Pure 9p Trisomy Derived from a Terminal Balanced Unreciprocal Translocation

Summary: Pure 9p trisomy derived from a terminal balanced unreciprocal translocation: The 9p trisomy is a relatively frequent disorder, while pure 9p trisomies are less frequent and usually derived from 9;22 translocations, duplications or 9p extra chromosomes. Here we report a patient with pure trisomy 9p derived from a terminal balanced unreciprocal translocation. The patient derived to the genetic service by psychomotor delay, presented at 2 years and 11 months: short stature, open anterior fontanelle, dysplastic ears, facial dysmorphisms, long and broad first toes with hypoplastic nails, central nervous system and skeletal alterations. The patient karyotype was: 46,XY,der(l0)t(9;10) (pl3.l;qter)mat while the mother karyotype was: 46,XX,t(9; 10)(p 13.1 ;qter). The presence of the subtelomeric region of lOq showed by FISH as well as the duplication of 9p subtelomere was further confirmed with multiplex ligation dependent probe amplification (MLPA) for the subtelomeric region of all chromosomes. The mechanism of formation seems to be due to a telomere break in lOq leading to loss of telomeric functions, permitting the 9p fusion; this has been supported with molecular probes showing telomere shortening in interstitial telomeric repeats, which are unable to prevent chromosome fusion. This is one of the few cases reported with terminal translocations (not jumping) preserving the subtelomeric region and highlights the importance of subtelomeric probes in terminal arrangements, and the utility of molecular probes, such as MLPA in defining this kind of abnormalities. In the clinical context, the patient presented a high proportion of 9p trisomy features which is expected considering the large 9p segment involved and the presence of the critical region 9p22.Key-words: Trisomy 9p-Terminal translocation.INTRODUCTIONTrisomy 9p or Rethore syndrome was first described by Rethore et al. in 1970 (15) and further delineated by Centerwall in 1975 (4); it represents the fourth autosomic trisomy in frequency, after the 21,13 and 18 (12,17). With more than 200 cases reported so far, its clinical phenotype can be described within a wide variability, according to the length of the 9p arm involved. The main characteristics of the syndrome include: microcephaly, mental retardation, short stature, facial anomalies, scoliosis and less frequently cardiopathy, renal and central nervous system malformations (21).Pure 9p trisomies represent a small proportion of all 9p trisomy cases as most of them arise from a parental (usually maternal) balanced translocation, producing 9p trisomies and other chromosome's monosomies. Pure 9p trisomies are usually the product of derivatives of 9;22 translocations (1,8,20), 9p duplications (10,23) or a 9p extra chromosome (9). Here, we report a patient with a pure 9p trisomy derived from a terminal translocation in his mother and discuss the possible mechanism of formation.CASE REPORTThe propositus, a 2 year 11 months-old boy, was the third child of an apparently healthy 37 year-old mother, and 50 year-old father. He has three brothers, the youngest of which has not yet presented any problem; the two older brothers (aged 12 and 4 years old) presented speech problems (tachylalia and dysphemia, respectively), with normal motor and cognitive development. There were no other similarly affected relatives. The pregnancy was normal with an adequate prenatal control. The patient was bom at 39 weeks of gestation, with a birth weight of 3550 g and a birth height of 53 cm, and he presented spontaneous breathing and crying with an APGAR score of 7-9. At birth a dislocation of his left hip was detected. At the age of 6 months, his mother noticed that the child did not grow according to his age and presented psychomotor delay. He sat at 15 months and walked at 2 years 11 months, however, he does not yet speak. In addition, hyperactivity and an autoaggressive behavior were present.PHYSICAL EXAMINATIONAt the present age (2 years 11 months), the patient weighs 11 kg (Pc 3-10) he has a height of 77 cm (Pc -3) and a cephalic circumference of 47 cm (Pc 3-10). …