Primary Microcephaly (MCPH) is a congenital condition characterized by congenital microcephaly at least 4 SD below the age and sex average, accompanied with a normal structure of the brain, except for a 50-60% reduction in surface area of the cerebral cortex. Interestingly, most affected patients have a normal height, weight, karyotype, as well as brain scans. In addition, although affected patients show some degree of mental retardation, no neurological findings like spasticity or cognitive decline are associated with this disorder. Seizures may form part of the clinical spectrum of MCPH. The mental retardation, itself, is of a mild to moderate form. In fact, the early developmental milestones may appear to be normal. It is only the later milestones, such as speech development, that are delayed. Most affected children have fine motor functions, are well-behaved, remain pleasant, and are compliant with instructions. Speech is, however, severely affected; many patients cannot speak more than a few words, and most can only speak simple sentences. Affected children have a characteristic appearance with a thin, backward slanting forehead, and a small chin. Cataract commonly develops in these children and some may develop epilepsy. Among Asian and Arab populations, MCPH is more common than Caucasian populations. Japanese populations show an incidence of 1 affected patient in every 30,000 infants.
Microcephaly can be diagnosed in the prenatal period by analyzing the scans of the fetus. A head circumference 3 SD below the mean raises suspicion. After birth, if this condition is found to be in association with cognitive impairment and the characteristic facies, it is a strong indicator for MCPH1. Microcephaly may also occur in association with several other congenital disorders. However, this is not the primary form of microcephaly. Treatment for MCPH is supportive. Regular eye examinations can take care of the cataract problem. Anticonvulsants are used for controlling seizures, if present.
Wallerman et al. (2003) performed a genome scan on five families from the Netherlands and Jordan, with 14 patients affected by microcephaly. A maximum LOD score of 4.78 was found for marker D1S1660 at the MCPH5 locus. Haplotype analysis suggests that the gene causing microcephaly is located between markers D1S3469 and D1S1660, which excludes the previously reported ASPM gene.
Mikati et al. (1985) described four siblings with a disorder of microcephaly, hypergonadotropic hypogonadism, and short stature, associated with narrow forehead, synophrys, abnormally folded pinnae, micrognathia, early loss of teeth, cubitus valgus, and genua valga. The parents were first cousins, and they, long with three other siblings of the patinets were healthy.
Rajab et al. (2005) estimated the prevalence of commonly diagnosed autosomal recessive diseases in Oman from a hospital-based register in the year 1993 to 2002 and found that Primary Microcephaly was diagnosed in 31 patients, with an observed incidence of 1 in 15,000 births.
Alshehri (2005) studied the pattern and classification of all major congenital anomalies in Asir region between the years 1997 and 2002. Of the total of 691 neonates born with anomalies, 30 were diagnosed with microcephaly. This constituted 16.7% of neonates with central nervous system anomalies.
[Alshehri MA. Pattern of major congenital anomalies in southwestern Saudi Arabia. Bahrain Med Bull. 2005; 27(1)]