ACRDYS2
MCID: ACR119
MIFTS: 29

Acrodysostosis 2 with or Without Hormone Resistance (ACRDYS2)

Categories: Bone diseases, Endocrine diseases, Genetic diseases, Metabolic diseases

Aliases & Classifications for Acrodysostosis 2 with or Without Hormone Resistance

MalaCards integrated aliases for Acrodysostosis 2 with or Without Hormone Resistance:

Name: Acrodysostosis 2 with or Without Hormone Resistance 57 70
Acrodysostosis 2, with or Without Hormone Resistance 57 72 29 13 6
Acrdys2 57 72
Acrodysostosis, with/without Hormone Resistance, Type 2 39
Acrodysostosis 70

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth


HPO:

31
acrodysostosis 2 with or without hormone resistance:
Inheritance autosomal dominant inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Acrodysostosis 2 with or Without Hormone Resistance

UniProtKB/Swiss-Prot : 72 Acrodysostosis 2, with or without hormone resistance: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.

MalaCards based summary : Acrodysostosis 2 with or Without Hormone Resistance, is also known as acrodysostosis 2, with or without hormone resistance. An important gene associated with Acrodysostosis 2 with or Without Hormone Resistance is PDE4D (Phosphodiesterase 4D). Affiliated tissues include smooth muscle and bone, and related phenotypes are intellectual disability and diabetes mellitus

OMIM® : 57 Acrodysostosis-2 is a rare skeletal dysplasia characterized by brachydactyly, facial dysostosis, and spinal stenosis. Many patients have intellectual disability and some have hormone resistance (summary by Michot et al., 2012 and Lee et al., 2012). For a discussion of genetic heterogeneity of acrodysostosis, see ACRDYS1 (101800). (614613) (Updated 20-May-2021)

Related Diseases for Acrodysostosis 2 with or Without Hormone Resistance

Diseases in the Acrodysostosis 1 with or Without Hormone Resistance family:

Acrodysostosis 2 with or Without Hormone Resistance

Symptoms & Phenotypes for Acrodysostosis 2 with or Without Hormone Resistance

Human phenotypes related to Acrodysostosis 2 with or Without Hormone Resistance:

31 (show all 30)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 hallmark (90%) HP:0001249
2 diabetes mellitus 31 occasional (7.5%) HP:0000819
3 intrauterine growth retardation 31 occasional (7.5%) HP:0001511
4 congenital hypothyroidism 31 occasional (7.5%) HP:0000851
5 mild short stature 31 occasional (7.5%) HP:0003502
6 global developmental delay 31 HP:0001263
7 depressed nasal bridge 31 HP:0005280
8 mandibular prognathia 31 HP:0000303
9 increased intracranial pressure 31 HP:0002516
10 delayed speech and language development 31 HP:0000750
11 short nose 31 HP:0003196
12 anteverted nares 31 HP:0000463
13 cryptorchidism 31 HP:0000028
14 autism 31 HP:0000717
15 obesity 31 HP:0001513
16 blue irides 31 HP:0000635
17 brachydactyly 31 HP:0001156
18 spinal canal stenosis 31 HP:0003416
19 malar flattening 31 HP:0000272
20 hypospadias 31 HP:0000047
21 round face 31 HP:0000311
22 midface retrusion 31 HP:0011800
23 short metacarpal 31 HP:0010049
24 accelerated skeletal maturation 31 HP:0005616
25 cone-shaped epiphysis 31 HP:0010579
26 red hair 31 HP:0002297
27 hyperactivity 31 HP:0000752
28 short phalanx of finger 31 HP:0009803
29 short metatarsal 31 HP:0010743
30 fair hair 31 HP:0002286

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Nose:
depressed nasal bridge
anteverted nares
nasal hypoplasia

Neurologic Behavioral Psychiatric Manifestations:
autism
hyperactivity

Genitourinary External Genitalia Male:
hypospadias

Skin Nails Hair Hair:
red hair
blond hair

Skeletal Hands:
short metacarpals
short phalanges
cone-shaped epiphyses
brachydactyly, severe

Head And Neck Eyes:
blue eyes

Skeletal Spine:
spinal stenosis
lack of normal lumbar interpediculate flare

Growth Other:
intrauterine growth retardation (rare)

Endocrine Features:
increased serum pth, mild
diabetes mellitus (1 patient)
hypothyroidism, congenital (1 patient)

Genitourinary Internal Genitalia Male:
cryptorchidism

Growth Weight:
obesity

Head And Neck Face:
round face
midface hypoplasia
malar hypoplasia
prominent mandible
facial dysostosis
more
Skeletal:
advanced bone age
acrodysostosis

Skeletal Feet:
short phalanges
short metatarsals
brachydactyly, severe, with sparing of the big toe

Neurologic Central Nervous System:
speech delay
delayed psychomotor development
learning disabilities
intellectual disability (in most patients)

