Hoyeraal-Hreidarsson syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: CEREBELLAR HYPOPLASIA WITH PANCYTOPENIA, INCLUDED
GROWTH RETARDATION, PRENATAL, WITH PROGRESSIVE PANCYTOPENIA AND CEREBELLAR HYPOPLASIA, INCLUDED
HHS, INCLUDED
ZINSSER-COLE-ENGMAN SYNDROME HOYERAAL-HREIDARSSON SYNDROME, INCLUDED
DKCX
Progressive pancytopenia - immunodeficiency - cerebellar hypoplasia
Number of Symptoms 77
OrphanetNr: 3322
OMIM Id: 305000
ICD-10: D61.0
UMLs: C1846142
MeSH: C536068
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
Autosomal recessive
X-linked recessive
[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
Other immunodeficiency syndrome due to defects in adaptive immunity
 -Rare genetic disease
 -Rare immune disease
Rare constitutional medullar aplasia
 -Rare genetic disease
 -Rare hematologic 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:0001741) Phimosis 5 / 7739
2
 (HPO:0000085) Horseshoe kidney 39 / 7739
3
 (HPO:0008661) Urethral stenosis 9 / 7739
4
 (HPO:0008734) Decreased testicular size 105 / 7739
5
 (HPO:0000047) Hypospadias 250 / 7739
6
 (HPO:0000028) Cryptorchidism 347 / 7739
7
 (HPO:0000653) Sparse eyelashes 58 / 7739
8
 (HPO:0000252) Microcephaly Very frequent [Orphanet] 832 / 7739
9
 (HPO:0006480) Premature loss of teeth 23 / 7739
10
 (HPO:0011830) Abnormality of oral mucosa Frequent [Orphanet] 47 / 7739
11
 (HPO:0000670) Carious teeth 145 / 7739
12
 (HPO:0000498) Blepharitis 27 / 7739
13
 (HPO:0002745) Oral leukoplakia 17 / 7739
14
 (HPO:0000486) Strabismus 576 / 7739
15
 (HPO:0009926) Increased lacrimation 8 / 7739
16
 (HPO:0000509) Conjunctivitis 47 / 7739
17
 (HPO:0000648) Optic atrophy 238 / 7739
18
 (HPO:0000518) Cataract 454 / 7739
19
 (HPO:0001263) Global developmental delay 25 % [HPO:skoehler] 853 / 7739
20
 (HPO:0001251) Ataxia rare [HPO:skoehler] 413 / 7739
21
 (HPO:0002066) Gait ataxia Occasional [Orphanet] 327 / 7739
22
 (HPO:0001328) Specific learning disability 114 / 7739
23
 (HPO:0001276) Hypertonia Frequent [Orphanet] 317 / 7739
24
 (HPO:0001249) Intellectual disability 1089 / 7739
25
 (HPO:0001315) Reduced tendon reflexes Occasional [Orphanet] 160 / 7739
26
 (HPO:0002514) Cerebral calcification Occasional [Orphanet] 89 / 7739
27
 (HPO:0000939) Osteoporosis 129 / 7739
28
 (HPO:0001394) Cirrhosis 102 / 7739
29
 (HPO:0002043) Esophageal stricture 7 / 7739
30
 (HPO:0005212) Anal mucosal leukoplakia 1 / 7739
31
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 492 / 7739
32
 (HPO:0001511) Intrauterine growth retardation Very frequent [Orphanet] 358 / 7739
33
 (HPO:0004322) Short stature Very frequent [Orphanet] 1232 / 7739
34
 (HPO:0005599) Hypopigmentation of hair Frequent [Orphanet] 38 / 7739
35
 (HPO:0000975) Hyperhidrosis 64 / 7739
36
 (HPO:0001597) Abnormality of the nail Frequent [Orphanet] 115 / 7739
37
 (HPO:0001807) Ridged nail 20 / 7739
38
 (HPO:0002165) Pterygium of nails 2 / 7739
39
 (HPO:0002216) Premature graying of hair 43 / 7739
40
 (HPO:0001596) Alopecia 162 / 7739
41
 (HPO:0002860) Squamous cell carcinoma 18 / 7739
