/hyperactivity disorder), feeding difficulties in infancy, structural cardiac defects, and seizures. [from GeneReviews]

Reduced size of the cerebral cortex. [from HPO]