Mutation (AA) | Age | Age of death | PVNH | Other neurological findings | Aortic dilatation | Other cardiac involvement | Skeletal findings | Skin findings | Gastro-intestinal involvement | Other | Reference | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | p.Ala39Glu | 37y | ND | Yes | Transient neonatal convulsions Mega cisterna magna | No | MVP with mild MR TAV with mild AR | No | No | ND | Bilateral epicanthic folds Telecanthus Anteverted nared Anteverted helices | [11] |
2 | p.Leu80Val | 5y | ND | Yes | ND | No | MVP with MR TVP with TR | Bilateral hip dislocation Joint hypermobility Brachydactyly Genu recurvatum | Skin laxity Excess skin folds over the fingers | ND | Low set, posteriorly rotated ears Telecanthus Epicanthal folds Periorbital fullness Infraorbital creases | This report |
3 | p.Met102Val | 3y | ND | Yes | Cerebellar hypoplasia Mildly delayed milestones | No | PDA | ND | ND | ND | Cryptorchidism | [47] |
4 | p.Ile119Asn | ND | 57y | Yes | Mega cisterna magna | Yes (60 mm) | MVP with MR | ND | ND | ND | Thrombopenia | [11] |
5 | p.Lys127Asn | 15y | ND | Yes | Mega cisterna magna | Yes (31 mm) | Mild MVP Thick MV | Joint hypermobility (8/9) Mild pectus carinatumScoliosis | Soft, mildly hyperelastic skin Umbilical hernia | ND | ND | [43] |
6 | p.Ile129Met | 1d | ND | Yes | ND | No | Dysplastic MV and TV | ND | Skin laxity | ND | High arched palate | [43] |
7 | p.Ser149Phe | 38y | ND | Yes | Complex partial and generalized seizures | No | AR | ND | ND | ND | ND | [47] |
8 | p.Arg285Cys | 10y | ND | Yes | Seizures | No | MVP, small ASD | Joint hypermobility (6/9) | Thin,translucent, elastic skin Supraumbilical hernia | ND | High arched palate | [43] |
9 | p.Lys331* (mosaic) | 1d | ND | Yes | Cerebral vasculature dysplasia Corpus callosum hypoplasia | No | PDA, VSD | ND | ND | Intestinal pseudo-obstruction (IPO) Malrotation Short gut syndrome with dilated small intestine | Bifid uvula Persistent Thrombocytopenia | [10] |
10 | p.Gly475* | 17y | ND | Yes | ND | ND | ND | ND | ND | ND | ND | [7] |
11 | c.1692-2A > G (mosaic) | 49y | ND | Yes | Cerebellar hypoplasia Partial complex and generalized seizures | Yes | AV replacement at 26y | Pes cavus | ND | ND | Bifid epiglottis | [47] |
12 | p.Phe611_Gly615del | 18y | 50y | ND* | Spinal osteo-arthritis Muscle hypotonia | No | Severe polyvalvular heart dysplasia Dilatation of both atria Chronic heart failure | Joint hypermobility (8/9) Scoliosis Genua valga, Bilateral varus deformity | Soft and doughy skin Skin laxity Atrophic scar Prominent veins | ND | Dysmorphic facial features | [20] |
13 | p.Gly641Gly | 1d | ND | Yes | ND | No | Septal defect PVP Dysplastic TV | Talipes equinovarus | Inguinal hernia | Severe constipation Malrotation | Hypertelorism Downslanting palpebral fissures Low set, posteriorly rotated ears | [12] |
14 | p.Leu656Phe | ND | ND | Yes | Seizures | ND | ND | ND | ND | ND | ND | [21] |
15 | p.Ala1833_Ser1835delinsAsp | 1d | 2 m | Yes | Corpus callosum hypoplasia Cervical syringomyelia | Yes | Dysplastic aorta, MV and TV ASD, small VSD, PDA Tortuous supra-aortic vessels Pulmonary hypertension with heart failure | Joint hypermobility | Skin laxity | Malrotation (autopsy) | ND | [43] |
16 | p.Gly1896Arg (mosaic) | 57y | ND | Yes | Seizures Mega cisterna magna | No | ND | ND | ND | ND | Progressive obstructive lung disease | [27] |
17a | p.Glu2142AlafsTer22 | 19y | ND | No | No | Yes | Severe MR with MVP Moderate AR Dilatation of the bilateral pulmonary arteries | Pectus excavatum | Bilateral inguinal hernias Thin skin | Intestinal malrotation CIPO Crohn’s disease | Thrombocytopenia | [34] |
