Claude Shannon and the U-shaped Information Content of developmental phenotypes

Spüre die Welt. This is the second post in our “phenotypic atomism series”, trying to explain how we can gauge the amount of information that phenotypes provide. However, let me start by going very far back. As a graduation gift, my high school teachers gave me a book that set me on the path of becoming a neuroscientist – the User Illusion by Tor Nørretranders, a book that has a more poetic title in its German translation (“Perceive the world”). This book examined the inner workings of human consciousness and explored how our human brains process information. Now, more than 20 years later, I am encountering the idea of measuring information again when trying to understand what phenotypic information is meaningful and how we can assess this. This is a blog post on how we can describe the value of phenotypic information, the importance of time, and how we slowly chip away at the mystery of developmental phenotypes. To put it differently: “Show me the longitudinal information content (IC) for absence seizures – it is going to be U-shaped and you have 60 min.” Continue reading

CHD2 myoclonic encephalopathy – delineating a novel disease

CHD2. In 2013, mutations in CHD2 were reported in various publications including two major studies on epileptic encephalopathies, reinforcing the notion that de novo mutations in this gene are a recurrent cause of epileptic encephalopathies. However, large-scale studies often cannot fully appreciate the complete phenotype of the patient behind the gene finding. Therefore, it is difficult to appreciate similarities between patients and assess whether phenotypes constitute a recognizable entity. In a recent publication in Neurology, the phenotype of CHD2 encephalopathy is explored in detail – it represents a distinct, recognizable disease entity. Continue reading

CACNA2D2, the ducky mouse, and what it takes to be an epilepsy gene

Subunit. Spontaneous mouse mutants help to identify candidate genes for disease mechanisms and have hinted at an important role for ion channels in epilepsy long before the first human channelopathies were identified. The ducky mouse has absence seizures and suffers from ataxia. A truncation mutation in CACNA2D2 could be identified in this phenotype, encoding for an auxiliary calcium channel subunit. This finding emphasizes the role of calcium channels in absence seizures and begs the question whether genetic variation in CACNA2D2 is also involved in human epilepsy. A recent publication in PLOS One now identifies the second recessive CACNA2D2 mutation in a patient with epileptic encephalopathy. But are two independent cases sufficient anymore to claim causality? Continue reading

Traveling with Lennox – the petit mal triad

Lights on and lights out. Staring spells, petits mals, pyknolepsy and absence seizures. The brief spells that occur in patients with epilepsy have riddled neurologists for centuries. This became clear to me when Zaid Afawi and myself saw an epilepsy family in the West Bank on Sunday. When are staring spells epileptic and what kind of seizures are they? For me, this was a good opportunity to read Lennox’s thoughts on this. Eventually, after a long day under the Middle Eastern sun, I fell asleep over the chapter on absence status. Continue reading