This very enlightening paper from Finland is worth reading by all pediatric subspecialists for its wealth of information.  The authors first relate that uniparental disomy (UPD) associated with growth retardation has been found in at least 9 chromosomes (2,6,7,9,14,16,17,20 & 22) and concluded that UPD thus may provide explanations for some cases of growth retardation of unknown cause.  Inheritance of both parental genomes is essential for normal growth and development.

In their study, these authors focused on UPD of chromosome 7 and particularly on maternal or matUPD7.  The study was prompted as matUPD7 has been reported in approximately 10% of patients with Russell Silver syndrome (RSS) and in a few patients with intrauterine growth retardation (IUGR) without RSS.  Basically 2 groups of patients were studied: (1) 39 patients with unequivocal RSS and, (2) 166 patients with unexplained growth retardation but who did not have RSS.  The latter group was divided into 2 subgroups: (2a) those with IUGR and postnatal growth retardation (PNGR) and, (2b) those with only PNGR.  For final analysis, the RSS patients were separated into 2 subgroups also: (1a) RSS with matUPD7, and (1b) those without mat-7-UPD.

Only 6 of the 205 patients studied had matUPD7and all had RSS.  Thirty-three of the 39 in the RSS group did not have UPD.  Comparison of these two groups revealed that RSS infants (with or without matUPD7) were significantly shorter at birth than infants in group 2a and 2b.  The birth weights and lengths of RSS patients with or without matUPD7 were equally small.  However, birth weights did not differ between groups 1a, 1b, and 2a.  Notable difference of parental age at birth was observed between group 1a and the other 3 groups.  MatUPD7 patients had significantly higher (p<.05) maternal age (38 years) and paternal age (40 years) than those in the other 3 groups.   

Midparental heights were near average for all groups. Maternal obstetrical complications known to possibly restrict fetal growth (e.g. toxemia, high blood pressure, and alcohol or tobacco use) were reported in 5 (15%) of 33 of group 1b, 24 (26%)  of 91 in group 2a, and only in 5 (7%) of the 75 mothers of the PNGR (group 2b).

The authors point out that matUPD7 and growth hormone deficiency (GHD) can occur together as can GHD and other causes of IUGR and PNGR, and emphasize that other metabolic disorders do not exclude matUPD7.  MatUPD7 has been reported in 3 patients with cystic fibrosis, all of which were exceedingly short.  Consequently the authors advise screening for matUPD7 if abnormally short stature occurs conjointly with cystic fibrosis or other recessive disorders mapped to chromosome 7.  However, because matUPD7 is rare among IUGR and PNGR patients, except in RSS, screening will be primarily helpful in this group of RSS patients.

 

Editor’s Comment:  The long-term natural history of matUPD7 is not yet clear.  Fertility and possible transmission of UPD has not been evaluated.  For these reasons, and others such as responsiveness to various therapies, screening in appropriate instances is important.  All RSS patients should be screened and those RSS patients with and without matUPD7 should be further evaluated to determine the molecular biological differences between the two groups.  The authors discuss some possibilities in their manuscript.  The entire manuscript is very enlightening and is recommended both for theoretical considerations and factual data.

Judith G. Hall, OC, MD

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