Growth Height:
short stature, mild (in some)

Cardiovascular Vascular:
intracranial hypertension (2 of 7 patients)
intracranial thrombosis (2 of 7 patients)

Clinical features from OMIM®:

614613 (Updated 20-May-2021)

Drugs & Therapeutics for Acrodysostosis 2 with or Without Hormone Resistance

Search Clinical Trials , NIH Clinical Center for Acrodysostosis 2 with or Without Hormone Resistance

Genetic Tests for Acrodysostosis 2 with or Without Hormone Resistance

Genetic tests related to Acrodysostosis 2 with or Without Hormone Resistance:

# Genetic test Affiliating Genes
1 Acrodysostosis 2, with or Without Hormone Resistance 29 PDE4D

Anatomical Context for Acrodysostosis 2 with or Without Hormone Resistance

MalaCards organs/tissues related to Acrodysostosis 2 with or Without Hormone Resistance:

40
Smooth Muscle, Bone

Publications for Acrodysostosis 2 with or Without Hormone Resistance

Articles related to Acrodysostosis 2 with or Without Hormone Resistance:

# Title Authors PMID Year
1
Different mutations in PDE4D associated with developmental disorders with mirror phenotypes. 6 57
24203977 2014
2
Identification of novel mutations confirms PDE4D as a major gene causing acrodysostosis. 57 6
23033274 2013
3
Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. 57 6
22464250 2012
4
Radiographic findings and Gs-alpha bioactivity studies and mutation screening in acrodysostosis indicate a different etiology from pseudohypoparathyroidism. 57 6
11200992 2001
5
Exome sequencing identifies PDE4D mutations in acrodysostosis. 57
22464252 2012
6
Expression, intracellular distribution and basis for lack of catalytic activity of the PDE4A7 isoform encoded by the human PDE4A cAMP-specific phosphodiesterase gene. 6
15025561 2004
7
Cyclic AMP-dependent transcriptional up-regulation of phosphodiesterase 4D5 in human airway smooth muscle cells. Identification and characterization of a novel PDE4D5 promoter. 6
12121997 2002
8
Mutations causing acrodysostosis-2 facilitate activation of phosphodiesterase 4D3. 61
29016851 2017

Variations for Acrodysostosis 2 with or Without Hormone Resistance

ClinVar genetic disease variations for Acrodysostosis 2 with or Without Hormone Resistance:

