Table 1.

Four probands identified with heteroyzgous variants in POU4F1.

	Proband 1	Proband 2	Proband 3	Proband 4
Variant	de novo, heterozygous	de novo, heterozygous	de novo, heterozygous	de novo, heterozygous
	c.917A>G; p.Gln306Arg	c.158_161dup;p.Leu55AlafsTer295	c.283_290del; p.Thr95SerfsTer251	c.271_281del;p.Thr91HisfsTer254
Sex	Female	Male	Male	Female
Current Age	3 yrs 5 months	3 yrs, 10 months	4 yrs, 2 months	22 years old
Birth History	Born at 39 weeks via C-section	Born at 38 weeks via vaginal delivery	Born at 41 weeks by induced vaginal delivery	Born at 39 weeks gestation via vaginal delivery
	Birth wt: 8lbs 1 oz	Birth wt: 7 lbs 7 oz	Birth wt: 8 lb 10 oz	Birth wt: 8 lbs 0.8 oz
	Had initial oxygen requirements, but went to the floor with mother	Uneventful birth history	Uneventful birth history	Uneventful birth history
Respiratory system	Concern for aspiration with thin liquids at age 2 years	No issues	No issues	No issues
Cardiovascular system	No issues	No issues	No issues	No issues
Gastrointestinal systetm	Had early swallowing difficulties; correction of ankyloglossia	No issues	Chronic constipation, better since bowel cleanout	No issues
Renal system	No issues	No issues	No issues	No issues
Musculoskeletal system	Scoliosis (dextroconvex curvature from T5 to L3); prominent thoracic kyphosis with borderline upper limits of normal lumbar lordosis	No known issues	No known issues	Scoliosis and Scheuermann’s disease
Hematologic system	Excessive bleeding after ankyloglossia surgery; dx with von Willebrand’s disease	No issues	No issues	No issues
Ophthalmologic system
strabismus	Left eye esotropia s/p strabismus surgery	None appreciated	Left eye esotropia s/p surgery at 14 months and 39 months	Bilateral esotropia s/p surgery
nystagmus	None appreciated	None appreciated	None appreciated	Slow vertical torsional nystagmus noted on slit-lamp examination
other abnormal movements	None appreciated	None appreciated	None appreciated	Spontaneous drifts of the eyes upwards superimposed on tonically held upgaze (after resolution of paroxysmal tonic upgaze)
ophthalmoplegia	None appreciated	None appreciated	None appreciated	None appreciated
other	Paroxysmal tonic upgaze; wears glasses	Paroxysmal tonic upgaze		Paroxysmal tonic upgaze, later convergence insufficiency
Audiology	Normal hearing	Normal hearing	Normal hearing	Normal hearing
Neurological system
Intention tremor	Present	Present	Present (particularly with right upper extremity)	Present
Ataxia	Present (falls frequently, poor balance and coordination)	Present (falls frequently, poor balance and coordination)	Present	Present
Hypotonia	Present	Present	Present (low truncal tone most pronounced)	Present (from infancy; central and peripheral; currently cannot lift anything >10 lbs)
Developmental delay/intellectual disability	Global developmental delay	Global developmental delay	Global developmental delay	Isolated motor delays from infancy; learning disability/mild cognitive delays noted at older age
Seizures	None	None	None	None
Developmental Regression	None	None	None	None
Trigeminal involvement	Possible difficulty clenching mouth	None appreciated	Denies difficulty chewing	None
Deep tendon reflexe	Patellar 2+ reflexes	Patellar 1+ reflexes	Decreased DTRs (1+ for biceps, tricpes, brachioradialis, and patella bilaterally; 2+ for Achilles)	Biceps 0/4 bilaterally; Triceps and brachioradialis 1/4 bilaterally; Patellar 2/4 bilaterally, Achilles 2+ bilaterally
Other			Nerve conduction studies normal at 9 months	Dysmetria, dysarthria, speech apraxia. EEG normal at age 2 years.
Developmental Milestones	Rolled over at 8 months in both directions; sat at 10 months; crawled at 14 months; walked at age 2 years.	Walked at 3 years 1 month.	Rolled over at 9 months in both directions; sat at 9 months; crawled at 2.5 years; at 4 years is able to walk with a gait trainer	Rolled over in both directions at 18 months; sat at 3 years; walked independently at 8–10 years; received Special Education throughout school.
Growth Parameters
Height	64th% at age 2 years	24th% at 3 years 6 months	15th% at 2 years 4 months; 16th% at 4 years 4 months	5th% at 3 years 6 months
Weight	62nd% at age 2 years	48th% at 3 years 6 months	25th% at 2 years 4 months; 28th% at 4 years 4 months	5th% at 3 years 6 months
HC	45th% at age 2 years	20th% at 3 years 6 months	33rd% at 2 years 4 months; 17th% at 4 years 4 months	10th% at 3 years 6 months