Homosynaptic facilitation occurs when synapses normally involved in pain pathways undergo changes involving receptors on the post-synaptic membrane as well as the molecular pathways activated upon synaptic transmission. Lower pain thresholds of CTTH result from this homosynaptic facilitation. In contrast, heterosynaptic facilitation occurs when synapses not normally involved in pain pathways become involved. Once this occurs innocuous signals are interpreted as painful signals. Allodynia and hyperalgesia of CTTH represent this heterosynaptic facilitation clinically. Stress
In the literature, stress is mentioned as a factor and may be implicated via the adrenal axis. This ultimately results in downstream activation of NMDA receptor activation, NFκB activation, and upregulation of iNOS with subsequent production of NO leading to pain as described above. Diagnosis
With TTH, the physical exam is expected to be normal with perhaps the exception of either pericranial tenderness upon palpation of the cranial muscles, or presence of either photophobia or phonophobia. Classification
The International Headache Societys most current classification system for headache disorders is the International Classification of Headache Disorders 3rd edition (ICHD-3) as of 2018. This classification system separates tension-type headache (TTH) into two main groups: episodic (ETTH) and chronic (CTTH). CTTH is defined as fifteen days or more per month with headache for greater than three months, or one-hundred eighty days or more, with headache per year. ETTH is less than fifteen days per month with headache or less than one-hundred eighty days with headache per year. However, ETTH is further sub-divided into frequent and infrequent TTH.
Cat eye syndrome (CES) or Schmid–Fraccaro syndrome is a rare condition caused by an abnormal extra chromosome, i.e. a small supernumerary marker chromosome. This chromosome consists of the entire short arm and a small section of the long arm of chromosome 22. In consequence, individuals with the cat eye syndrome have three (trisomic) or four (tetrasomic) copies of the genetic material contained in the abnormal chromosome instead of the normal two copies. The prognosis for patients with CES varies depending on the severity of the condition and their associated signs and symptoms, especially when  heart or kidney abnormalities are seen. Signs and symptoms
Unilateral or bilateral iris coloboma (absence of tissue from the colored part of the eyes)
Preauricular pits/tags (small depressions/growths of skin on the outer ears)
Anal atresia (abnormal obstruction of the anus)
Downward-slanting palpebral fissures (openings between the upper and lower eyelids)
Cleft palate
Kidney problems (missing, extra, or underdeveloped kidneys)
Short stature
Scoliosis/skeletal problems
Cardiac defects (such as TAPVR)
Micrognathia (smaller jaw)
Hernias
Biliary atresia
Rarer malformations can affect almost any organ
Intellectual disability – many are intellectually normal; about 30% of CES patients have moderately impaired mental development, although severe intellectual disability is rare.The term "cat eye" syndrome was coined because of the particular appearance of the vertical colobomas in the eyes of some patients, but over half of the CES patients in the literature do not present with this trait. Genetics
The small supernumerary marker chromosome (sSMC) in CES usually arises spontaneously. It may be hereditary and parents may be mosaic for the marker chromosome, but show no phenotypic symptoms of the syndrome.