ORPHA:508533
Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome
Synonyms: EXTL3-related neuro-immuno-skeletal dysplasia syndrome · Neuro-immuno-skeletal dysplasia syndrome due to EXTL3 deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Antenatal, Neonatal
- Status
- active
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by the association of developmental delay, variable intellectual disability, skeletal dysplasia, and in many cases T-cell immunodeficiency and other immunologic abnormalities. Skeletal findings include short stature, anomalies of the long bones, hands and feet, and pelvis, platyspondyly, cervical malformation, and pectus excavatum. Dysmorphic facial features, such as coarse face, hypertelorism, and broad nasal tip, may be present. Additional reported manifestations are seizures, hyperreflexia, nystagmus, and muscular hypotonia, as well as multiple liver cysts.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome | EXTL3-related neuro-immuno-skeletal dysplasia syndrome · Neuro-immuno-skeletal dysplasia syndrome due to EXTL3 deficiency |
| fr | Syndrome de dysplasie squelettique-déficit immunitaire à cellules T-retard de développement | Syndrome neuro-immunologique associée à EXTL3 · Syndrome neuro-immunologique-dysplasie squelettique par déficit en EXTL3 |
| de | Skelettdysplasie-T-Zell-Immundefekt-Entwicklungsverzögerung-Syndrom | EXTL3-assoziiertes neuro-immuno-skelettales Dysplasie-Syndrom · Neuroimmune Skelettdysplasie durch EXTL3-Defekt |
| es | Síndrome de displasia esquelética-inmunodeficiencia de células T-retraso del desarrollo | Síndrome de displasia neuro-inmuno-esquelética asociada a EXTL3 · Síndrome de displasia neuro-inmuno-esquelética por deficiencia de EXTL3 |
| it | Sindrome displasia scheletrica-immunodeficienza delle cellule T-ritardo dello sviluppo | Sindrome displasia neuro-immuno-scheletrica correlata a EXTL3 · Sindrome displasia neuro-immuno-scheletrica correlata a deficit di EXTL3 |
| nl | Skeletdysplasie - T-cel-immuundeficiëntie - ontwikkelingsachterstand-syndroom | EXTL3-gerelateerde neuro-immuno-skeletale dysplasiesyndroom · Neuro-immuno-skeletale dysplasiesyndroom door EXTL3-deficiëntie |
| pt | Síndrome de displasia esquelética-imunodeficiência células T-atraso do desenvolvimento | |
| pl | Zespół dysplazji szkieletowej-niedoboru odporności związanej z limfocytami T-opóźnionego rozwoju | Zespół dysplazji neuro-immuno-szkieletowej związanej z EXTL3 · Zespół dysplazji neuro-immuno-szkieletowej wywołanej niedoborem EXTL3 |
| cs | Syndrom zahrnující skeletální dysplázii, imunodeficienci T buněk a opoždění vývoje | Syndrom EXTL3-vázané neuroimunoskeletální dysplázie · Syndrom neuroimunoskeletální dysplázie způsobené deficitem EXTL3 |
| uk | Синдром скелетної дисплазії-Т-клітинного імунодефіциту-затримки розвитку | Синдром нейро-імуно-скелетної дисплазії, повязаний з EXTL3 · Синдром нейро-імуно-скелетної дисплазії внаслідок дефіциту EXTL3 |
| zh | 骨骼发育不良-T细胞免疫缺陷-发育迟缓综合症 | EXTL3相关的神经-免疫-骨骼发育不良综合征 |
| tr | İskelet displazisi-T hücre immün yetmezlik-gelişme geriliği sendromu | EXTL3 eksikliğine bağlı nöro-immüno-iskelet displazi sendromu · EXTL3-ilişkili nöro-immüno-iskelet displazi sendromu |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 617425 | E | validated | |
| ICD-10 | Q87.8 | NTBT | attributed | validated |
| ICD-11 | 4A01.32 | NTBT | attributed | validated |
| MONDO | 0033682 | E | validated | |
| UMLS | C5567899 | 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:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases - ORPHA:169349Immuno-osseous dysplasia
rare genetic diseases; rare immunological diseases - ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases - ORPHA:93434Spondylodysplastic dysplasia
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases
No children.
