LEOPARD syndrome (LS). Multiple Lentigines syndrome. Cardio-cutaneous syndrome. Moynahan syndrome. Lentiginosis profusa. Progressive Cardiomyopathic Lentiginosis.
Incidence
LEOPARD syndrome is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, the recurrence risk is 50%. LS is a rare condition, but the exact birth prevalence is unknown. Not less than 200 patients have been reported. Prevalence is <1 / 1 000 000.
Clinical Characteristics
LEOPARD syndrome (LS) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. Some individuals with LEOPARD syndrome may also exhibit mild mental retardation, speech difficulties, and/or, in some cases, additional physical abnormalities.
Precipitants
No reported precipitants of crisis. Fatal events occurring in patients with HCM recommend careful risk assessment and prophylaxis against sudden death in patients at risk.
Provocation Tests
None. Full cardiovascular evaluation is needed especially in infants suspected of having this syndrome.
Diagnostic Procedures
Baseline studies at diagnosis should include a complete clinical examination, cardiological, genitourinary and neurological evaluations and hearing assessment. Diagnostic clues for LS are multiple lentigines and cafe-au-lait spots (CLS), hypertrophic cardiomyopathy and deafness. In the absence of lentiginosis, three features in the patient and the presence of an affected close relative are diagnostic. Diagnosis of LS in the first months of age can be clinically suspected in the presence of three main features, including hypertrophic cardiomyopathy (HCM), distinct facial dysmorphisms and cafe-au-lait spots (CLS). Laboratory studies should include molecular analysis of the PTPN11 and RAF1 genes. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. About 5% of LS patients of the reported series do not have PTPN11 or RAF1 mutations.