MACROCEPHALY PANEL

Overview

Macrocephaly can have many different causes. In addition to the benign familial form, there are secondary forms caused by hydrocephalus, tumors, or other intracranial processes. Megalencephaly can also be a cause and is often due to rare genetic diseases such as lysosomal storage disorders or leukodystrophies. If imaging techniques and/or metabolic tests do not provide an explanation, exome sequencing can contribute to the diagnosis, especially in cases of developmental disorders.

Symptoms

Macrocephaly is defined as a fronto-occipital head circumference above the 97^th percentile.

Cause

It can have a variety of causes. A distinction is made between an asymptomatic familial form (known as benign macrocephaly) and secondary forms resulting from hydrocephalus or other space-occupying intracranial processes such as tumors, hygromas or hematomas. Isolated thickening of the calvarium (skull) is rare.

In most other cases, the underlying cause may be megalencephaly of varying severity, which in turn can have a wide variety of causes. After ruling out the above-mentioned secondary causes, rare genetic diseases can be considered. These include lysosomal storage diseases, leukodystrophies, such as Alexander's disease, organic or amino acid metabolism disorders, such as glutaric aciduria or Canavan disease, as well as other syndromic diseases, such as overgrowth syndromes.

If the usual investigations using imaging techniques and/or metabolic tests do not reveal a cause, genetic testing using whole exome sequencing (WES) can help to determine the cause, especially if there is also a developmental disorder.

References

Orrù et al. 2018, Am J of Roentgenol. 210:848 / Chitkara et al. 2016, InnovAiT 10:1 / Klein et al. 2013, Autism Res. 6:51 / Williams et al. 2008, Am J Hum Genet. 146A:2023