A Novel KIDINS220 Pathogenic Variant Associated with the Syndromic Spastic Paraplegia SINO: An Expansion of the Brain Malformation Spectrum and a Literature Review
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Brain Imaging
2.3. Genetic Analysis
2.4 Literature Review
3. Results
3.1. Clinical Report
3.2. Genetic Findings
3.3. Spectrum of Brain Malformation in Prenatal Cases and Postnatal Patients Affected by SINO
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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KIDINS220 (NM_020738.4) Variants | Inheritance | Prenatal US (WG) | Age at Brain MRI | Brain MRI | Age at Last Follow-Up Gender | Neurological/ Postmortem Examination | ID | Growth Parameters | Craniofacial Dysmorphisms | References |
---|---|---|---|---|---|---|---|---|---|---|
c. 208del; p.Asp70Ilefs*18 (exon 4) | AR (homozygous) | Dilated ventricles (3/3), CC agenesis (3/3), cerebellar hypoplasia (2/3), cerebellar vermis agenesis (2/3) ↑NT (1/3), CHD (3/3), hydrops fetalis (2/3),polyhydramnios (2/3), ascites (1/3) Normal for gestational age (1/3); NA (2/3) (12, 22 and 24) | / | NP | / 1M, 2F | Limb contractures (3/3) | / | / | Brachyplagiocephaly (3/3), bossed forehead (3/3), deep set eyes (3/3), micrognathia (3/3) | [12] |
c.1263_1264delAA p.Gln421Hisfs*11 (exon 12) pat c.3718-12A>G (inron 27) mat | AR (compound heterozygous) | Bilateral ventriculomegaly (19 +3) Further ventricle enlargement, bilateral talipes equinovarus (20 +3) Polyhydramnios (31) Large for gestational age (35 + 3) | 21 and 27 WG 8th day | 3rd ventricle dilatation, thin corpus callosum, possible absence of the cavum septum pellucidum Thin corpus callosum, thin brainstem, absence of the cavum septum pellucidum, hypoplasia of the basal ganglia, thalami, and inferior cerebellar vermis | 2.5 y F | Coarse nystagmus SP | Severe DD At last follow-up, minimal head control, unable to sit, reach, or grab for items, vocalizations only | COF>99th p, weight at 90th p at birth COF>98th p, length<3rd p, weight at 60th p at 18 m | Frontal bossing, mild micrognathia | [13] |
c.2137-2145del p.Gln713_Leu715del (exon 17) | AR (homozygous) Parents’ first-degree cousins | Severe ventriculomegaly (3/3) (14 and second-semester) Clenched hands, bent wrists, club feet (3/3) Normal for gestational age (3/3) | Post Mortem (P in 1/3) | Triventricular hydrocephalus, cortical atrophy without gyri (lissencephaly), confirmed at autopsy | / 2M, 1F | Limb contractures (3/3) | / | / | - | [11] |
c.3394_3403del; p.Gln1132Serfs*30 (exon 24) | AR (homozygous) | Hydrocephalus/dilated ventricles (2/3), CC agenesis (1/3) NA growth parameters (13, 1 Fe; 18, 2 Fe) | / | NP | / NA | Limb contractures (3/3) | / | / | Micrognathia (1/3) | [10] |
c.3934G>T; p.Glu1312* (exon 28) | AD | NA | / | NP | 39 y F | Nystagmus, SP | Moderate ID (IQ 39 at WAIS) | Severe obesity (BMI 35.6 kg/m2) | - | [8], mother |
NA | / | NP | 17 y M | Nystagmus, SP | Moderate ID (IQ 42 at WAIS) | Obesity (BMI 29.4 kg/m2) | Brachycephaly | [8], elder son | ||
Normal findings | 19 m | Normal findings | 5 y M | SP | Moderate ID | Early-onset overgrowth (macrocephaly, height and weight >99th p), obesity | Brachycephaly | [8], younger son | ||
