GENETIC REPORT FROM DR. LEBEL - Troy seen 7/18/13 at 3 months of age

Here is a copy of the results from the genetics doctor.  I'm afraid it offers more unanswered questions than we had previously....

Differential diagnosis for an individual w/ developmental delays and/or malformation(s) must include1) normal familial variation 2) sporadic events 3) environmental or teratogenic events. 4) chromosomal (aneuploid) states 5) heriditary (mendelian) traits and 6) combination of these.When multiple abnormalities are present, it is difficult to accept either a sporadic event or a teratogenic influence. Rather, it is more likely that a genetic cause (either mendelian or chromosomal) is involved. 

This patient is remarkable for septo-optic dysplasia and adrenal insufficiency, with a few dysmorphic features (low set ears, small penis, undescended testicle, anteverted nares and epicanthus inversus),making him discontinuous.  The family history is unenlightening. We have no evidence of potentially teratogenic events.  It is obvious that we are not seeing one of the more common major aneuploid states but small deletions and duplications may present w/ diverse (uncluding apparently minor) features. In this case any inheritance pattern is possible (except for direct inheritance from an affected parent).

The London Dysmorphology Database (Winter and Baraitser, 2013) is useful in searching for candidate syndromes.  Searching the database for syndromes characterized by low set ears, anteverted nares, bulbous nasal tip, diastasis recti, redundant nuchal  skin, small penis, undescended tessticle, adrenal insufficency and dysplasia of the optic nerves, we find over 1400 syndromes with at least one of the features of interest. We find no syndromes with all 9 of the search criteria, nor do we find any with 8, 7 or 6 of the search characteristics.  There are numerous syndromes with 5 of the search criteria, none of which are attractive candidate syndromes due to lack of pathognomonic features of these syndrome in this patient.  Of these, the only syndromes that actually included the most salient features (septo-optic dysplasia), was CHARGE syndrome, which appears to be a poor choice for this patient.  Some of the other were involved with copy number variants, and this might be worth pursuing if developmental patterns do not prove to be normal.

We should make note that the child's mother was only 16 at the time of birth, and that isolated sporadic septo-optic dysplasia is associated with early maternity.  Thus it could be an isolated nonsyndromic event, but close follow-up is indicated because there are some other suggestive signs of dysmorphism and we would not want to miss the opportunity to detect early any signs of disordered developmental patterns.  It is, however, recognition of her current favorable pattern and the possibility of a nonsyndromic event that leads me to offer no genetic test at present. 

Since we do not have a final diagnosis, we cannot know the actual recurrence risk. It might be less than 1% (associated with a sporadic event), but is also could be as high as the 25% that is associated with autosomal recessive inheritance.  Consequently, we should assume the latter until or unless we can disprove it as our hypothesis.