Table 1 LZTR1-related Patients with Noonan syndrome and GH deficiency in the literature
Literature | Age | Sex | Hereditary form | Variant location | Nucleotide change | Amino acid change | Origin of variant | Phenotype | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
(years) | Facial and physical features | Short stature | Cardiac defect | Others | |||||||
Johnston, J. J, et al. [8] | 3.2 | F | AR | Within intron 16 of LZTR1 affecting BTB 2 | c.1943–256C > T | *70G > A | MC, FC | Prenatal polyhydramnios; proptosis; ptosis; wide mouth; low-set ears; bulbous nasal tip; relative macro- cephaly | + | HCM; small ASD | Delayed development; decreased muscle mass and motor coordination |
Nakaguma, M. A, et al. [19] | 12.5 | M | AR | Kelch 5 | c.881G > T | p.R294L | MC | Ptosis; triangular face; high-arched palate; low-set ears; micrognathia; pectus excavatum | + | Transposition of the great vessels; PVS; inter- ventricular and interatrial communication | NA |
BTB 2 | c.2212C > T | p.Q738* | FC | ||||||||
Pagnamenta, A. T, et al. [7] | 5 | M | AD | Kelch 2 | c.407A > G | p.Y136C | De novo | Congenital ptosis; depressed nasal bridge; low-set, posteriorly rotated ears; pointed chin; wide intermamillary distance; barrel-shaped chest; pectus excavatum; 2–3 toe syndactyly; cryptorchidism | + | Mild PVS | Delayed speech and language development; generalized hypotonia; delayed development |
Our study | 6.6 | F | AD | Kelch 6 and BTB might be lost | c.1149 + 1G > A | Disrupts splice site (donor) | MC | Hypertelorism; downslanting palpebral fissures; epicanthal folds; squinting; nystagmus; low-set, oval-shaped, posteriorly rotated ears with a thick helix; short broad nose with a depressed root and full tip; deeply grooved and long philtrum; high and wide peaks of the vermilion; highly arched palate; micrognathia; short neck; cubitus valgus; scoliosis; pectus excavatum; café au lait spots; mild hypertrichosis | + | – | Delayed psychomotor development; hemivertebra deformity; refractive errors |