Rare disease due to parents’ genes

Dear Dr. Roach: My 1-year-old grandniece (my brother’s granddaughter) was recently diagnosed with Van der Knaap disease after suffering seizures and getting an MRI. An internet search described it as a rare inherited disorder with walking difficulties and a progressive decline in brain function.

I would appreciate any information about this disease and its course. I am also concerned about its likelihood of affecting my other relatives. Is there any genetic screening they can get to find out their risks?

R.K.

Answer: There are so many rare inherited disorders that it is virtually impossible to know them all. Megalencephalic leukoencephalopathy with subcortical cysts, also called Van der Knapp disease, is most commonly caused by a mutation in one of two separate genes (called MLC1 and HEPACAM). It is passed on as an autosomal recessive disorder, meaning that both parents need to carry a copy of the gene.

Your brother has approximately a 50% chance of being a carrier, and you have a 25% chance of being a carrier. A genetic test can confirm the diagnosis, at which point family members can be screened to see if they carry the gene. A genetic counselor is an essential consultant.

Children with the classic form of the disease usually have large brains and large heads that become more pronounced during the first year of growth. Seizures are common, and the progressive decline in brain function that you mentioned is variable in this condition. But it is generally described as mild. Some of those affected are unable to walk in just a few years, where others continue to walk independently until their 40s at least.

There is also an improving form where the affected children do get better over time.

I wish I could give you a better idea of how your grandniece will do, but this is a rare and recently described condition (1995), for which there is no specific treatment. The seizures are treated and generally well-controlled, similar to any other type of epilepsy.