For many years we have known that children with cerebral palsy (CP) have a high rate of congenital malformations, sometimes apparently quite unrelated to the motor disorder. To quote from a few studies: in 1955 Eastman and DeLeon1 found that 14.6/100 children with CP, but only 3.8/100 of controls had been found to have one or more congenital defect at birth. In 1983 Veelken et al.2 reported an excess of malformations of the central nervous system in their series of term born children with diplegia. Illingworth in 19853 reported that in his series of children with CP, 7.7/100 had other congenital anomalies while the expected prevalence was around 2/100. He also referred to work showing that, in affected children, tooth enamel hypoplasia of prenatal origin is more common than expected, as is growth arrest in costochondral junctions, and dermatoglyphic anomalies.
Some might feel that the earliest studies would not meet the current more rigorous assessments necessary to accept the validity of the findings. It is, therefore, the more convincing that the same conclusions have been reached by Rankin et al.4 This work has taken further the investigation reported by Garne and European collaborators in 2008.5 This simply compared the prevalence of congenital malformations reported in a number of high quality and standardized CP registers with that estimated using local population-based congenital malformation registers. Rankin et al.4 linked cases in three CP registers with those in local congenital malformation registers, thus obtaining more clinical information on the matched children. As in the much earlier literature, the excess of congenital malformations in the cerebral palsies was found particularly in children with spastic types of CP rather than dystonia or athetosis, and in those who were term births.
Many researchers have suggested possible reasons for such associations. One is that the apparently unrelated brain and other anomalies resulted from the same cause, whether environmental insult or genetic constitution, even after excluding known syndromes. Barnes6 in her work on developmental defects of the axial skeleton describes ‘developmental fields’ as ‘the close embryonic interaction of select developing tissues involved in the complex composition of a specific structure or set of closely related structures’. She shows how, for instance, depending on the timing of the embryonic disturbance, errors in the field concerned with development of cranial sutures can lead to a variety of types of skull deformation. These must are likely to have an affect normal brain development as well as leading to facial deformities. She is particularly concerned with skeletal development, but there are developmental fields for other systems, where early embryonic errors could lead to a variety of different congenital anomalies. Later in pregnancy, musculoskeletal deformities may result from abnormal fetal movements secondary to brain anomalies, perhaps leading to talipes or dislocated hips.
It has also long been known that different congenital malformations tend to occur together, even in non-syndromic cases. This was the case in the population-based British National Perinatal Mortality Survey.7 Roberts and Powell,8 using their Welsh malformation register data, also found that many more malformed individuals have multiple defects than would be the case if all combinations were fortuitous. A more recent report from a large study based on EUROCAT data9 suggested that structural brain anomalies may be associated with cleft lips and palates. The authors of this paper quote from another report:10‘... from embryological studies it is known that the brain and the face are intimately related in normal and pathological conditions.’ It is hardly surprising that children with CP, which may sometimes result from brain anomalies arising early in pregnancy, will also be unduly likely to have other anomalies.
New clues to causation might be found in intensive investigations of subgroups of CP with similar patterns of associated malformations or anomalies. While each may be very rare, one should now use the burgeoning and very welcome development of rigorously controlled and standardized international collaboration to identify such groups and use any relevant modern technological tools, and embryological expertise, to investigate further possible causes and their timing.
More generally, it is regrettable that many recent workers in the field seem to be unaware of the rich history of good research into the cerebral palsies, and its implications. A remarkable consistency is perhaps the most striking feature of the large body of findings reported over well over 100 years. Once cases of known postnatal causes are excluded, the prevalence of the group, sex ratio, birthweight distributions, proportions of cases with different topological features, and severity and the association with other anomalies, have remained broadly similar over time and in different places. Maybe a translation and publication of Sigmund Freud’s11 excellent papers on the subject (he was a fine neurologist) would provide a salutary and humbling reminder of how much we have still to learn about this group of very disabling conditions.