Genetic basis: mutation of PTPN11 on chromosome 12q22-qter
Inheritance: autosomal dominant
LEOPARD phenotypic features:
(1) Lentigenes, multiple
(2) Electrocardiographic conduction abnormalities
(3) Ocular hypertelorism
(4) Pulmonary stenosis
(5) Abnormal genitalia (unilateral gonadal agenesis/hypoplasia, hypogonadism)
(6) Retarded growth
(7) Deafness, sensorineural
ECG changes:
(1) abnormal P waves
(2) prolonged PR interval
(3) incomplete bundle branch block or complete heart block
(4) isolated ventricular ectopic beats or ventricular fibrillation
(5) bradycardia
(6) paroxysmal atrial fibrillation
(7) infarction or ischemic pattern
(8) QT prolongation
Other features:
(1) hypertrophic obstructive cardiomyopathy or ventricular septal defect
(2) low set, posteriorly rotated ears
(3) winged scapula
(4) pectus excavatum or carinatum
(5) scoliosis or kyphoscoliosis
(6) broad, flat nose
(7) mild learning disability
(8) genitourinary abnormalities in males (cryptorchidism, hypospadias, unilateral renal hypoplasia or agenesis)
(9) CNS abnormalities (nystagmus, seizures, cerebral atrophy, Arnold-Chiari malformation, agenesis of the corpus callosum)
(10) fusion of cervical spine
(11) restrictive lung disease
(12) orofacial or dental abnormalities (micrognathia, supernumerary teeth, mandibular prognathism, other)
(13) endocrine abnormalities (short stature, hypothyroidism, delayed puberty)
Differential diagnosis:
(1) Noonan syndrome (associated with mutation at PTPN11)
(2) Carney's complex