17b | 11y | ND | No | No | No | Moderate MR with MVP ASD | No | Bilateral inguinal hernias | Intestinal malrotation CIPO | Cryptorchidism | ||
18 | p.Ala2257Pro | 16y | ND | Yes | Moderate weakness and atropy of the intrinsic hand muscles and wrist extensors bilaterally Seizures | No | PDA AV dysfunction | Joint hypermobility (7/9) Pectus excavatum Bilateral genu recurvatum | Skin laxity | Malrotation Short gut syndrome | ND | [42] |
19a | p.Tyr2305* | ND | ND | Yes | Seizures | ND | ND | ND | ND | ND | ND | |
19b | 36y | 36y | Yes | Seizures | Yes | AR Left ventricular hypertrophy Left atrial enlargement | ND | ND | ND | ND | ||
20 | p.Gln2341* | Prenatally | 6w | Yes | Posterior fossa arachnoid cyst | ND | ND | Spina bifida occulta Proximally placed thumbs | ND | Diaphragmatic defect Displaced stomach and spleen Short gut syndrome with dilated loops of small intestine | “Square face”, flat philtrum Wide metopic suture High-arched palate | [18] |
21 | p.Ser2352* (mosaic) | 38y | ND | Yes | Inward rotation of anterior ventricular horns Corpus callosum hypoplasia Mega cisterna magna | ND | ND | Broad and flattened OPD I-like end phalanges of both feet | ND | ND | Retrognathia Hypertelorism Low-set ears | [27] |
22 | p.Pro2554Leu | 56y | ND | Yes | ND | ND | ND | ND | ND | ND | ND | [7] |
23 | p.Gly2593Glu | ND | ND | Yes | Seizures Migraines | No | ND | Joint hypermobility Tall thin habitus | ND | ND | Left-sided sensorineural hearing loss Retinal lattice degeneration High arched palate | [44] |
24a | p.Asp2622_Lys2623del | 5y | ND | Yes | Corpus callosum hypoplasia Mega cisterna magna | ND | ND | Scoliosis Mild platyspondyly Spatulate finger tips Short, broad phalanges and metacarpus Skeletal dysplasia of the posterior fossa and frontal sinuses Delayed bone age | ND | ND | Dysmorphic facial features | |
24b | Neonatal | ND | Yes | Corpus callosum hypoplasia Mega cisterna Magna | ND | ND | Mild platyspondyly, Spatulate finger tips Short broad phalanges and metacarpus Skeletal dysplasia of the posterior fossa and frontal sinuses Delayed bone age | ND | Malrotation | Dysmorphic facial features | ||
25 | p.Pro2641Ala p.Tyr2642ThrfsTer63 | 1d | 2y | ND* | Broad interhemispheric fissures and subarchnoid spaces with echogenic parenchyma Muscle hypoplasia and hypotonia | No | Dysmorphic/elongated cusps TV with TVR Thinned/elongated cusps MV with MVP, ASD Dilated pulmonary arteries Pulmonary hypertension, leading to heart failure and early demise | Joint hypermobility Pectus excavatum | Translucent skin | Chronic diarrhea | Dysmorphic facial features Food allergies Recurrent bronchitis | This report |
26a | p.Pro2641Leu | 1d | ND | Yes | Enlarged anterior fontanel Ventriculomegaly Seizures Mental retardation | No | PDA | ND | ND | ND | Severe bronchodysplasia | [41] |
26b | 1d | 8 m | Yes | Enlarged anterior fontanel Ventriculomegaly Microgyria Microcephaly | No | PDA | ND | ND | ND | Severe bronchodysplasia resulting in death | ||
27a | p.*2648Serext*101 | Neonatal | ND | Yes | Corpus callosum hypoplasia Retrocerebellar cyst | No | PDA | ND | Inguinal hernia | Pyloric stenosis Constipation Malrotation Short gut syndrome | Dysmorphic facial features | |
27b | Neonatal | ND | Yes | Mildly delayed motor development – hyptonia Retrocerebellar cyst | No | Mildly dysplastic MV PDA | Mild pectus excavatum | ND | Severe constipation Gastro-intestinal obstruction Short gut syndrome | Recurrent upper respiratory tract infections Dysmorphic facial features | ||
27c | 1d | ND | Yes | Hypoplastic cerebellum and vermis | No | ASD | ND | ND | Short gut syndrome Malrotation | Dysmorphic facial features |