TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare multiple congenital anomalies/dysmorphic syndrome characterized by profound intellectual disability with absent speech, severe infantile hypotonia with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset epilepsy, strabismus and post-natal onset of progressive brain atrophy (including loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (including plagio/brachycephaly, bitemporal narrowing, high-arched eyebrows high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome | |
| fr | Syndrome d'encéphalopathie-hypotonie sévère-dysmorphie craniofaciale associé à TBCK | |
| de | TBCK-assoziierte Enzephalopathie-schwere Hypotonie-kraniofaziale Dysmorphie-Syndrom | TBCK-Syndrom |
| es | Síndrome de encefalopatía-hipotonía grave-dismorfia craneofacial asociado a TBCK | |
| it | Disabilità intellettiva correlata a TBCK | |
| nl | TBCK-gerelateerde encefalopathie - ernstige hypotonie - craniofaciale dysmorfie-syndroom | |
| pt | Síndrome de encefalopatia-hipotonia grave-dismorfia craniofacial TBCK-relacionada | |
| pl | Zespół niepełnosprawności intelektualnej związany z TBCK | |
| cs | Syndrom TBCK-vázané mentální retardace | |
| uk | Синдром інтелектуальної недостатності, повязаний з TBCK | |
| zh | TBCK相关智力障碍综合征 | |
| tr | TBCK -ilişkili zihinsel yetersizlik sendromu |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 616900 | E | validated | |
| ICD-10 | Q87.0 | NTBT | attributed | validated |
| ICD-11 | LD90.Y | NTBT | attributed | not yet validated |
| MONDO | 0014823 | E | validated | |
| UMLS | C5567480 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (2):
- 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
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| TBCK | Disease-causing germline mutation(s) in | Assessed | HGNC:28261 | ENSG00000145348 | 616899 | 4q24 | TBC1 domain containing kinase | 27040691[PMID]_27040692[PMID]_27275012[PMID]_27748029[PMID]_18541960[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 25 cases | Worldwide | Case(s) | Validated | 27748029[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_27748029[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.
HPO phenotypes
73 annotations · validated 2020-01-13| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0003444 | EMG: chronic denervation signs | |
| HP:0001319 | Neonatal hypotonia | |
| HP:0003323 | Progressive muscle weakness | |
| HP:0006829 | Severe muscular hypotonia | |
| Frequent (79-30%) | ||
| HP:0003119 | Abnormal circulating lipid concentration | |
| HP:0001999 | Abnormal facial shape | |
| HP:0002518 | Abnormal periventricular white matter morphology | |
| HP:0001284 | Areflexia | |
| HP:0000280 | Coarse facial features | |
| HP:0000750 | Delayed speech and language development | |
| HP:0002283 | Global brain atrophy | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0002540 | Inability to walk | |
| HP:0031165 | Multifocal seizures | |
| HP:0001315 | Reduced tendon reflexes | |
| HP:0002093 | Respiratory insufficiency | |
| HP:0001250 | Seizure | |
| HP:0011344 | Severe global developmental delay | |
| HP:0003202 | Skeletal muscle atrophy | |
| HP:0002119 | Ventriculomegaly | |
| Occasional (29-5%) | ||
| HP:0000337 | Broad forehead | |
| HP:0000414 | Bulbous nose | |
| HP:0100543 | Cognitive impairment | |
| HP:0002750 | Delayed skeletal maturation | |
| HP:0002376 | Developmental regression | |
| HP:0011198 | EEG with generalized epileptiform discharges | |
| HP:0100288 | EMG: myokymic discharges | |
| HP:0000286 | Epicanthus | |
| HP:0002705 | High, narrow palate | |
| HP:0001007 | Hirsutism | |
| HP:0002045 | Hypothermia | |
| HP:0000821 | Hypothyroidism | |
| HP:0009826 | Limb undergrowth | |
| HP:0000256 | Macrocephaly | |
| HP:0000158 | Macroglossia | |
| HP:0000939 | Osteoporosis | |
| HP:0000767 | Pectus excavatum | |
| HP:0002650 | Scoliosis | |
| HP:0000340 | Sloping forehead | |
| HP:0010804 | Tented upper lip vermilion | |
| HP:0000574 | Thick eyebrow | |
| HP:0001629 | Ventricular septal defect | |
| Very rare (<4-1%) | ||
| HP:0000878 | 11 pairs of ribs | |
| HP:0004691 | 2-3 toe syndactyly | |
| HP:0012547 | Abnormal involuntary eye movements | |
| HP:0002099 | Asthma | |
| HP:0000717 | Autism | |
| HP:0007302 | Bipolar affective disorder | |
| HP:0001500 | Broad finger | |
| HP:0001837 | Broad toe | |
| HP:0011734 | Central adrenal insufficiency | |
| HP:0030084 | Clinodactyly | |
| HP:0007957 | Corneal opacity | |
| HP:0000028 | Cryptorchidism | |
| HP:0000824 | Decreased response to growth hormone stimulation test | |
| HP:0000490 | Deeply set eye | |
| HP:0001540 | Diastasis recti | |
| HP:0000964 | Eczematoid dermatitis | |
| HP:0000836 | Hyperthyroidism | |
| HP:0000343 | Long philtrum | |
| HP:0000303 | Mandibular prognathia | |
| HP:0000252 | Microcephaly | |
| HP:0000011 | Neurogenic bladder | |
| HP:0000639 | Nystagmus | |
| HP:0001562 | Oligohydramnios | |
| HP:0005487 | Prominent metopic ridge | |
| HP:0001642 | Pulmonic stenosis | |
| HP:0000407 | Sensorineural hearing impairment | |
| HP:0000470 | Short neck | |
| HP:0000486 | Strabismus | |
| HP:0000664 | Synophrys | |
| HP:0000582 | Upslanted palpebral fissure | |
| HP:0000431 | Wide nasal bridge | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 29283439[PMID]_27748029[PMID]_25558065[PMID]_27040691[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/488632
- This record as JSON: /data/d/488632.json