4
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| EXTL3 | Disease-causing germline mutation(s) in | Assessed | HGNC:3518 | ENSG00000012232 | 605744 | 8p21.1 | exostosin like glycosyltransferase 3 | 28132690[PMID]_28148688[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 12 cases | Worldwide | Case(s) | Validated | 28132690[PMID]_28148688[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_28132690[PMID]_28148688[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
95 annotations · validated 2020-01-23| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0000924 | Abnormality of the skeletal system | |
| HP:0001263 | Global developmental delay | |
| HP:0001270 | Motor delay | |
| HP:0004565 | Severe platyspondyly | |
| Frequent (79-30%) | ||
| HP:0001999 | Abnormal facial shape | |
| HP:0000765 | Abnormal thorax morphology | |
| HP:0002813 | Abnormality of limb bone morphology | |
| HP:0003319 | Abnormality of the cervical spine | |
| HP:0002867 | Abnormality of the ilium | |
| HP:0008807 | Acetabular dysplasia | |
| HP:0045060 | Aplasia/hypoplasia involving bones of the extremities | |
| HP:0001156 | Brachydactyly | |
| HP:0001230 | Broad metacarpals | |
| HP:0009768 | Broad phalanges of the hand | |
| HP:0004313 | Decreased circulating antibody level | |
| HP:0031381 | Decreased lymphocyte proliferation in response to mitogen | |
| HP:0005403 | Decreased total T cell count | |
| HP:0025336 | Delayed ability to sit | |
| HP:0003498 | Disproportionate short stature | |
| HP:0002007 | Frontal bossing | |
| HP:0032061 | Hypereosinophilia | |
| HP:0003311 | Hypoplasia of the odontoid process | |
| HP:0001265 | Hyporeflexia | |
| HP:0001252 | Hypotonia | |
| HP:0001249 | Intellectual disability | |
| HP:0002808 | Kyphosis | |
| HP:0001888 | Lymphopenia | |
| HP:0000252 | Microcephaly | |
| HP:0003375 | Narrow greater sciatic notch | |
| HP:0010049 | Short metacarpal | |
| HP:0003196 | Short nose | |
| HP:0009803 | Short phalanx of finger | |
| HP:0001328 | Specific learning disability | |
| Occasional (29-5%) | ||
| HP:0000733 | Abnormal repetitive mannerisms | |
| HP:0001344 | Absent speech | |
| HP:0000463 | Anteverted nares | |
| HP:0008936 | Axial hypotonia | |
| HP:0100865 | Broad ischia | |
| HP:0000414 | Bulbous nose | |
| HP:0005306 | Capillary hemangioma | |
| HP:0002341 | Cervical cord compression | |
| HP:0008462 | Cervical instability | |
| HP:0008445 | Cervical spinal canal stenosis | |
| HP:0002676 | Cloverleaf skull | |
| HP:0000280 | Coarse facial features | |
| HP:0001363 | Craniosynostosis | |
| HP:0004315 | Decreased circulating IgG level | |
| HP:0002850 | Decreased circulating total IgM | |
| HP:0032218 | Decreased proportion of CD4-positive T cells | |
| HP:0005415 | Decreased proportion of CD8-positive T cells | |
| HP:0000490 | Deeply set eye | |
| HP:0002750 | Delayed skeletal maturation | |
| HP:0005280 | Depressed nasal bridge | |
| HP:0009053 | Distal lower limb muscle weakness | |
| HP:0002307 | Drooling | |
| HP:0002987 | Elbow flexion contracture | |
| HP:0003051 | Enlarged metaphyses | |
| HP:0011166 | Focal myoclonic seizure | |
| HP:0000293 | Full cheeks | |
| HP:0001290 | Generalized hypotonia | |
| HP:0002197 | Generalized-onset seizure | |
| HP:0000212 | Gingival overgrowth | |
| HP:0002240 | Hepatomegaly | |
| HP:0000085 | Horseshoe kidney | |
| HP:0001347 | Hyperreflexia | |
| HP:0001276 | Hypertonia | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0002540 | Inability to walk | |
| HP:0003212 | Increased circulating IgE concentration | |
| HP:0030320 | Increased intervertebral space | |
| HP:0004894 | Laryngotracheal stenosis | |
| HP:0009826 | Limb undergrowth | |
| HP:0002996 | Limited elbow movement | |
| HP:0000276 | Long face | |
| HP:0003189 | Long nose | |
| HP:0000343 | Long philtrum | |
| HP:0002938 | Lumbar hyperlordosis | |
| HP:0000347 | Micrognathia | |
| HP:0001634 | Mitral valve prolapse | |
| HP:0000160 | Narrow mouth | |
| HP:0008763 | No social interaction | |
| HP:0000639 | Nystagmus | |
| HP:0000194 | Open mouth | |
| HP:0002179 | Opisthotonus | |
| HP:0001561 | Polyhydramnios | |
| HP:0001830 | Postaxial foot polydactyly | |
| HP:0001177 | Preaxial hand polydactyly | |
| HP:0000520 | Proptosis | |
| HP:0006532 | Recurrent pneumonia | |
| HP:0000960 | Sacral dimple | |
| HP:0001250 | Seizure | |
| HP:0004430 | Severe combined immunodeficiency | |
| HP:0011344 | Severe global developmental delay | |
| HP:0005619 | Thoracolumbar kyphosis | |
| HP:0002119 | Ventriculomegaly | |
Run the differential on the 4 obligate / very frequent terms
Annotation source: 28148688[PMID]_28331220[PMID]_28132690[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/508533
- This record as JSON: /data/d/508533.json