This is the report of two independent families in which a balanced maternal translocation led to trisomy 12 p in one of each their offspring. Evaluation of 21 further case reports indicates that this is a phenotypically well defined syndrome which leads to severe developmental retardation. It can be recognized by a characteristic combination of craniofacial anomalies which are summarized in a phantom picture. The gene sequences which produce the typical features in the trisomic state must be localized distally to band 12p12, which is the breakpoint in the partial trisomies. The specific craniofacial anomalies are not visibly modified by the length of the trisomic segment or additional small monosomies or trisomies of recipient chromosomes. However, the frequency and severity of organ malformations and the resulting probability of survival seem to decrease with increasing degrees of chromosomal imbalance. A cytogenetic classification of the 21 inherited translocations and a segregation analysis from the pedigree data was performed. For the different types of translocations the calculated risk figures are given.

Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22),add(12)(p13)/46,idem,t(3;8)(p21;q13 ),add(10) (q26),der(15)del(15)del(15)(q15q22)ins(15;?) q15;?)/46,id em,-X,+2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations.

Partial trisomy 8qter→q23 or q24.1 has been reported in 15 literature cases. We add two further case reports here. Patient 1 inherited the derivative (2) of a balanced maternal reciprocal translocation t(2;8)(qter;q2300) after 2:2 disjunction and adjacent‐1 segregation, and is trisomic for the segment 8qter→q2300. Patient 2 inherited a recombinant (8) of a balanced maternal inverted insertion inv ins(8)(q1300;q2300q24.2) and is trisomic for the segment 8q24.2→q2300. The phenotype of both patients is described and compared to the spectrum of symptoms established from the 15 literature cases. This spectrum contains all features observed with a frequency of > = 50%. Patient 1 had 35% of the features of this spectrum; Patient 2 had 47%. The intrauterine survival probability of unbalanced offspring is assumed to be the same in both cases, as nearly the same segments are trisomic. The pedigrees indicate that the inversion carrier may have a reduced production probability of unbalanced gametes and therefore a reduced risk compared to the translocation carrier.

Short reports A pericentric inversion duplication of the subcentromeric region of chromosome 12q The proband, a 1 year old girl, was referred because of dysmorphic features and developmental delay. There was no family history of congenital abnormalities and the mother had received no drugs during her pregnancy. The mother was 25 and the father 26 years old at the time of the birth. The pregnancy was normal and the birth uncomplicated. She learnt to sit at 3 months and to crawl at 5 months. She now walks unaided, yet she does not talk or make any sounds. She appears to understand what is said to her. The only abnormalities are a large protruding tongue and epicanthic folds. Cultured peripheral lymphocytes were used for chromosomal analysis with GTG and R banding. All 15 cells examined showed an elongation of the short arm of one of the chromosomes 12. This was evaluated in the G banded slides as an inverted duplication in the short arm of the immediate subcentromeric region of the long arm: dup(12p)(qll-ql2) (figure). The chromosomes of both parents were normal.