X-linked lissencephaly with abnormal genitalia

General Information (adopted from Orphanet):

Synonyms, Signs: XLISG HYDRANENCEPHALY AND ABNORMAL GENITALIA, INCLUDED
LISSENCEPHALY, X-LINKED, WITH AMBIGUOUS GENITALIA
LISX2
XLAG
X-linked lissencephaly - agenesis of the corpus callosum - genital anomalies
XLAG syndrome
X-linked lissencephaly with ambiguous genitalia
Number of Symptoms 63
OrphanetNr: 452
OMIM Id: 300215
ICD-10: Q04.0
Q04.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: X-linked recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: ARX-related epileptic encephalopathy
 -Rare genetic disease
 -Rare neurologic disease
Genetic syndrome with corpus callosum agenesis /dysgenesis as a major feature
 -Rare genetic disease
Other syndrome with lissencephaly as a major feature
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Syndrome with 46,XY disorder of sex development
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare genetic disease
 -Rare urogenital disease
Syndrome with corpus callosum agenesis /dysgenesis as a 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:0000062) Ambiguous genitalia Very frequent [Orphanet] 74 / 7739
2
 (HPO:0000054) Micropenis Very frequent [Orphanet] 257 / 7739
3
 (HPO:0000035) Abnormality of the testis Very frequent [Orphanet] 296 / 7739
4
 (HPO:0008734) Decreased testicular size 105 / 7739
5
 (HPO:0000348) High forehead 157 / 7739
6
 (HPO:0000343) Long philtrum 262 / 7739
7
 (HPO:0000218) High palate 356 / 7739
8
 (HPO:0000219) Thin upper lip vermilion 112 / 7739
9
 (HPO:0000426) Prominent nasal bridge 121 / 7739
10
 (HPO:0000431) Wide nasal bridge 290 / 7739
11
 (HPO:0000347) Micrognathia 426 / 7739
12
 (HPO:0002007) Frontal bossing Occasional [Orphanet] 366 / 7739
13
 (HPO:0000252) Microcephaly Very frequent [Orphanet] 832 / 7739
14
 (HPO:0011341) Long upper lip 5 / 7739
15
 (HPO:0000260) Wide anterior fontanel 55 / 7739
16
 (HPO:0000277) Abnormality of the mandible Occasional [Orphanet] 394 / 7739
17
 (HPO:0009921) Duane anomaly 9 / 7739
18
 (HPO:0000369) Low-set ears 372 / 7739
19
 (HPO:0011344) Severe global developmental delay 46 / 7739
20
 (HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
21
 (HPO:0001257) Spasticity 251 / 7739
22
 (HPO:0001328) Specific learning disability 114 / 7739
23
 (HPO:0001347) Hyperreflexia 363 / 7739
24
 (HPO:0002251) Aganglionic megacolon Occasional [Orphanet] 78 / 7739
25
 (HPO:0001276) Hypertonia Occasional [Orphanet] 317 / 7739
26
 (HPO:0008872) Feeding difficulties in infancy 153 / 7739
27
 (HPO:0012092) Abnormality of exocrine pancreas physiology Occasional [Orphanet] 9 / 7739
28
 (HPO:0002024) Malabsorption Frequent [Orphanet] 142 / 7739
29
 (HPO:0002028) Chronic diarrhea 51 / 7739
30
 (HPO:0011968) Feeding difficulties 240 / 7739
31
 (HPO:0002014) Diarrhea 225 / 7739
32
 (HPO:0001629) Ventricular septal defect Occasional [Orphanet] 316 / 7739
33
 (HPO:0001643) Patent ductus arteriosus Occasional [Orphanet] 228 / 7739
34
 (HPO:0004370) Abnormality of temperature regulation Frequent [Orphanet] 58 / 7739
35
 (HPO:0001252) Muscular hypotonia Frequent [Orphanet] 990 / 7739
36
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
37
 (HPO:0010547) Muscle flaccidity 466 / 7739
38
 (HPO:0001324) Muscle weakness 859 / 7739
39
 (HPO:0001302) Pachygyria 60 / 7739
40
 (OMIM) No development 1 / 7739
41
 (OMIM) Impaired temperature regulation 1 / 7739
42
 (OMIM) Pinched nasal alae 1 / 7739
43
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum Very frequent [Orphanet] 180 / 7739
44
 (HPO:0002119) Ventriculomegaly Frequent [Orphanet] 253 / 7739
45
 (OMIM) Lissencephaly, posterior to anterior gradient 1 / 7739
46
 (HPO:0002171) Gliosis 48 / 7739
47
 (OMIM) Moderately thickened cortex 1 / 7739
48
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
49
 (HPO:0001339) Lissencephaly 30 / 7739
50
 (OMIM) Dysplastic basal ganglia 1 / 7739
51
 (HPO:0001417) X-linked inheritance 173 / 7739
52
 (OMIM) Learning difficulties in affected females 1 / 7739
53
 (OMIM) Underdeveloped scrotal folds 1 / 7739
54
 (OMIM) Hypothalamic dysfunction 4 / 7739
55
 (OMIM) Gliosis of the white matter 1 / 7739
56
 (OMIM) Seizures, intractable, neonatal 1 / 7739
57
 (OMIM) Spasticity, distal 1 / 7739
58
 (HPO:0001522) Death in infancy Frequent [Orphanet] 275 / 7739
59
 (OMIM) Neuronal migration defect 4 / 7739
60
 (HPO:0002536) Abnormal cortical gyration Very frequent [Orphanet] 72 / 7739
61
 (OMIM) Thin optic nerves 2 / 7739
62
 (OMIM) Anterior pachygyria and posterior agyria 1 / 7739
63
 (HPO:0001274) Agenesis of corpus callosum 142 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females ...
Clinical Description OMIM Dobyns et al. (1999) recognized 5 children from 4 unrelated families with an almost identical disorder comprising lissencephaly with a posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset epilepsy, hypothalamic dysfunction ...
Genotype-Phenotype Correlations OMIM In a review of 29 males with ARX mutations, Kato et al. (2004) found that those with premature termination or nonsense mutations had brain malformation syndromes, including XLAG and Proud syndrome, whereas those with expansion of the polyalanine ...
Molecular genetics OMIM Kitamura et al. (2002) identified loss-of-function mutations in the ARX gene (300382) in individuals affected with XLAG and in some female relatives. Kitamura et al. (2002) suggested that this may have been the first incidence in which phenotypic ...