42
 (HPO:0001809) Split nail 2 / 7739
43
 (HPO:0008404) Nail dystrophy 89 / 7739
44
 (HPO:0004334) Dermal atrophy 34 / 7739
45
 (HPO:0100678) Premature skin wrinkling Frequent [Orphanet] 25 / 7739
46
 (HPO:0001933) Subcutaneous hemorrhage Very frequent [Orphanet] 50 / 7739
47
 (HPO:0001006) Hypotrichosis Frequent [Orphanet] 219 / 7739
48
 (HPO:0000953) Hyperpigmentation of the skin Frequent [Orphanet] 75 / 7739
49
 (HPO:0007427) Reticulated skin pigmentation 7 / 7739
50
 (HPO:0001881) Abnormality of leukocytes Occasional [Orphanet] 6 / 7739
51
 (HPO:0005528) Bone marrow hypocellularity 31 / 7739
52
 (HPO:0012189) Hodgkin lymphoma 5 / 7739
53
 (HPO:0004808) Acute myeloid leukemia 14 / 7739
54
 (HPO:0002863) Myelodysplasia 30 / 7739
55
 (HPO:0001873) Thrombocytopenia Very frequent [Orphanet] 224 / 7739
56
 (HPO:0001876) Pancytopenia Occasional [Orphanet] 89 / 7739
57
 (HPO:0001928) Abnormality of coagulation Frequent [Orphanet] 44 / 7739
58
 (HPO:0001882) Leukopenia 51 / 7739
59
 (HPO:0001903) Anemia Frequent [Orphanet] 289 / 7739
60
 (HPO:0002206) Pulmonary fibrosis 51 / 7739
61
 (HPO:0002091) Restrictive ventilatory defect 46 / 7739
62
 (HPO:0002664) Neoplasm Occasional [Orphanet] 111 / 7739
63
 (HPO:0002721) Immunodeficiency 97 / 7739
64
 (HPO:0010978) Abnormality of immune system physiology Very frequent [Orphanet] 148 / 7739
65
 (MedDRA:10030901) Opportunistic infection 1 / 7739
66
 (OMIM) Complete nail loss 1 / 7739
67
 (HPO:0001321) Cerebellar hypoplasia rare [HPO:skoehler] 114 / 7739
68
 (HPO:0002119) Ventriculomegaly Frequent [Orphanet] 253 / 7739
69
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
70
 (OMIM) Reticulated skin pigmentation, predominantly on face, neck, chest, arms (94% male patients) 1 / 7739
71
 (OMIM) Conjunctival leukoplakia 1 / 7739
72
 (HPO:0002120) Cerebral cortical atrophy Frequent [Orphanet] 187 / 7739
73
 (OMIM) Increased chromosomal rearrangements (bone marrow and fibroblast culture) 1 / 7739
74
 (HPO:0001419) X-linked recessive inheritance 189 / 7739
75
 (OMIM) Reduced diffusion capacity 8 / 7739
76
 (HPO:0002334) Abnormality of the cerebellar vermis Very frequent [Orphanet] 137 / 7739
77
 (OMIM) Longitudinal splitting 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Dyskeratosis congenita is classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. It is characterized by short telomeres. Progressive bone marrow failure occurs in over 80% of cases and is ...
Clinical Description OMIM Milgrom et al. (1964) described a black male with dyskeratosis congenita. They pointed out that the 2 serious complications are anemia and cancer, which can develop in the leukoplakia of the anus or mouth or in the skin. ...
Molecular genetics OMIM In patients with X-linked DKC, Heiss et al. (1998) identified 5 different mutations in the DKC1 gene (300126.0001-300126.0005). Three families had previously been reported: Connor et al. (1986) (P40R; 300126.0003); Dokal et al. (1992) (G402Q; 300126.0005); and Devriendt ...