Objectives MEDLINE (1970-Dec 2012, EMBASE (1980-Dec 2012 and CINAHL (1982-June 2012

We report the identification of six patients with 3q29 microdeletion syndrome. The clinical phenotype is variable despite an almost identical deletion size. The phenotype includes mild-to-moderate mental retardation, with only slightly dysmorphic facial features that are similar in most patients: a long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest-wall deformity, and long and tapering fingers were noted in at least two of six patients. Additional features--including microcephaly, cleft lip and palate, horseshoe kidney and hypospadias, ligamentous laxity, recurrent middle ear infections, and abnormal pigmentation--were observed, but each feature was only found once, in a single patient. The microdeletion is approximately 1.5 Mb in length, with molecular boundaries mapping within the same or adjacent bacterial artificial chromosome (BAC) clones at either end of the deletion in all patients. The deletion encompasses 22 genes, including PAK2 and DLG1, which are autosomal homologues of two known X-linked mental retardation genes, PAK3 and DLG3. The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome.

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There was no excess of stillbirths, low birthweight or congenital malformations, and no cancers have occurred in the 49 offspring after treatment. There was a significant excess of twins, compared with national expectations, in offspring of female patients (RR=8.52, P=0.025). Aggregation of series from the literature also showed an excess of twins. Chromosomes from cultures of peripheral lymphocytes from 45 children born to 25 patients (11 men and 14 women) after treatment were examined for numerical abnormalities and for structural abnormalities at the 550 or greater band level of resolution. All were normal except in one child with Down's syndrome (47, XY,+21), for whom we found the origin of the trisomy was from the parent without Hodgkin's disease. The chromosome constitution was also abnormal in one miscarriage (69, XXY; originating from the parent without Hodgkin's disease) and one termination (45, X; for which the parental origin could not be determined) after treatment. The study adds to previous questionnaire data and for the first time provides data also from chromosome analysis, that offspring of patients treated in adulthood for Hodgkin's disease are not at greatly raised risk of genotoxic or other adverse outcomes as a consequence of their parent's treatment. The numbers of offspring assessed in the literature remains small, however, and surveillance of larger numbers of subjects is needed to enable reliable treatment-specific analyses.

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