KSC2 is present at birth (congenital) and low birth weight may be one of the first symptoms. This extremely rare genetic disorder is characterized by abnormalities affecting the skeleton, the head, and the eyes. Recurrent episodes of unusually low levels of calcium (hypocalcemia) in the blood are common. Most affected individuals, exhibit Short stature of adult height ranging from 48 to 59 inches. Intelligence is usually normal.
KCS2 usually affects several bones of the body. Affected individuals may have thickened outer layers (cortexes) of various long bones, and abnormally thin marrow cavities (medullary stenosis). Some individuals may also have abnormal hardening of some bones (osteosclerosis).
KCS2 also affects the head and face. The anterior fontanel is a soft, membrane-covered area between the bones of an infant’s skull that usually closes about 18 months after birth. However, in KCS2, the anterior fontanel is abnormally large, closes late, and a fibrous joint between the bones in the forehead (metopic suture) is spaced wider than usual. As a result, affected infants have an abnormally large head circumference (macrocephaly) with a prominent forehead.
Several abnormalities of the eyes are also associated with KCS2. Affected individuals may have unusually small eyes (microphthalmia), leakage of cerebrospinal fluid into the optic disk of the eye may cause Swelling of the disk (papilledema), and/or farsightedness (hyperopia). In some cases of this disorder, nearsightedness (myopia) has been observed. One case reported in the medical literature noted retinal and corneal calcification. Another case had bilateral optic atrophy.
Episodes of abnormally low levels of calcium in the blood (hypocalcemia) are prevalent in individuals, especially infants, affected by KCS2. Onset of hypocalcemia is usually within two to three months after birth. Other episodes may occur in relation to stress or may follow surgery or illness in an adult. Hypocalcemia is not permanent (transient) and may be caused by insufficient production of parathyroid hormones (hypoparathyroidism). These hormones, along with vitamin D and the hormone calcitonin, regulate the levels of calcium in the blood. The lack of the parathyroid hormones may be due to improper function or absence of the parathyroid glands in people with KCS2. Symptoms of hypoparathyroidism include weakness, muscle cramps; excessive nervousness; loss of memory; headaches, and abnormal sensations such as tingling, burning, and Numbness of the hands. (For more information about “Hypoparathyroidism,” please see the Related Disorders section of this report.)
Low levels of calcium in the blood may also cause a condition called tetany, which is characterized by muscle cramps and periods of high-pitched respiration (stridor). Individuals with KCS2 may also exhibit abnormally low levels of phosphates in the blood (hypophosphatemia), low levels of a hormone that acts to reduce the blood level of calcium (calcitonin), low levels of circulating red blood cells (anemia), and seizures.
People affected by the recessive form of KCS2 have most of the above-mentioned abnormalities and symptoms. They may also exhibit liver disease during the first month of life (neonatal period), abnormally low levels of a certain type of white blood cell (neutropenia), improper function of another type of white blood cell (T-cells), and/or underdeveloped (hypoplastic), malformed nails.