ORPHA:453499
Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome
Synonyms: Au-Kline syndrome · HNRNPK-related neurodevelopmental disorder · Okamoto syndrome
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal dominant, Not applicable
- Age of onset
- Antenatal, Infancy, Neonatal
- Status
- active
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, hypotonia, craniofacial dysmorphism (such as ridged metopic sutures, long palpebral fissures, broad nasal bridge, hypoplastic alae nasi, low-set, prominent ears, prominent midline tongue groove, and downturned mouth), congenital heart defects, and variable skeletal abnormalities including hip dysplasia, vertebral anomalies, and scoliosis. Additional reported manifestations include high pain tolerance and genitourinary anomalies. Brain imaging may show a thin corpus callosum or white matter abnormalities.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome | Au-Kline syndrome · HNRNPK-related neurodevelopmental disorder · Okamoto syndrome |
| fr | Syndrome de dysmorphie craniofaciale-anomalies squelettiques-cardiopathie-trouble neurologique du développement | Syndrome d'Au-Kline · Syndrome d'Okamoto |
| de | Neurologische Entwicklungsstörungen-kranio-faziale Dysmorphie-Herzfehler-Skelettanomalie-Syndrom | Au-Kline-Syndrom · HNRNPK-bedingte neurologische Entwicklungsstörung · Okamoto-Syndrom |
| es | Síndrome de trastorno del neurodesarrollo-dismorfia craneofacial-defecto cardíaco-anomalías esqueléticas | Síndrome de Au-Kline · Trastorno del neurodesarrollo asociado a HNRNPK |
| it | Malattia del neurosviluppo-dismorfismi craniofacciali-cardiopatie-anomalie scheletriche | Malattia del neurosviluppo correlata a HNRNPK · Sindrome di Au-Kline · Sindrome di Okamoto |
| nl | Neurologische ontwikkelingsstoornis - craniofaciale dysmorfie - hartdefect - skeletanomalieën-syndroom | HNRNPK-gerelateerde neurologische ontwikkelingsstoornis · Syndroom van Au-Kline · Syndroom van Okamoto |
| pt | Síndrome de doença do neurodesenvolvimento-dismorfia craniofacial-anomalia cardíaca-anomalias esqueléticas | Doença do neurodesenvolvimento HNRNPK-relacionada · Síndrome Au-Kline · Síndrome Okamoto |
| pl | Zespół zaburzeń neurorozwojowych-dysmorfii twarzoczaszki-wady serca-anomalii szkieletowych | Zespół zaburzeń neurorozwojowych, dysmorfii czaszkowo-twarzowej, z towarzyszącymi wadami serca i kości |
| cs | Syndrom zahrnující neurovývojovou poruchu, kraniofaciální dysmorfismus, srdeční vady a kyčelní dysplázii | = en |
| uk | Синдром порушення нейророзвитку-черепно-лицьового дизморфізму-серцевої вади-скелетних аномалій | Синдром Ау-Клайна · Повязане з HNRNPK порушення нейророзвитку · Синдром Окамото |
| zh | 神经发育障碍-颅面畸形-心脏缺损-骨骼异常综合征 | 金氏综合征 |
| tr | Nörogelişimsel bozukluk-kraniyofasiyal dismorfizm-kalp defekti-iskelet anomalileri sendromu | Au-Kline sendromu |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 616580 | BTNT | validated | |
| ICD-10 | Q87.8 | NTBT | attributed | validated |
| ICD-11 | LD2F.1Y | NTBT | attributed | validated |
| MONDO | 18681 | E | validated | |
| UMLS | C4225274 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (4):
- ORPHA:93454Dysostosis with predominant vertebral and costal involvement
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases - ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases - ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases - ORPHA:156532Rare syndrome with cardiac malformations
rare developmental anomalies during embryogenesis; rare cardiac malformations; rare genetic diseases
Codes that Orphanet moved or referred to this one:
- ORPHA:2729Okamoto syndrome moved to · inactive
4
Genes
0 direct · 2 via subtypesOrphanet records no gene directly on this code.