c.4050G>A; p.Trp1350* (exon 29) | de novo | Dilated lateral ventricles (23) | 12 m | Dilated 3rd and lateral ventricles, ↓ WM bulk, mild delay in myelination, mild generalized atrophy | 14 y M | Nystagmus, axial hypotonia, SP | Moderate ID; he speaks in sentences since 4 y | Early-onset overgrowth (OFC, height and weight >90th p) | Brachyplagiocephaly, bossed forehead, deep-set eyes | [6], patient 1 |
c.4096C>T; p.Gln1366* (exon 30) | de novo | Dilated lateral ventricles (20) | 24 m | Dilated 3rd and lateral ventricles, ↓ WM bulk, mild generalized atrophy | 15 y M | Nystagmus, squint, SP | Moderate ID; he speaks in sentences since 4 y | Early-onset overgrowth (OFC, height and weight >90th p) | Brachyplagiocephaly, prominent forehead, deep-set eyes, crowded teeth | [6], patient 2 |
c.4144G>T; p.Glu1382* (exon 30) | de novo | Unilateral ventriculomegaly (3rd trimester) | 22 m | Lateral ventricle enlargement, pellucidum septum agenesis, CC hypoplasia, verrticalized hippocampi, thin and dysmorphic brainstem | 18 y M | Monolateral squint, SP | Severe ID; he speaks in sentences | Early-onset macrocephaly, obesity | High forehead | Present study |
17 y | Also, dysmorphic and hypoplastic ALIC, partial fusion of lenticular and caudate nuclei, corticospinal tract thinning, optic chiasm hypoplasia, ↓ frontal and temporal lobe volume with cortical gyration simplification, absence of superior cerebellar peduncles decussation | |||||||||
c.4389_c.4390delAG; p.Ser1463Serfs*15 (exon 30) | de novo | Normal findings | 3 y | Periventricular WM high signals at FLAIR, ↓ splenium and posterior corpus callosi, chiasma opticum, and optic nerve hypoplasia | 3 y F | SP | Mild ID | Obesity | Short philtrum, ectropion of nostril, plump cheeks | [7] |
c.4448C>G; p.Ser1483* (exon 30) | AD | NA | / | NP (5/5) | NA 3M, 2F | SP (5/5) | - (5/5) | Normal (5/5) | - (5/5) | [9] |
c.4520dup; p.Leu1507Phefs*4 (exon 30) | de novo | Dilated lateral ventricles | 30m | High-riding 3rd ventricle, dilated lateral ventricles, partial CC agenesis | 7 y M | Nystagmus, squint, SP | Moderate ID; few single words by 24 m | Early-onset obesity | Brachyplagiocephaly, prominent forehead | [6], patient 3; The variant has been also reported in a patient with NDD [18,19] |
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Bonati, M.T.; Baldoli, C.; Taurino, J.; Marchetti, D.; Larizza, L.; Finelli, P.; Iascone, M. A Novel KIDINS220 Pathogenic Variant Associated with the Syndromic Spastic Paraplegia SINO: An Expansion of the Brain Malformation Spectrum and a Literature Review. Genes 2024, 15, 1190. https://doi.org/10.3390/genes15091190
Bonati MT, Baldoli C, Taurino J, Marchetti D, Larizza L, Finelli P, Iascone M. A Novel KIDINS220 Pathogenic Variant Associated with the Syndromic Spastic Paraplegia SINO: An Expansion of the Brain Malformation Spectrum and a Literature Review. Genes. 2024; 15(9):1190. https://doi.org/10.3390/genes15091190
Chicago/Turabian StyleBonati, Maria Teresa, Cristina Baldoli, Jacopo Taurino, Daniela Marchetti, Lidia Larizza, Palma Finelli, and Maria Iascone. 2024. "A Novel KIDINS220 Pathogenic Variant Associated with the Syndromic Spastic Paraplegia SINO: An Expansion of the Brain Malformation Spectrum and a Literature Review" Genes 15, no. 9: 1190. https://doi.org/10.3390/genes15091190