CHAPTER LXXX 



Disturbances of neural function in the 

 presence of congenital disorders 1 



SAMUFI P HICKS Departments of Patfiology, New England Deaconess Hospital, and 



Harvard Medical School, Boston, M assachusetts 



CHAPTER CONTENTS 



Anatomic Abnormalities 



Anencephaly 



Hereditary Ataxias 

 Inborn Errors of Metabolism 



Phenylketonuria 



Audiogenic Seizures 

 Neoplastic Development 



Retinoblastoma 

 Experimental Congenital Anomalies 



Heteroploidy in Salamanders 

 Concluding Remarks 



ABNORMALITIES OF THE NERVOUS SYSTEM that result 



from faulty development are legion. They affect every 

 kind of organism that has a nervous system and dis- 

 turb function through the most devious mechanisms. 

 Neurophysiologically speaking they have nothing in 

 common except that they involve a nervous system. 

 They may become manifest throughout the life of the 

 organism, for development is something that goes on 

 until death. 



Two problems arise immediately in any considera- 

 tion of congenital anomalies. One is how to chaw a 

 line between what is abnormal and what is biologic 

 variation. Most of us agree on what are frank abnor- 

 malities but minor deviations are usually classified 

 arbitrarily. A more difficult problem is how to decide 

 when an abnormality is primarily a part of the ab- 

 normal developmental process and when it is a 

 secondary consequence. Anencephaly and phenyl- 

 ketonuria are ordinarily considered to be dcvelop- 



1 This work was supported by Public Health Service Grant 

 B-382, United Cerebral Palsy and Atomic Energy Commission 

 Contracts AT(3o-i)i454 and 901. 



mental abnormalities, one expressed at an anatomic, 

 the other at a biochemical level. However, the 

 bruised brain that results when a chronic alcoholic 

 drives his automobile into a tree may be viewed as a 

 secondary consequence of the man's primary develop- 

 mental disorder of personalitv, whatever its origin. 

 In diabetes meUitus, which is a congenital inborn 

 error of metabolism, retinopathy and neuropathy- 

 are usually thought of as intrinsic parts of the disease. 

 However, would we all agree that cerebral arterio- 

 sclerotic apoplexy- or hypoglycemic brain damage 

 from therapeutic insulin are secondary to the dia- 

 betes, or are they, too, a primary pari ol the diabetic 

 process? This sort of difficulty of distinguishing be- 

 tween primary and secondary processes is even more 

 marked in the analysis of the disturbed neurophysi- 

 ology of certain behavior disorders I _>, 5, 21, 26). 



It is obvious that some practical limit will have to 

 be put on what is to be presented in this essay. Per- 

 haps this can be done by considering several condi- 

 tions involving vertebrates thai mosl of us would 

 agree are developmental in the primary sense, that is 

 closely related to the genetic and epigenetic processes. 

 At the same time by a choice of examples the extra- 

 ordinary diversity of congenital neurologic disorders 

 can be emphasized. 



An understanding of how function is disturbed in 

 these conditions rests on a grasp of how they develop. 

 Therefore a review of certain aspects of neurogenesis 

 and some ways it can go wrong is necessary before we 

 can consider them. The primary determinants of how 

 the organism will develop and be shaped by its 

 environment, normally or abnormally, are the chromo- 

 somes in the egg, and they are present from the begin- 

 ning. In this sense any deviation from normal develop- 



191 1 



