Familial occurrence of the LEOPARD syndrome.

Abstract

Case 1 A 10‐year‐old boy was admitted to the Neurology Department at the Child's Health Center in Warsaw, Poland, for a diagnosis of mental retardation. Since infancy, small, dark brown, irregularly shaped macules, varying in size from pinpoint to 5 mm in diameter, had been observed on the face, the sclerae, and the neck (Fig. 1).He was born full‐term by spontaneous delivery after uncomplicated pregnancy. The birth weight was 3000 g. The Apgar score was 5 at the first minute. In the first hours after delivery, the infant demonstrated peripheral cyanosis. A heart murmur, graded 3/6 according to the Levine scale, was heard. Chest roentgenogram revealed the enlargement of both heart ventricles. Electrocardiography and echocardiography carried out several times in the first 3 years of life were within normal limits. His psychomotor development was delayed—he sat at 1 year and walked at 2 years of age. There was no history of epileptic seizures.At admission, multiple lentigines on the face and neck were seen. There was a slight disproportion between his height (50–75 percentile) and weight (10–25 percentile). The boy demonstrated poor skeletal muscle development with scoliosis, pectus carinatum, and winged scapulae. Neurologic status was normal, except for slight mental retardation (IQ = 63, according to Wechsler's Intelligence Scale). No cardiac murmur was appreciated at that time. Ophthalmologic examination, audiogram, and electroencephalography were within normal limits. Computerized tomography revealed no brain abnormalities. There was abnormal repolarization on electrocardiography, but echocardiography remained normal.The family was composed of two natural parents, two brothers, and three sisters. Both parents were alive and well. The father did not reside with the family and was unavailable for examination. No lentigines were observed by the mother on his skin. Examination of the mother did not reveal significant skin findings. She had a history of progressive loss of vision in the right eye from very early childhood. She had this eyeball removed at 18 years of age. She had not reported epileptic seizures. Her mental status was normal. The younger brother had a congenital cataract of the left eye and amblyopia. Ultrasonography of the eyeball revealed the presence of arteria hyaloidea persistens. He did not demonstrate lentigines on the skin. His psychomotor development so far is normal. He is now 6 years old. The youngest sister is 10 years old. She has no skin features of the LEOPARD syndrome. Her development is normal. Features of the LEOPARD syndrome have been found in the other siblings, as delineated below. Case 2 Multiple lentigines on the face and neck were found in the middle sister. She had been born after uneventful pregnancy with a weight of 2800 g. Since early childhood, her physical and mental development was delayed. At 18 months, her weight was 8650 g. At 7 years, during routine pediatric examination, a heart murmur was evident. Except for this observation and pectus excavatum, a careful cardiologic examination, electrocardiography and echocardiography were normal; the murmur was regarded as innocent. At 10 years of age, her height and weight remained between the 10th and 25th percentile. Her neurologic status was normal, but psychologic examination found slight mental retardation (IQ = 57). There was no history of epilepsy. Electroencephalography was normal. At 17 years of age she had several syncopal attacks. Admitted to the regional hospital, she died, with death attributed to probable acute cardiopulmonary insufficiency. Case 3 The oldest sister was born at term after uneventful pregnancy. Her birth weight was 2550 g. There were no lentigines seen on her skin. Since early childhood, slight mental retardation has been observed. At 9 years of age, she was admitted to the Cardiology Department because of signs of cardiac insufficiency. At admission, her weight and height were very low (between the 3rd and 10th percentile). Pectus excavatum was seen. She had a tachycardia of 160/min and hepatosplenomegaly. There was a heart murmur, graded 3/6 by the Levine scale, and enlargement of the whole heart on chest roentgenogram. A large tumor in the left cardiac atrium was diagnosed and subsequently resected. Histologically, a cardiac myxoma was diagnosed. The postoperative period was uneventful. At 13 years of age, she underwent a second operation because of tumor regrowth. She demonstrated slight mental retardation with an IQ of 67. Electroencephalography was abnormal with slow activity in the frontal lobes. There was no history of epilepsy. Presently, she is without cardiac symptoms. Her mental status has not changed.