Alpha-thalassemia - intellectual deficit syndrome linked to chromosome 16

General Information (adopted from Orphanet):

Synonyms, Signs: MENTAL RETARDATION WITH HEMOGLOBIN H
ATR, DELETION-TYPE
ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, DELETION-TYPE
HEMOGLOBIN H-RELATED MENTAL RETARDATION
HBHR
ATR syndrome, deletion type
atr-16 syndrome
CHROMOSOME 16p DELETION SYNDROME
Alpha thalassemia - intellectual deficit syndrome, deletion type
Alpha thalassemia - retardation syndrome
ATR syndrome linked to chromosome 16
Number of Symptoms 71
OrphanetNr: 98791
OMIM Id: 141750
ICD-10: D56.0
UMLs: C0475813
MeSH:
MedDRA:
Snomed: 277918006

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Unknown
Not applicable
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Alpha-thalassemia-related diseases
 -Rare genetic disease
 -Rare hematologic disease
Partial deletion of the short arm of chromosome 16
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare genetic intellectual deficit with developmental anomaly
 -Rare genetic disease
Rare intellectual deficit with developmental anomaly
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000028) Cryptorchidism 347 / 7739
2
 (HPO:0000054) Micropenis 257 / 7739
3
 (HPO:0000047) Hypospadias Occasional [Orphanet] 250 / 7739
4
 (HPO:0000035) Abnormality of the testis Frequent [Orphanet] 296 / 7739
5
 (HPO:0000494) Downslanted palpebral fissures Frequent [Orphanet] 328 / 7739
6
 (HPO:0005280) Depressed nasal bridge 381 / 7739
7
 (HPO:0004425) Flat forehead 6 / 7739
8
 (HPO:0000286) Epicanthus Frequent [Orphanet] 371 / 7739
9
 (HPO:0000348) High forehead Frequent [Orphanet] 157 / 7739
10
 (HPO:0002007) Frontal bossing Occasional [Orphanet] 366 / 7739
11
 (HPO:0000277) Abnormality of the mandible Frequent [Orphanet] 394 / 7739
12
 (HPO:0000343) Long philtrum 262 / 7739
13
 (HPO:0000431) Wide nasal bridge Frequent [Orphanet] 290 / 7739
14
 (HPO:0000463) Anteverted nares 305 / 7739
15
 (HPO:0002705) High, narrow palate Frequent [Orphanet] 308 / 7739
16
 (HPO:0009891) Underdeveloped supraorbital ridges Occasional [Orphanet] 36 / 7739
17
 (HPO:0000470) Short neck Frequent [Orphanet] 345 / 7739
18
 (HPO:0000678) Dental crowding 65 / 7739
19
 (HPO:0000337) Broad forehead Frequent [Orphanet] 116 / 7739
20
 (HPO:0000218) High palate 356 / 7739
21
 (HPO:0000451) Triangular nasal tip 8 / 7739
22
 (HPO:0010808) Protruding tongue 28 / 7739
23
 (HPO:0100840) Aplasia/Hypoplasia of the eyebrow Occasional [Orphanet] 117 / 7739
24
 (HPO:0000158) Macroglossia 119 / 7739
25
 (HPO:0011800) Midface retrusion Frequent [Orphanet] 221 / 7739
26
 (HPO:0000252) Microcephaly Frequent [Orphanet] 832 / 7739
27
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
28
 (HPO:0000278) Retrognathia 100 / 7739
29
 (HPO:0000465) Webbed neck 81 / 7739
30
 (HPO:0000508) Ptosis 459 / 7739
31
 (HPO:0008551) Microtia 98 / 7739
32
 (HPO:0009906) Aplasia/Hypoplasia of the earlobes Frequent [Orphanet] 41 / 7739
33
 (HPO:0000357) Abnormal location of ears Frequent [Orphanet] 328 / 7739
34
 (HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 308 / 7739
35
 (HPO:0001250) Seizures Rare [HPO:probinson] 1245 / 7739
36
 (HPO:0001327) Photomyoclonic seizures 125 / 7739
37
 (HPO:0001249) Intellectual disability 1089 / 7739
38
 (HPO:0002558) Supernumerary nipple 40 / 7739
39
 (HPO:0006494) Aplasia/Hypoplasia involving bones of the feet Frequent [Orphanet] 69 / 7739
40
 (HPO:0009466) Radial deviation of finger 101 / 7739
41
 (HPO:0001555) Asymmetry of the thorax 15 / 7739
42
 (HPO:0001762) Talipes equinovarus Frequent [Orphanet] 309 / 7739
43
 (HPO:0000768) Pectus carinatum Frequent [Orphanet] 136 / 7739
44
 (HPO:0004322) Short stature Frequent [Orphanet] 1232 / 7739
45
 (HPO:0004325) Decreased body weight Frequent [Orphanet] 492 / 7739
46
 (HPO:0000978) Bruising susceptibility Frequent [Orphanet] 123 / 7739
47
 (HPO:0011648) Patent ductus arteriosus after birth at term 18 / 7739
48
 (HPO:0001643) Patent ductus arteriosus 228 / 7739
49
 (HPO:0011907) Reduced alpha/beta synthesis ratio 6 / 7739
50
 (HPO:0001935) Microcytic anemia Very frequent [Orphanet] 32 / 7739
51
 (HPO:0004840) Hypochromic microcytic anemia 15 / 7739
52
 (HPO:0011903) Hemoglobin H 3 / 7739
53
 (HPO:0011902) Abnormal hemoglobin Very frequent [Orphanet] 18 / 7739
54
 (HPO:0003220) Abnormality of chromosome stability Very frequent [Orphanet] 98 / 7739
55
 (HPO:0001252) Muscular hypotonia Frequent [Orphanet] 990 / 7739
56
 (HPO:0003394) Muscle cramps Occasional [Orphanet] 106 / 7739
57
 (HPO:0001324) Muscle weakness Frequent [Orphanet] 859 / 7739
58
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
59
 (OMIM) Clinodactyly of isolated digits 8 / 7739
60
 (HPO:0001466) Contiguous gene syndrome 8 / 7739
61
 (OMIM) Subtelomeric deletion of chromosome 16p 1 / 7739
62
 (OMIM) Obesity, mild (less common) 8 / 7739
63
 (OMIM) Hb H inclusions in red blood cells 1 / 7739
64
 (MedDRA:10040251) Serum ferritin normal 1 / 7739
65
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
66
 (OMIM) Alpha-thalassemia 1 / 7739
67
 (OMIM) Retrognathia, mild 3 / 7739
68
 (Orphanet:15360) Abnormally placed nipples 1 / 7739
69
 (OMIM) Mental retardation, mild to moderate 33 / 7739
70
 (OMIM) Wide, flat, broad forehead 1 / 7739
71
 (HPO:0003812) Phenotypic variability 129 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Weatherall et al. (1981) reported the association of hemoglobin H disease (Hb H; see alpha-thalassemias, 141800) and mental retardation in 3 unrelated patients of northern European descent.

Hjelle et al. (1982) described a somewhat similar case ...
Molecular genetics OMIM Pfeifer et al. (2000) stated that the SOX8 gene (605923) was found to be deleted in a patient with ATR-16 syndrome who carried a 2-Mb deletion on chromosome 16p13.3. Based on the high expression of SOX8 in the ...