MILD BRACHMANN-DELANGE SYNDROME - PHENOTYPIC AND DEVELOPMENTAL CHARACTERISTICS OF MILDLY AFFECTED INDIVIDUALS

Since 1981, we have identified 3 patients with mild Brachmann-de Lange syndrome (BDLS) who have had subtle but definite manifestations of the syndrome and mild effects on growth and development. J.G. (B.D. 12/9/72) was first examined at 20 months. He had rather typical craniofacial findings and hirsutism, limitation of full supination of his arms, and brachyclinodactyly of the 5th fingers. IQ was estimated at 65. K.H. (B.D. 10/10/83) was first examined by us at age 9 months and was diagnosed as having ''mild'' BDLS. At age 5, K.H. has demonstrated relatively normal cognitive development (low average-average IQ of 74) with specific learning problems: weakness of visual-motor skills, delayed expressive language development, and articulation difficulties. At age 7, he was attending a regular lst grade classroom, with some special education assistance. M.E.(B.D. 4/19/78) was diagnosed at age 10 years as having ''mild'' BDLS. His physical changes were more subtle than those of the 2 patients above. At age 10, M.E. was in the regular 4th grade classroom receiving special education support. His IQ was in the borderline-low-average range. He had strengths in rote verbal skills, with weaknesses in reading and writing. These 3 patients demonstrate mild BDLS in which characteristic manifestations of the syndrome, particularly craniofacial anomalies, are present and recognizable, but quite subtle, thus making the clinical diagnosis difficult. In addition, the milder physical phenotype is associated with milder cognitive and behavioral consequences. When comparing patients with mild BDLS to those in our practice (4 others) with typical changes, we find that birth weight, absence of major anomalies, and subtlety of craniofacial abnormalities are predictive of mildly affected patients. (C) 1993 Wiley-Liss, Inc.