Table 2. Characteristics of confirmed Brazilian LS patients.
| Patient | Consanguinity | Site of mutation | Type of mutation | c.DNA mutation | Amino Acid Change | Main reported Features | Ref. |
|---|---|---|---|---|---|---|---|
| 1 | +; Family I | GHR | Splice | Intron 6: c.619-1 G>C | At 13 years old: 87.5cm (-8.5 SDS) and 12.4kg. Several hypoglycemic episodes. Late closure of fontanelles. Trunkal obesity, high-pitched voice, doll-like face, irregular hypoplastic teeth and small external genitalia. Absence of pubertal development. | Saldanha and Toledo, 1981 | |
| 2 | +; Family I | GHR | Splice | Intron 6: c.619-1 G>C | At 8 years old: 76cm (-9.4 SDS) and 10kg. Several hypoglycemic episodes. Late closure of fontanelles. Trunkal obesity, high-pitched voice, doll-like face, irregular hypoplastic teeth, small external genitalia and learning difficulties. | Saldanha and Toledo, 1981 | |
| 3 | +; Family II | GHR | Missense | Exon 7: c.731 G>T | p.S244I | At 15.7 years old: 124cm (-6.1 SDS), 43.4 kg and BA=13.2 years. Weight at birth (full term) = 2 kg (< 3rd centile). GH=12mcg/L, IGF1 <18mcg/L, IGFBP3= 1.1mg/L. | Jorge, et al., 2004 |
| 4 | ?; Adopted; Family III | GHR | Nonsense | Exon 5: c.338 dupA | p.Y113X | At 12 years old: 87.8cm (SDS) and 11.1kg. Length at birth = 44cm, and Weight= 3kg. Facial asymmetry, prominent forehead, depressed nasal bridge, short face, blue sclerae and microstomia. Severe dental crowding and high-pitched voice. Small penis (10th percentile). GH=26 mcg/L, IGF-1=22.5 ng/mL. | Diniz et al., 2008 |
| 5 | ?; Family IV * | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | At 17.8 years old: 104.3cm (?7.8 SDS); GH =30mcg/L, GH peak =94mcg/L, IGF1 =23mcg/L, IGFBP3= 0.6mg/L. | Jorge et al., 2005 |
| 6 | +; Family V * | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | At 8.8 years old: 103.3cm (?5.0 SDS); GH 7.2mcg/L, GH peak 118mcg/L, IGF1 <18mcg/L. | Jorge et al., 2005 |
| 7 | ?; Family VI * | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | At 11.3 years old: 113.8cm (-4.5 SDS); GH= 3.3mcg/L, GH peak= 36mcg/L, IGF1 <18mcg/L, IGFBP3= 0.6mg/L. | Jorge et al., 2005 |
| 8 | ?; Family VI * | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | At 6.8 years old: 81cm (-7.6 SDS); IGF1 <18 mcg/L, IGFBP3= 0.4mg/L. | Jorge et al., 2005 |
| 9 | ?; Family VII * | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | At 19.1 years old: 132cm (-6.4 SDS); GH 1.6mcg/L, GH peak= 38mcg/L, IGF1= 51mcg/L. | Jorge et al., 2005 |
| 10 | ?; Family VII * | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | At 3.2 years old: 69cm (-7.4 SDS); GH peak =39mcg/L, IGF1 <18mcg/L. | Jorge, et al., 2005 |
| 11 | ?; Family VIII | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | No data | Gonçalves et al., 2014 |
| 12 | ?; Family VIII | GHR | Splice | Exon 6: c.594 A>G | p.V199_M206del | No data | Gonçalves et al., 2014 |
| 13 | +; Family IX | GHR | Missense | Exon 5 (GHR): c.409 G>A | p.317N | At 6 years old: 86cm (SDS), 10kg and BA= 3 years. Length at preterm birth (28 weeks) =39cm and Weight= 1.7kg. Mild dysmorphic features, atopic eczema, interstitial lung disease, hyperprolactinemia. GH peak =20.6mcg/L, IGF1=34ng/mL. Treatment with GH whithout clear improvement. | Pugliese-Pires et al., 2010 |
| STAT5B | Frameshift | Exon 5 (STAT5B): c.424_427 del | p.L142fs X161 | ||||
| 14 | +; Family IX | STAT5B | Frameshift | Exon 5: c.424_427 del | p.L142fs X161 | At 2 years old: 76cm (SDS), 7,5kg and BA=6.0 months. Length at preterm birth (33 weeks) = 49cm and Weight= 2.4kg. Prominent forehead, depressed nasal bridge and obesity with centripetal fat distribution. Atopic eczema, thrombocytopenic purpura, interstitial lung disease, hyperprolactinemia. | Pugliese-Pires et al., 2010 |
| GH peak =14.2mcg/L, IGF1 < 25ng/mL. Treatment with GH and IGF-1 whithout clear improvement | |||||||
| 15 | +; Family X | STAT5B | Frameshift | Exon 5: c.424_427 del | p.L142fs X161 | Deceased as a consequence of respiratory failure | Scalco et al., 2017 |
| 16 | +; Family X | STAT5B | Frameshift | Exon 5: c.424_427 del | p.L142fs X161 | Deceased as a consequence of respiratory failure | Scalco et al., 2017 |
| 17 | +; Family XI | GHR | Misstart | Exon 2: c.1A>T | p.M1? | At 4 years old: 80.2cm (??? SDS) and BA=2.0 years. Length at birth = 46cm and Weight= 3.450kg. Prominent forehead, depressed nasal bridge, high-pitched voice and delayed dentition. | Present study |
| GH peak>40.0mcg/L, IGF1=12.3ng/mL. | |||||||
| 18 | +; Family XI | GHR | Misstart | Exon 2: c.1A>T | p.M1? | At 2 years old: 73.2cm (SDS). Length at birth = 46cm and Weight= 3.400kg. Prominent forehead, depressed nasal bridge, high-pitched voice, sparse hair and late closure of fontanelles. GH =11.4mcg/L, IGF1=79ng/mL. | Present study |
BA=bone age
*
Family IV-VII are proceeding from a small city of the state of Pernambuco, and consanguinity cannot be ruled out.