LEOPARD syndrome is a rare inherited disorder characterized by abnormalities of the skin, the structure and function of the heart, the inner ear, the head and facial area, and/or the genitals. LEOPARD syndrome is nearly always due to mutations in the PTPN11 gene (protein-tyrosine phosphatase, no receptor type 11). It is inherited in an autosomal dominant manner, which means that if one parent is affected there is a 50% chance that each child will be affected. About 70% of cases are inherited. The remainder is sporadic cases occurring from new mutations. The signs and symptoms experienced by people with LEOPARD syndrome vary greatly.
The sign and symptoms of LEOPARD syndrome involve lentigines, electrocardiographic conduction abnormalities, optical hypertelorism, pulmonary stenosis, abnormal genitalia, retarded growth and deafness. Some patients may have a fractional form of the syndrome and suffer mild symptoms while others with the full syndrome are more severely affected. Lentigines may be present at birth or develop during childhood. They become more numerous and darker with age. Other skin lesions, such as nevocellular nevi and malignant melanomas, reported sporadically in the LEOPARD syndrome, may undergo depigmentation.
Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy and pulmonary valve stenosis. Postnatal increase retardation resulting in short size arises in fewer than 50% of affected persons. Sensorineural hearing deficits present in approximately 20% are poorly characterized. Mental retardation, typically mild, is observed in approximately 30% of persons with LS. Antiarrhythmic treatment may be required in cases with life-threatening ventricular ectopy. Treatment of hearing loss includes hearing aids, enrollment in an educational program for the hearing impaired, and consideration of cochlear implantation.
Surgical treatment may be required in cases with harsh outflow tract obstruction or in patients with cryptorchidism, hypospadias, or severe skeletal deformity. Cryosurgery and laser treatment may be beneficial for isolated lentigines. For some patients, treatment with tretinoin cream and hydroquinone cream may be helpful. Therapeutic regimens include beta-adrenergic receptor or calcium channel blocking agents to reduce outflow tract obstruction and adrenergic responsiveness in patients with structural cardiac anomalies. Genetic counseling should be offered to all patients with LEOPARD syndrome.