6 (show top 50) (show all 147)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PDE4D NM_001104631.2(PDE4D):c.673C>A (p.Pro225Thr) SNV Pathogenic 30035 rs397514464 GRCh37: 5:58489337-58489337
GRCh38: 5:59193511-59193511
2 PDE4D NM_001104631.2(PDE4D):c.677T>C (p.Phe226Ser) SNV Pathogenic 30036 rs397514465 GRCh37: 5:58489333-58489333
GRCh38: 5:59193507-59193507
3 PDE4D NM_001104631.2(PDE4D):c.568T>G (p.Ser190Ala) SNV Pathogenic 30037 rs397514466 GRCh37: 5:58511682-58511682
GRCh38: 5:59215856-59215856
4 PDE4D NM_001104631.2(PDE4D):c.1759A>C (p.Thr587Pro) SNV Pathogenic 30038 rs397514467 GRCh37: 5:58272248-58272248
GRCh38: 5:58976421-58976421
5 PDE4D NM_001104631.2(PDE4D):c.682C>G (p.Gln228Glu) SNV Pathogenic 30039 rs397514468 GRCh37: 5:58489328-58489328
GRCh38: 5:59193502-59193502
6 PDE4D NM_001104631.2(PDE4D):c.1952A>C (p.Glu651Ala) SNV Pathogenic 30040 rs387906744 GRCh37: 5:58271545-58271545
GRCh38: 5:58975718-58975718
7 PDE4D NM_001104631.2(PDE4D):c.2018G>A (p.Gly673Asp) SNV Pathogenic 30041 rs397514469 GRCh37: 5:58270903-58270903
GRCh38: 5:58975076-58975076
8 PDE4D NM_001104631.2(PDE4D):c.911C>T (p.Ala304Val) SNV Pathogenic 40064 rs397515433 GRCh37: 5:58334696-58334696
GRCh38: 5:59038869-59038869
9 PDE4D NM_001104631.2(PDE4D):c.677T>G (p.Phe226Cys) SNV Pathogenic 101052 rs397514465 GRCh37: 5:58489333-58489333
GRCh38: 5:59193507-59193507
10 PDE4D NM_001104631.2(PDE4D):c.2033T>C (p.Ile678Thr) SNV Pathogenic 101053 rs587777188 GRCh37: 5:58270888-58270888
GRCh38: 5:58975061-58975061
11 PDE4D NM_001104631.2(PDE4D):c.1762A>G (p.Met588Val) SNV Pathogenic 436281 rs1554033934 GRCh37: 5:58272245-58272245
GRCh38: 5:58976418-58976418
12 PDE4D NM_001104631.2(PDE4D):c.569C>T (p.Ser190Phe) SNV Likely pathogenic 982782 GRCh37: 5:58511681-58511681
GRCh38: 5:59215855-59215855
13 PDE4D NM_001104631.2(PDE4D):c.2051A>G (p.Glu684Gly) SNV Likely pathogenic 989238 GRCh37: 5:58270870-58270870
GRCh38: 5:58975043-58975043
14 PDE4D NM_001104631.2(PDE4D):c.1774A>C (p.Lys592Gln) SNV Uncertain significance 989239 GRCh37: 5:58272233-58272233
GRCh38: 5:58976406-58976406
15 overlap with 3 genes Deletion Uncertain significance 560134 GRCh37: 5:59768330-60020422
GRCh38: 5:60472503-60724595
16 PDE4D NM_001104631.2(PDE4D):c.1476T>G (p.Ile492Met) SNV Uncertain significance 932066 GRCh37: 5:58284396-58284396
GRCh38: 5:58988569-58988569
17 PDE4D NM_001104631.2(PDE4D):c.1542G>C (p.Leu514=) SNV Uncertain significance 353990 rs375617990 GRCh37: 5:58284330-58284330
GRCh38: 5:58988503-58988503
18 PDE4D NM_001104631.2(PDE4D):c.240C>G (p.Pro80=) SNV Uncertain significance 735008 rs1345148257 GRCh37: 5:59189210-59189210
GRCh38: 5:59893383-59893383
19 PDE4D NM_001104631.2(PDE4D):c.2366T>A (p.Val789Glu) SNV Uncertain significance 904243 GRCh37: 5:58270555-58270555
GRCh38: 5:58974728-58974728
20 PDE4D NM_001104631.2(PDE4D):c.794A>C (p.Lys265Thr) SNV Uncertain significance 904303 GRCh37: 5:58476435-58476435
GRCh38: 5:59180609-59180609
21 PDE4D NM_001104631.2(PDE4D):c.225G>A (p.Pro75=) SNV Uncertain significance 904306 GRCh37: 5:59189225-59189225
GRCh38: 5:59893398-59893398
22 PDE4D NM_001104631.2(PDE4D):c.*5201G>A SNV Uncertain significance 904839 GRCh37: 5:58265290-58265290
GRCh38: 5:58969463-58969463
23 PDE4D NM_001104631.2(PDE4D):c.*4981C>G SNV Uncertain significance 904840 GRCh37: 5:58265510-58265510
GRCh38: 5:58969683-58969683
24 PDE4D NM_001104631.2(PDE4D):c.*3325T>C SNV Uncertain significance 904906 GRCh37: 5:58267166-58267166
GRCh38: 5:58971339-58971339
25 PDE4D NM_001104631.2(PDE4D):c.*3210A>G SNV Uncertain significance 904907 GRCh37: 5:58267281-58267281
GRCh38: 5:58971454-58971454
26 PDE4D NM_001104631.2(PDE4D):c.*3028A>G SNV Uncertain significance 904908 GRCh37: 5:58267463-58267463
GRCh38: 5:58971636-58971636
27 PDE4D NM_001104631.2(PDE4D):c.*3875G>A SNV Uncertain significance 353927 rs886060704 GRCh37: 5:58266616-58266616
GRCh38: 5:58970789-58970789
28 PDE4D NM_001104631.2(PDE4D):c.*1778T>C SNV Uncertain significance 904969 GRCh37: 5:58268713-58268713
GRCh38: 5:58972886-58972886
29 PDE4D NM_001104631.2(PDE4D):c.*1729G>C SNV Uncertain significance 904970 GRCh37: 5:58268762-58268762
GRCh38: 5:58972935-58972935
30 PDE4D NM_001104631.2(PDE4D):c.2355A>C (p.Glu785Asp) SNV Uncertain significance 905026 GRCh37: 5:58270566-58270566
GRCh38: 5:58974739-58974739
31 PDE4D NM_001104631.2(PDE4D):c.2260A>G (p.Ser754Gly) SNV Uncertain significance 905027 GRCh37: 5:58270661-58270661
GRCh38: 5:58974834-58974834
32 PDE4D NM_001104631.2(PDE4D):c.1804C>T (p.Leu602Phe) SNV Uncertain significance 905028 GRCh37: 5:58272203-58272203
GRCh38: 5:58976376-58976376
33 PDE4D NM_001104631.2(PDE4D):c.1707+12A>C SNV Uncertain significance 905029 GRCh37: 5:58273006-58273006
GRCh38: 5:58977179-58977179
34 PDE4D NM_001104631.2(PDE4D):c.*4886A>C SNV Uncertain significance 906455 GRCh37: 5:58265605-58265605
GRCh38: 5:58969778-58969778
35 PDE4D NM_001104631.2(PDE4D):c.*4727C>G SNV Uncertain significance 906456 GRCh37: 5:58265764-58265764
GRCh38: 5:58969937-58969937
36 PDE4D NM_001104631.2(PDE4D):c.*4703A>G SNV Uncertain significance 906457 GRCh37: 5:58265788-58265788
GRCh38: 5:58969961-58969961
37 PDE4D NM_001104631.2(PDE4D):c.*2841A>C SNV Uncertain significance 906503 GRCh37: 5:58267650-58267650
GRCh38: 5:58971823-58971823
38 PDE4D NM_001104631.2(PDE4D):c.*2604A>C SNV Uncertain significance 906504 GRCh37: 5:58267887-58267887
GRCh38: 5:58972060-58972060
39 PDE4D NM_001104631.2(PDE4D):c.*1572A>G SNV Uncertain significance 906554 GRCh37: 5:58268919-58268919
GRCh38: 5:58973092-58973092
40 PDE4D NM_001104631.2(PDE4D):c.*1295G>A SNV Uncertain significance 906555 GRCh37: 5:58269196-58269196
GRCh38: 5:58973369-58973369
41 PDE4D NM_001104631.2(PDE4D):c.1577A>G (p.Asn526Ser) SNV Uncertain significance 906614 GRCh37: 5:58273148-58273148
GRCh38: 5:58977321-58977321
42 PDE4D NM_001104631.2(PDE4D):c.1333A>G (p.Ile445Val) SNV Uncertain significance 906615 GRCh37: 5:58285701-58285701
GRCh38: 5:58989874-58989874
43 PDE4D NM_001104631.2(PDE4D):c.1274A>C (p.His425Pro) SNV Uncertain significance 906616 GRCh37: 5:58286644-58286644
GRCh38: 5:58990817-58990817
44 PDE4D NM_001104631.2(PDE4D):c.*4529C>T SNV Uncertain significance 907449 GRCh37: 5:58265962-58265962
GRCh38: 5:58970135-58970135
45 PDE4D NM_001104631.2(PDE4D):c.*4524C>T SNV Uncertain significance 907450 GRCh37: 5:58265967-58265967
GRCh38: 5:58970140-58970140
46 PDE4D NM_001104631.2(PDE4D):c.*535A>G SNV Uncertain significance 907570 GRCh37: 5:58269956-58269956
GRCh38: 5:58974129-58974129
47 PDE4D NM_001104631.2(PDE4D):c.1189-4C>G SNV Uncertain significance 907636 GRCh37: 5:58286733-58286733
GRCh38: 5:58990906-58990906
48 PDE4D NM_001104631.2(PDE4D):c.1188+15A>G SNV Uncertain significance 907637 GRCh37: 5:58287644-58287644
GRCh38: 5:58991817-58991817
49 PDE4D NM_001104631.2(PDE4D):c.2179C>T (p.Arg727Trp) SNV Uncertain significance 587609 rs759832724 GRCh37: 5:58270742-58270742
GRCh38: 5:58974915-58974915
50 PDE4D NM_001104631.2(PDE4D):c.*2003T>C SNV Uncertain significance 353953 rs577458431 GRCh37: 5:58268488-58268488
GRCh38: 5:58972661-58972661

