Milo’s Medical Timeline: Symptoms, Tests, and Surgeries
Below is a quick list of symptoms, keywords and identified mutations for parents and doctors wondering if their child or patient might be dealing with something similar. These are roughly in the order that we discovered them. This list excludes many false diagnoses and negative test results that we experienced (e.g. he was misdiagnosed in the NICU with a syndrome he does not have; he has received numerous tests for various metabolic disorders which he does not have; we have lost track of the number of MRIs/CT scans/X-rays he has had etc.).
Individuals with scientific training may wish to refer directly to research on Milo’s case in the American Journal of Medical Genetics and in Genetics in Medicine.
- Thick nuchal translucency (4.6 mm) reading at 11 weeks into the pregnancy
- CVS results (11 weeks into the pregnancy): normal karyotype. Micro-array also came back negative.
- Low amniotic fluid in the third trimester, but all prenatal stress tests were fine.
- Two pre-natal echocardiograms and additional ultrasounds indicated no problems.
- Transverse lie at birth. Delivery at term in the 40th week of pregnancy via planned c-section.
- Normal APGAR scores upon birth, uncomplicated c-section (one oddity: very thick vernix).
- Low blood sugar and jaundice discovered over 12 hours after birth. These resolved once we figured out how to feed him, and with UV exposure.
- Abdominal and cranial ultrasounds, chest x-ray, hand x-ray in NICU identified no abnormalities.
- Results from hearing and vision tests in NICU were normal. However, we observed nystagmus and sunsetting of the eyes which self-resolved months later without intervention.
- Heart PFO: not hemodynamically significant
- Cleft palate (small, soft palate only) => successful corrective surgery in December 2011
- Myringotomy (ear) tubes inserted during cleft repair
- Significant hypotonia
- Enlarged fontanelle, slow to close
- Abnormal MRIs: interpretation at birth raised several potential concerns, but at 3 years old, the only remaining item of note is reduced white matter
- Global developmental delay
- Bilateral ptosis => successful corrective surgery (silicone frontalis sling) in February 2012.
- Apparent lacrimal duct obstruction (which caused eye gunk to accumulate). Lacrimal ducts were successfully probed and cleared during the ptosis surgery.
- C1 stenosis (asymptomatic) => successful corrective surgery in February 2013
- Mild sleep apnea, enlarged tonsils => successful tonsillectomy & adenoidectomy in December 2013
- Tethered spinal cord (asymptomatic) => successful corrective surgery in December 2013
- No seizures so far. EEG at age 2 ½ indicated no abnormalities
- Small copy number gain at chromosome Xq12 [arr Xq12(65,083,017-65,823,985)x2 mat] inherited from his mother. Currently believed to be inconsequential.
From exome sequencing (conducted by GeneDx):
- de novo mutation in KDM1A/LSD1, missense substitution in the KDM1A/LSD1 gene, c.2353T>C, predicting p.Tyr785His. KDM1A/LSD1 mutations were not identified in medical literature prior to Milo, whereas there are now three medical journal articles about him and his KDM1A/LSD1 mutation. Mutations in KDM6A have been associated with Kabuki syndrome.
- de novo mutation in ANKRD11, three-nucleotide deletion: c.2606_2608delAGA, p.Lys869del. Mutations on ANKRD11 have been associated with KBG syndrome, but Milo does not present consistently with KBG syndrome and his specific ANKRD11 mutation is not similar to those with KBG syndrome. Currently, there are fewer than 10 documented cases worldwide of children with different mutations on ANKRD11. The implications of these mutations are not well understood. ANKRD11 is located on 16q24.3. 16q24.3 deletions have also been associated with developmental delays, though reported cases characterized as 16q24.3 microdeletion syndrome have typically involved deletions of hundreds of thousands of base pairs affecting more than one gene.
(These are technical terms for unusual physical features he has that we or our geneticists find notable, although they are not harmful)
- slightly elevated anterior hairline
- frontal bossing
- minor downslanting of the palpebral fissures
- slightly blue sclera as a baby
- slight hypertelorism
- anteverted nares
- small, low-set ears
- triangular mouth with downturned corners
- brachydactyly (short fingers and toes)
- hypoplastic toenails
- small hands and feet
- single palmar crease on left hand
- unusual order of baby teeth emergence
- sacral dimple