These have irregular borders and range in size from 1 mm in diameter to café-au-lait spots, several centimeters in diameter. Also, some areas of vitiligo-like hypopigmentation may be observed. Electrocardiographic conduction abnormalities: Generally observed on an electrocardiograph as a bundle branch block. Ocular hypertelorism: Wideset eyes, which lead to a similar facial resemblance between patients. Facial abnormalities are the second highest occurring symptom after the lentigines. Abnormalities also include: broad nasal root, prognathism (protruding lower jaw), or low-set, possibly rotated, ears. Pulmonary stenosis: Narrowing of the pulmonary artery as it exits the heart. Other cardiac abnormalities may be present, including aortic stenosis, or mitral valve prolapse. Abnormal genitalia: usually cryptorchidism (retention of testicles in body) or monorchism (single testicle). In female patients, this presents as missing or single ovaries, much harder by nature to detect. Ultrasound imaging is performed at regular intervals, from the age of 1 year, to determine if ovaries are present. Retarded growth: Slow, or stunted growth. Most newborns with this syndrome are of normal birth weight and length, but will often slow within the first year. Deafness: Sensorineural (nerve deafness).The presence of all of these hallmarks is not needed for a diagnosis. A clinical diagnosis is considered made when, with lentigines present there are 2 other symptoms observed, such as ECG abnormalities and ocular hypertelorism, or without lentigines, 3 of the above conditions are present, with a first-degree relative (i.e. parent, child, sibling) with a clinical diagnosis.
Y279C, T468M, A461T, G464A, and Q510P which seems to be a unique familial mutation, in that all other variants are caused by transition errors, rather than transversion. Treatment
It is suggested that, once diagnosed, individuals be routinely followed by a cardiologist, endocrinologist, dermatologist, and other appropriate specialties as symptoms present. It is recommended that those with the syndrome who are capable of having children seek genetic counseling before deciding to have children. As the syndrome presents frequently as a forme fruste (incomplete, or unusual form) variant, an examination of all family members must be undertaken. As an autosomal dominant trait there is a fifty percent chance with each child that they will also be born with the syndrome. Although fully penetrant, since the syndrome has variable expressivity, one generation may have a mild expression of the syndrome, while the next may be profoundly affected. Once a decision to have children is made, and the couple conceives, the fetus is monitored during the pregnancy for cardiac evaluation. If a gross cardiac malformation is found, parents receive counseling on continuing with the pregnancy. Other management is routine care as symptoms present:
For those with endocrine issues (low levels of thyrotopin [a pituitary hormone responsible for regulating thyroid hormones], follicle stimulating hormone) drug therapy is recommended. For those who are disturbed by the appearance of lentigines, cryosurgery may be beneficial. Due to the large number of lentigines this may prove time-consuming. An alternative treatment with tretinoin or hydroquinone creams may help.