This rare genetic condition is characterized by the presence of abnormalities of the face, genital, head, skin, ear and the heart. The LEOPARD refers to the (L)entigines (the dark spots on the skin), (E)lectrocardiographic conduction defects, (O)cular hypertelorism (wide-spaced eyes), (P)ulmonary stenosis, (A)bnormalities of the genitalia, (R)etarded growth causing short stature and (D)eafness. Leopard syndrome also belongs to a related condition known as RASopathies which are the result of genetic mutations that affects the RAF pathway disrupting the normal growth and development.
Causes
Leopard syndrome develops as the result of the mutation in one of two genes; PTPN11or RAF1. Among most of the affected cases, the genetic mutation in the PTPN11 gene is identified. These genes are essential for the production of proteins that are necessary for the important signaling pathways required for the formation of various tissues. These proteins are also involved in the regulation of cell movement (migration), cell division, and cell differentiation (a process where cells conduct specific functions). This genetic mutation results in the production of the protein that does not function normally affecting their ability to respond to cell signals. Leopard syndrome is inherited in an autosomal dominant pattern meaning a single copy of the mutated gene can cause this disorder. This mutation can either be inherited or can occur as the new genetic changes.
Symptoms
The symptoms vary depending on the case. Some of the symptoms of Leopard syndrome include freckle-like spots on the skin (multiple lentigines), cardiac anomalies such as electrocardiographic conduction defects, varying degrees of heart block, structural malformations of the heart such as hypertrophic obstructive cardiomyopathy, obstruction with the normal flow of blood from the heart to the lungs and abnormality of the pulmonary artery. In addition, they may also have widely spaced eyes (ocular hypertelorism), craniofacial malformations, growth retardation resulting in short stature, skeletal abnormalities, hearing loss and genital abnormalities.
Diagnosis
Leopard Syndrome may be suspected in the newborn infants who present discoloration of the skin with the additional characteristic features. The skin sample may be required which will be observed under the microscope to detect the multiple lentigines. These affected children should also have a periodic cardiac evaluation to identify the heart abnormalities that can develop. Various cardiac assessments will be required including X-ray studies, electrocardiography (EKG) and echocardiography to determine the presence of heart blocks, structural malformations and to determine the effective function of the heart. The genital abnormalities may be detected using various techniques and deficiencies of certain hormones may be identified using laboratory tests. Skeletal abnormalities are detected using X-ray studies and the regular hearing evaluation can identify the potential hearing problems so early treatment can be implemented.
Treatment
The treatment is focused on the specific symptoms that are evident in each individual. In the case of structural abnormality, pulmonary stenosis and hypertrophic obstructive cardiomyopathy, the treatment can include various medications or surgical intervention based on the severity. Hormone replacement may be required for those with delayed puberty and those with hearing loss may be treated with hearing aids or speech therapy. Additional craniofacial or skeletal abnormalities can be treated with corrective surgery.
References
https://rarediseases.org/rare-diseases/leopard-syndrome/
https://ghr.nlm.nih.gov/condition/noonan-syndrome-with-multiple-lentigines#genes