PYCR2-related microcephaly-progressive leukoencephalopathy
- Type
- Malformation syndrome
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy
- Status
- active
PYCR2-related microcephaly-progressive leukoencephalopathy is a rare, genetic, syndromic intellectual disability disorder characterized by progressive postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial hypotonia, appendicular hypertonia with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and failure to thrive. Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | PYCR2-related microcephaly-progressive leukoencephalopathy | |
| fr | Microcéphalie avec leucoencéphalopathie progressive associée à PYCR2 | |
| de | PYCR2-abhängige Mikrozephalie-progressive Leukoenzephalopathie | |
| es | Microcefalia asociada a PYCR2-leucoencefalopatía progresiva | |
| it | Microcefalia con leucoencefalopatia progressiva correlata a PYCR2 | |
| nl | PYCR2-gerelateerde microcefalie - progressieve leuko-encefalopathie | |
| pt | Microcefalia-leucoencefalopatia progressiva PYCR2-relacionada | |
| pl | Małogłowie - postępująca leukoencefalopatia zależne od PYCR2 | |
| cs | PYCR2-vázaná mikrocefalie s progresivní leukoencefalopatií | |
| uk | PYCR2-асоційована мікроцефалія-прогресуюча лейкоенцефалопатія | |
| zh | PYCR2相关小头畸形-进行性脑白质发育不良 | |
| tr | PYCR2 -ilişkili mikrosefali ilerleyici lökoensefalopati |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 616420 | E | validated | |
| ICD-10 | Q87.8 | NTBT | attributed | validated |
| MONDO | 0018825 | E | validated | |
| MONDO | 14632 | E | validated | |
| MONDO | 18825 | E | validated | |
| UMLS | C4225332 | 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 (3):
- 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:269528Syndrome with microcephaly as a major feature
rare developmental anomalies during embryogenesis; rare genetic diseases; rare neurological diseases
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| PYCR2 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:30262 | ENSG00000143811 | 616406 | 1q42.12 | pyrroline-5-carboxylate reductase 2 | 25865492[PMID]_27130255[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 18 cases | Worldwide | Case(s) | Validated | 25865492[PMID]_27130255[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_25865492[PMID]_27130255[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
62 annotations · validated 2020-01-08| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0001344 | Absent speech | |
| HP:0001508 | Failure to thrive | |
| HP:0011968 | Feeding difficulties | |
| HP:0002540 | Inability to walk | |
| HP:0001249 | Intellectual disability | |
| HP:0000253 | Progressive microcephaly | |
| HP:0011344 | Severe global developmental delay | |
| Frequent (79-30%) | ||
| HP:0001999 | Abnormal facial shape | |
| HP:0000414 | Bulbous nose | |
| HP:0003429 | CNS hypomyelination | |
| HP:0002376 | Developmental regression | |
| HP:0030890 | Hyperintensity of cerebral white matter on MRI | |
| HP:0002079 | Hypoplasia of the corpus callosum | |
| HP:0000327 | Hypoplasia of the maxilla | |
| HP:0001252 | Hypotonia | |
| HP:0000369 | Low-set ears | |
| HP:0000411 | Protruding ear | |
| HP:0001250 | Seizure | |
| HP:0007258 | Severe demyelination of the white matter | |
| HP:0003202 | Skeletal muscle atrophy | |
| HP:0001257 | Spasticity | |
| HP:0002013 | Vomiting | |
| Occasional (29-5%) | ||
| HP:0000924 | Abnormality of the skeletal system | |
| HP:0001274 | Agenesis of corpus callosum | |
| HP:0000718 | Aggressive behavior | |
| HP:0000463 | Anteverted nares | |
| HP:0001166 | Arachnodactyly | |
| HP:0001251 | Ataxia | |
| HP:0002069 | Bilateral tonic-clonic seizure | |
| HP:0011229 | Broad eyebrow | |
| HP:0010055 | Broad hallux | |
| HP:0011304 | Broad thumb | |
| HP:0100704 | Cerebral visual impairment | |
| HP:0000494 | Downslanted palpebral fissures | |
| HP:0000565 | Esotropia | |
| HP:0001371 | Flexion contracture | |
| HP:0011166 | Focal myoclonic seizure | |
| HP:0001288 | Gait disturbance | |
| HP:0002283 | Global brain atrophy | |
| HP:0000365 | Hearing impairment | |
| HP:0000218 | High palate | |
| HP:0002827 | Hip dislocation | |
| HP:0005072 | Hyperextensibility at wrists | |
| HP:0001347 | Hyperreflexia | |
| HP:0000316 | Hypertelorism | |
| HP:0002365 | Hypoplasia of the brainstem | |
| HP:0006460 | Increased laxity of ankles | |
| HP:0000737 | Irritability | |
| HP:0001382 | Joint hypermobility | |
| HP:0002509 | Limb hypertonia | |
| HP:0000343 | Long philtrum | |
| HP:0000400 | Macrotia | |
| HP:0000341 | Narrow forehead | |
| HP:0000639 | Nystagmus | |
| HP:0000396 | Overfolded helix | |
| HP:0000768 | Pectus carinatum | |
| HP:0002465 | Poor speech | |
| HP:0000319 | Smooth philtrum | |
| HP:0000233 | Thin vermilion border | |
| HP:0005659 | Thoracic kyphoscoliosis | |
| HP:0000325 | Triangular face | |
| HP:0000582 | Upslanted palpebral fissure | |
Run the differential on the 7 obligate / very frequent terms
Annotation source: 27860360[PMID]_27130255[PMID]_25865492[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/481152
- This record as JSON: /data/d/481152.json