Table 1.

Summary of reported TECPR2 mutations and associated phenotype.

Case	Mutation	Presentation	Neuro/Ophth	Autonomic	Behavior	Sleep	Respiratory
1–5 (Oz-Levi 2012)6	c.3416delT (frameshift, p.Leu1139Argfs*75)	Hypotonia and developmental delay at 2 years old	Developmental delay, motor delay, hypotonia. In 4 of 5 who walked, later developed spastic rigid ataxic gait. Areflexia. Four of 5 with episodes of decreased alertness with exacerbation of hypotonia. One with transient severe encephalopathy.	—	Friendly disposition	—	Recurrent pulmonary infections. Severe CA initially during sleep, later evolving to wake state. Four of 5 required MV (3 with spontaneous remission, 1 with chronic MV at 20 years). PSG with CAs (>90/h) and hypoxia.
	Homozygous
	4 of 5 with genetic testing
	Premature truncation of protein
6 (Heimer 2015)3	p.Leu440/p.Thr1891le	Developmental delay, GERD	Hypotonia, decreased reflexes, global developmental delay, astigmatism, myopia	Decreased pain sensitivity, delayed gastric emptying	Cheerful, hyperactive	Frequent arousals at 9 months	Postoperative ARDS, breath holding, PSG at 4 years with AHI 12 events/h, SpO2 nadir 80%, ETCO2 peak 55 mmHg, pneumonia and shock at 6 years leading to death
7 (Heimer 2015)3	p.Leu440/p.Leu440Arfs*19	Floppy infant, dysphagia, and GERD	Developmental delay, areflexia, abrupt somnolence with EEG encephalopathy, esotropia, ataxic gait	Decreased pain sensitivity, temperature dysregulation, episodes of bradycardia with hypertension, sodium/water dysregulation	Friendly, violent mood changes	Arousals on PSG	Tonsillectomy, recurrent aspiration and pneumonia, chronic lung disease, tracheostomy with mechanical ventilator, “apnea” with elevated CO2 (>100 mmHg).
8 (Heimer 2015)3	p.Leu440/p.Leu1139Arfs*75	Dysphagia and GERD in infancy	Developmental delay, areflexia, axial hypotonia	Decreased pain sensitivity, temperature dysregulation, postural hypotension, sodium/water dysregulation	Apathy alternating with restlessness and hyperactivity	Recurrent awakenings	Aspiration, desaturation, recurrent intubation, CA
9 (Covone 2016)8	p.Leu684Val/p.Thr903Met	Gait instability at 4 years	Normal intelligence, brisk reflexes at knee and upper extremities, areflexia at ankles, muscle atrophy, strabismus, ocular apraxia	—	—	—	Respiratory failure at 13 years of age, tracheostomy and mechanical ventilator
	Compound heterozygous missense mutation
10 (Zhu 2015)7	p.Leu440ArgfsTer19	—	Developmental delay, areflexia, severe hypotonia	—	—	—	“Breathing abnormalities”
	Homozygous
	Frameshift mutation
11 (CASE)	p.D259MfsX44c.774delA	Hypotonia at 6 months	Developmental delay, low axial tone, motor coordination immaturity, strabismus	Photophobia, decreased pain sensitivity, chronic constipation	Friendly, hyperactive	Circadian disturbance with advanced sleep phase	Progressive CA, Biot’s breathing
	p.K343RfsX2c.1028_1032delAAGGA
	Compound heterozygous mutation
	Large truncation of the protein

AHI = apnea-hypopnea index; ARDS = acute respiratory distress syndrome; CA = central apnea; EEG, electroencephalogram; ETCO₂ = end-tidal carbon dioxide; GERD = gastroesophageal reflux disease; MV = mechanical ventilation; PSG = polysomnogram; SpO2 = oxygen saturation; TECPR2, tectonin β-propeller–containing protein 2.