X-linked intellectual deficit, Najm type

General Information (adopted from Orphanet):

Synonyms, Signs: MRXSNA
MENTAL RETARDATION, X-LINKED, SYNDROMIC, NAJM TYPE
MICPCH SYNDROME
MICPCH
X-linked intellectual deficit - microcephaly - pontocerebellar hypoplasia
Number of Symptoms 64
OrphanetNr: 163937
OMIM Id: 300749
ICD-10: Q04.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 35 families [Orphanet]
Inheritance: X-linked
X-linked dominant
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic syndrome with a cerebellar malformation as major feature
 -Rare genetic disease
Syndrome with a cerebellar malformation as major feature
 -Rare developmental defect during embryogenesis
 -Rare neurologic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
2
 (HPO:0001090) Large eyes 20 / 7739
3
 (HPO:0000518) Cataract Frequent [Orphanet] 454 / 7739
4
 (HPO:0000609) Optic nerve hypoplasia occasional [HPO:skoehler] 26 / 7739
5
 (HPO:0000543) Optic disc pallor occasional [HPO:skoehler] 67 / 7739
6
 (HPO:0000479) Abnormality of the retina Occasional [Orphanet] 74 / 7739
7
 (HPO:0000639) Nystagmus Frequent [Orphanet] rare [HPO:skoehler] 555 / 7739
8
 (HPO:0000486) Strabismus Frequent [Orphanet] occasional [HPO:skoehler] 576 / 7739
9
 (HPO:0000545) Myopia Frequent [Orphanet] 286 / 7739
10
 (HPO:0000505) Visual impairment Frequent [Orphanet] 297 / 7739
11
 (HPO:0004322) Short stature 1232 / 7739
12
 (HPO:0004325) Decreased body weight Occasional [Orphanet] 492 / 7739
13
 (HPO:0002198) Dilated fourth ventricle 12 / 7739
14
 (HPO:0001252) Muscular hypotonia 990 / 7739
15
 (HPO:0001290) Generalized hypotonia 51 / 7739
16
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
17
 (HPO:0010547) Muscle flaccidity 466 / 7739
18
 (HPO:0008936) Muscular hypotonia of the trunk 77 / 7739
19
 (HPO:0001324) Muscle weakness 859 / 7739
20
 (HPO:0001347) Hyperreflexia 363 / 7739
21
 (HPO:0001276) Hypertonia Occasional [Orphanet] 317 / 7739
22
 (HPO:0001257) Spasticity 251 / 7739
23
 (HPO:0001263) Global developmental delay 853 / 7739
24
 (HPO:0002342) Intellectual disability, moderate 37 / 7739
25
 (HPO:0001344) Absent speech 57 / 7739
26
 (HPO:0002167) Neurological speech impairment Occasional [Orphanet] 308 / 7739
27
 (HPO:0001288) Gait disturbance Frequent [Orphanet] 318 / 7739
28
 (HPO:0001250) Seizures Frequent [Orphanet] rare [HPO:skoehler] 1245 / 7739
29
 (HPO:0001327) Photomyoclonic seizures 125 / 7739
30
 (HPO:0000277) Abnormality of the mandible Frequent [Orphanet] 394 / 7739
31
 (HPO:0000347) Micrognathia 426 / 7739
32
 (HPO:0000337) Broad forehead Frequent [Orphanet] 116 / 7739
33
 (HPO:0000252) Microcephaly Frequent [Orphanet] 832 / 7739
34
 (HPO:0000253) Progressive microcephaly 37 / 7739
35
 (HPO:0002650) Scoliosis Occasional [Orphanet] occasional [HPO:skoehler] 705 / 7739
36
 (HPO:0000966) Hypohidrosis 41 / 7739
37
 (HPO:0000300) Oval face 5 / 7739
38
 (HPO:0000218) High palate 356 / 7739
39
 (HPO:0000343) Long philtrum Frequent [Orphanet] 262 / 7739
40
 (HPO:0000455) Broad nasal tip 67 / 7739
41
 (HPO:0000426) Prominent nasal bridge 121 / 7739
42
 (HPO:0003196) Short nose 264 / 7739
43
 (HPO:0000431) Wide nasal bridge 290 / 7739
44
 (HPO:0000445) Wide nose Frequent [Orphanet] 190 / 7739
45
 (HPO:0000286) Epicanthus 371 / 7739
46
 (HPO:0000407) Sensorineural hearing impairment Frequent [Orphanet] rare [HPO:skoehler] 524 / 7739
47
 (HPO:0008527) Congenital sensorineural hearing impairment 165 / 7739
48
 (HPO:0008625) Severe sensorineural hearing impairment 150 / 7739
49
 (HPO:0000400) Macrotia 108 / 7739
50
 (HPO:0008897) Postnatal growth retardation 113 / 7739
51
 (HPO:0002334) Abnormality of the cerebellar vermis Very frequent [Orphanet] 137 / 7739
52
 (HPO:0012795) Abnormality of the optic disc Occasional [Orphanet] 187 / 7739
53
 (HPO:0001321) Cerebellar hypoplasia 114 / 7739
54
 (HPO:0002120) Cerebral cortical atrophy Frequent [Orphanet] 187 / 7739
55
 (HPO:0400004) Long ear Frequent [Orphanet] 94 / 7739
56
 (HPO:0007227) Macrogyria occasional [HPO:skoehler] 9 / 7739
57
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
58
 (OMIM) Brain MRI shows proportionate pontocerebellar hypoplasia 1 / 7739
59
 (OMIM) Hypertelorism, mild 11 / 7739
60
 (OMIM) Lack of speech development 20 / 7739
61
 (OMIM) Mental retardation, moderate to severe 20 / 7739
62
 (OMIM) Most never acquire independent ambulation 1 / 7739
63
 (OMIM) Peripheral hypertonia 4 / 7739
64
 (OMIM) Simplified gyration in the frontal cortex (less common) 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) is an X-linked disorder affecting females and characterized by severe intellectual disability, microcephaly, and variable degrees of pontocerebellar hypoplasia. Affected individuals have very poor psychomotor development, often without ...
Clinical Description OMIM Najm et al. (2008) reported several patients with a phenotype of congenital and marked postnatal microcephaly, severe mental retardation, and disproportionate pontine and cerebellar hypoplasia. Four were female and 1 was male. The first girl was referred at ...
Molecular genetics OMIM Najm et al. (2008) considered CASK an excellent candidate gene for the microcephaly-disproportionate pontine and cerebellar hypoplasia (MICPCH) phenotype since it functions during neuronal development and Cask mutant mice have small brains, abnormal cranial shape, and cleft palate. ...