Cryptic chromosomal deletions detected by array-CGH in four cases affected by central precocious puberty and neurodevelopmental disorders

Background: Central precocious puberty (CPP) may be associated with CNS abnormalities including neurodevelopmental disorders (ND), epilepsy (E), CNS structural malformations and/or with dysmorphic features. In the literature, some chromosomal aberrations have been reported in patients with this association. Objective and hypotheses: The aim of this study was to detect cryptic chromosomal anomalies in patients affected by CPP and CNS disorders using the array CGH technique. Methods: We carried on the array-CGH analysis in 4 girls affected by CPP associated with one or more of following CNS anomalies: ND, E and structural abnormalities detected with MRI. The age at the onset of CPP ranged from 4 to 7.3 years. Results: Case 1. A de novo distal deletion of the chromosome 9 short arm [del(9)(p24.3-p23)] was found, as in the cases affected by 9p- syndrome. To our knowledge, this is the second reported case of precocious puberty associated to 9p distal deletion. Cases 2 and 3. A deletion of the chromosome 8 short arm was found: in the first case the deletion was localized in the region 8p23.2 and in the latter in the region 8p23.3.1. In both these cases the deletion determines the lost of the gene CSMD1, which is known to be particularly expressed in the ovary during the embryogenesis. Moreover, a duplication of CSMD1 has been found in a girl affected by delayed puberty [1]. Case 4. A deletion of chromosome 8p22 was detected, which is cited in the Database of Genomic Variants as a normal variant. However, this deletion may be related with the age at menarche in normal population. Conclusions: Our observations confirm the usefulness of the array-CGH analysis for detecting cryptic chromosomal aberrations in patients with CPP associated with CNS abnormalities and or dysmorphic features. Further studies are needed to identify genes responsible for this association