UniProtKB/Swiss-Prot genetic disease variations for Acrodysostosis 2 with or Without Hormone Resistance:

72 (show all 12)
# Symbol AA change Variation ID SNP ID
1 PDE4D p.Ser190Ala VAR_068242 rs397514466
2 PDE4D p.Pro225Thr VAR_068243 rs397514464
3 PDE4D p.Phe226Ser VAR_068244 rs397514465
4 PDE4D p.Thr587Pro VAR_068245 rs397514467
5 PDE4D p.Ala227Ser VAR_069448
6 PDE4D p.Gln228Glu VAR_069449 rs397514468
7 PDE4D p.Ser301Thr VAR_069450
8 PDE4D p.Ala304Val VAR_069451 rs397515433
9 PDE4D p.Val329Ala VAR_069452
10 PDE4D p.Glu590Ala VAR_069453
11 PDE4D p.Gly673Asp VAR_069454 rs397514469
12 PDE4D p.Ile678Thr VAR_069455 rs587777188

Expression for Acrodysostosis 2 with or Without Hormone Resistance

Search GEO for disease gene expression data for Acrodysostosis 2 with or Without Hormone Resistance.

Pathways for Acrodysostosis 2 with or Without Hormone Resistance

GO Terms for Acrodysostosis 2 with or Without Hormone Resistance

Sources for Acrodysostosis 2 with or Without Hormone Resistance

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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