Clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome

Abstract

In a clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome (PLWS) (23 males and 16 females ranging in age from 2 weeks to 39 years), an interstitial deletion of chromosome 15 (breakpoints q11 and q13) was identified in 21 cases and apparently normal chromosomes in the remainder. Studies of parental chromosome 15 variants showed that the del[15q] was paternal in origin, although chromosomes of both parents were normal. All chromosome deletions were de novo events. Possible causes for the chromosome deletion and the role of chromosome rearrangements in individuals with PLWS are discussed. Clinical characteristics of the deletion and nondeletion groups were recorded and compared with 124 individuals reported in the literature. Individuals with the chromosome deletion were found to have lighter hair, eye, and skin color, greater sun sensitivity, and higher intelligence scores than individuals with normal chromosomes. Correlation studies of metacarpophalangeal pattern profile variables and dermatoglyphic findings indicate apparent homogeneity of the deletion group and heterogeneity of individuals with PLWS and normal chromosomes.

Fig. 1

Age at achievement of developmental stages of individuals with PLWS with and without the chromosome 15 deletion.

Fig. 2

Facial phenotypes of a male with the deletion (top) and a male lacking the deletion (bottom) both with PLWS each shown from ages 1–10 years.

Fig. 3

A prometaphase chromosome 15 idiogram (850 band level) showing the breakpoints at q11 and q13 and representative prometaphase chromosomes of a normal control individual and patients with the interstitial deletion. The 15q12 band is indicated by the arrow in each of the normal chromosomes.

Fig. 4

Family 53166; 12-year-old white male with 46,XY,del(15)(q11q13) karyotype. Parental chromosomes were normal. The patient’s chromosome 15 (D), which carried the deletion, was identified with GTG and QFQ heteromorphisms. Chromosome D has pale satellite intensity with QFQ-banding and small satellite stalk length and normal short arm with GTG-banding. Chromosome D was identified in the father and recognized as the deletion chromosome in the child.

Fig. 5

Family 52937; 8.7-year-old white male with 46,XY,del(15)(q11q13) karyotype. Parental chromosomes were normal. The patient’s chromosome 15 (D), which carried the deletion, was identified with GTG, AgNOR, and QFQ heteromorphisms. Chromosome D has intense satellite intensity with QFQ-banding, large silver precipitate with AgNOR staining and long satellite stalk length and normal short arm with GTG-banding. Chromosome D was identified in the father and recognized as the deletion chromosome in the child.