Recorded by Orphanet on subtypes of this disorder:
| Gene | Subtype | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|---|
| HNRNPK | ORPHA:453504Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to a point mutation | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:5044 | ENSG00000165119 | 600712 | 9q21.32 | heterogeneous nuclear ribonucleoprotein K | 26173930[PMID] |
| HNRNPK | ORPHA:352665Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to 9q21.3 microdeletion | Role in the phenotype of | Assessed | HGNC:5044 | ENSG00000165119 | 600712 | 9q21.32 | heterogeneous nuclear ribonucleoprotein K | 26173930[PMID]_24501764[PMID]_25348648[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 25 cases | Worldwide | Case(s) | Validated | 29904177[PMID]_30998304[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_30998304[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
71 annotations · validated 2019-12-10| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0001627 | Abnormal heart morphology | |
| HP:0011039 | Abnormal helix morphology | |
| HP:0000119 | Abnormality of the genitourinary system | |
| HP:0000280 | Coarse facial features | |
| HP:0000750 | Delayed speech and language development | |
| HP:0000126 | Hydronephrosis | |
| HP:0001252 | Hypotonia | |
| HP:0001249 | Intellectual disability | |
| HP:0000276 | Long face | |
| HP:0000637 | Long palpebral fissure | |
| HP:0001270 | Motor delay | |
| HP:0002465 | Poor speech | |
| HP:0000431 | Wide nasal bridge | |
| Frequent (79-30%) | ||
| HP:0012332 | Abnormal autonomic nervous system physiology | |
| HP:0000175 | Cleft palate | |
| HP:0002019 | Constipation | |
| HP:0001363 | Craniosynostosis | |
| HP:0000028 | Cryptorchidism | |
| HP:0002714 | Downturned corners of mouth | |
| HP:0001508 | Failure to thrive | |
| HP:0000221 | Furrowed tongue | |
| HP:0002020 | Gastroesophageal reflux | |
| HP:0002579 | Gastrointestinal dysmotility | |
| HP:0000365 | Hearing impairment | |
| HP:0000218 | High palate | |
| HP:0001385 | Hip dysplasia | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0010880 | Increased nuchal translucency | |
| HP:0001511 | Intrauterine growth retardation | |
| HP:0003186 | Inverted nipples | |
| HP:0000252 | Microcephaly | |
| HP:0000194 | Open mouth | |
| HP:0005487 | Prominent metopic ridge | |
| HP:0000508 | Ptosis | |
| HP:0001315 | Reduced tendon reflexes | |
| HP:0002650 | Scoliosis | |
| HP:0000586 | Shallow orbits | |
| HP:0001883 | Talipes | |
| HP:0000430 | Underdeveloped nasal alae | |
| HP:0001629 | Ventricular septal defect | |
| HP:0003422 | Vertebral segmentation defect | |
| HP:0000076 | Vesicoureteral reflux | |
| Occasional (29-5%) | ||
| HP:0025487 | Abnormality of bladder morphology | |
| HP:0001284 | Areflexia | |
| HP:0004970 | Ascending tubular aorta aneurysm | |
| HP:0001631 | Atrial septal defect | |
| HP:0006695 | Atrioventricular canal defect | |
| HP:0001647 | Bicuspid aortic valve | |
| HP:0000193 | Bifid uvula | |
| HP:0009794 | Branchial anomaly | |
| HP:0003763 | Bruxism | |
| HP:0000589 | Coloboma | |
| HP:0000476 | Cystic hygroma | |
| HP:0002282 | Gray matter heterotopia | |
| HP:0002046 | Heat intolerance | |
| HP:0000666 | Horizontal nystagmus | |
| HP:0007550 | Hypohidrosis or hyperhidrosis | |
| HP:0000821 | Hypothyroidism | |
| HP:0007328 | Impaired pain sensation | |
| HP:0000158 | Macroglossia | |
| HP:0001324 | Muscle weakness | |
| HP:0011470 | Nasogastric tube feeding in infancy | |
| HP:0000677 | Oligodontia | |
| HP:0000938 | Osteopenia | |
| HP:0001357 | Plagiocephaly | |
| HP:0002202 | Pleural effusion | |
| HP:0004467 | Preauricular pit | |
| HP:0001954 | Recurrent fever | |
| HP:0001250 | Seizure | |
| HP:0003396 | Syringomyelia | |
| Very rare (<4-1%) | ||
| HP:0011024 | Abnormality of the gastrointestinal tract | |
Run the differential on the 12 obligate / very frequent terms
Annotation source: 30998304[PMID]_29904177[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/453499
- This record as JSON: /data/d/453499.json