SSMED
MCID: SHR082
MIFTS: 25

Short Stature, Microcephaly, and Endocrine Dysfunction (SSMED)

Categories: Genetic diseases, Immune diseases

Aliases & Classifications for Short Stature, Microcephaly, and Endocrine Dysfunction

MalaCards integrated aliases for Short Stature, Microcephaly, and Endocrine Dysfunction:

Name: Short Stature, Microcephaly, and Endocrine Dysfunction 58 76 30 6
Ssmed 58 76
Stature, Short, Microcephaly, and Endocrine Dysfunction 41

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
endocrine and neurologic defects may become apparent later in life


HPO:

33
short stature, microcephaly, and endocrine dysfunction:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Short Stature, Microcephaly, and Endocrine Dysfunction

OMIM : 58 In patients with SSMED, short stature and microcephaly are apparent at birth, and there is progressive postnatal growth failure. Endocrine dysfunction, including hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus, is present in affected adults. Progressive ataxia has been reported in some patients, with onset ranging from the second to fifth decade of life. In addition, a few patients have developed tumors, suggesting that there may be a predisposition to tumorigenesis. In contrast to syndromes involving defects in other components of the nonhomologous end-joining (NHEJ) complex (see, e.g., 606593), no clinically overt immunodeficiency has been observed in SSMED, although laboratory analysis has revealed lymphopenia or borderline leukopenia in some patients (Murray et al., 2015; Bee et al., 2015; de Bruin et al., 2015; Guo et al., 2015). (616541)

MalaCards based summary : Short Stature, Microcephaly, and Endocrine Dysfunction, is also known as ssmed. An important gene associated with Short Stature, Microcephaly, and Endocrine Dysfunction is XRCC4 (X-Ray Repair Cross Complementing 4). Affiliated tissues include kidney, eye and thyroid, and related phenotypes are clinodactyly and cataract

UniProtKB/Swiss-Prot : 76 Short stature, microcephaly, and endocrine dysfunction: A disease characterized by short stature and microcephaly apparent at birth, progressive postnatal growth failure, and endocrine dysfunction. In affected adults endocrine features include hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus. Variable features observed in some patients are progressive ataxia, and lymphopenia or borderline leukopenia.

Related Diseases for Short Stature, Microcephaly, and Endocrine Dysfunction

Symptoms & Phenotypes for Short Stature, Microcephaly, and Endocrine Dysfunction

Human phenotypes related to Short Stature, Microcephaly, and Endocrine Dysfunction:

33 (show all 49)
# Description HPO Frequency HPO Source Accession
1 clinodactyly 33 occasional (7.5%) HP:0030084
2 cataract 33 occasional (7.5%) HP:0000518
3 sensorineural hearing impairment 33 occasional (7.5%) HP:0000407
4 pes cavus 33 occasional (7.5%) HP:0001761
5 dilated cardiomyopathy 33 occasional (7.5%) HP:0001644
6 truncal obesity 33 occasional (7.5%) HP:0001956
7 nystagmus 33 HP:0000639
8 diabetes mellitus 33 HP:0000819
9 hypothyroidism 33 HP:0000821
10 dysarthria 33 HP:0001260
11 inguinal hernia 33 HP:0000023
12 global developmental delay 33 HP:0001263
13 delayed speech and language development 33 HP:0000750
14 microcephaly 33 HP:0000252
15 short stature 33 HP:0004322
16 cognitive impairment 33 HP:0100543
17 anemia 33 HP:0001903
18 acanthosis nigricans 33 HP:0000956
19 ectopic kidney 33 HP:0000086
20 sensory neuropathy 33 HP:0000763
21 cryptorchidism 33 HP:0000028
22 intrauterine growth retardation 33 HP:0001511
23 dysmetria 33 HP:0001310
24 ventriculomegaly 33 HP:0002119
25 prominent nasal bridge 33 HP:0000426
26 deeply set eye 33 HP:0000490
27 apraxia 33 HP:0002186
28 lymphopenia 33 HP:0001888
29 broad nasal tip 33 HP:0000455
30 renal hypoplasia 33 HP:0000089
31 long face 33 HP:0000276
32 high forehead 33 HP:0000348
33 dysdiadochokinesis 33 HP:0002075
34 convex nasal ridge 33 HP:0000444
35 hypotelorism 33 HP:0000601
36 triangular face 33 HP:0000325
37 high pitched voice 33 HP:0001620
38 long nose 33 HP:0003189
39 sloping forehead 33 HP:0000340
40 cerebellar vermis atrophy 33 HP:0006855
41 micropenis 33 HP:0000054
42 misalignment of teeth 33 HP:0000692
43 unilateral renal agenesis 33 HP:0000122
44 insulin resistance 33 HP:0000855
45 short chin 33 HP:0000331
46 limb undergrowth 33 HP:0009826
47 broad-based gait 33 HP:0002136
48 simplified gyral pattern 33 HP:0009879
49 abnormal circulating lipid concentration 33 HP:0003119

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
hypotelorism
deep-set eyes
cataracts (rare)
slowing of eye pursuits

Neurologic Central Nervous System:
dysarthria
cognitive impairment
dysmetria
developmental delay
wide-based gait
more
Head And Neck Head:
microcephaly

Growth Height:
short stature

Genitourinary Kidneys:
ectopic kidney
unilateral renal agenesis
small kidneys

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Face:
long face
high forehead
triangular face
sloping forehead
small chin

Skeletal Limbs:
short limbs

Head And Neck Teeth:
malpositioned teeth

Metabolic Features:
dyslipidemia
mildly elevated glucose

Head And Neck Ears:
hearing loss, sensorineural (rare)

Skeletal Feet:
pes cavus (rare)

Muscle Soft Tissue:
hypotrophic type 2 muscle fibers

Immunology:
no clinical signs of immunodeficiency

Endocrine Features:
diabetes mellitus
hypothyroidism
insulin resistance
multinodular thyroid hypertrophy

Genitourinary External Genitalia Male:
inguinal hernia
micropenis

Skeletal Skull:
microcephaly

Skin Nails Hair Skin:
acanthosis nigricans

Neurologic Peripheral Nervous System:
sensory neuropathy

Head And Neck Nose:
broad nasal tip
long nose
beaked nose
high nasal bridge

Voice:
high-pitched voice

Skeletal Hands:
clinodactyly (rare)

Growth Other:
intrauterine growth failure
truncal obesity, mild (in some patients)

Chest Breasts:
absent thelarche

Cardiovascular Heart:
cardiomyopathy, dilated (rare)

Skin Nails Hair Hair:
fine, sparse hair

Hematology:
lymphopenia, mild
anemia, persistent

Neoplasia:
gastrointestinal stromal tumor of jejunum (rare)
thalamic glioma, low grade (rare)

Clinical features from OMIM:

616541

Drugs & Therapeutics for Short Stature, Microcephaly, and Endocrine Dysfunction

Search Clinical Trials , NIH Clinical Center for Short Stature, Microcephaly, and Endocrine Dysfunction

Genetic Tests for Short Stature, Microcephaly, and Endocrine Dysfunction

Genetic tests related to Short Stature, Microcephaly, and Endocrine Dysfunction:

# Genetic test Affiliating Genes
1 Short Stature, Microcephaly, and Endocrine Dysfunction 30 XRCC4

Anatomical Context for Short Stature, Microcephaly, and Endocrine Dysfunction

MalaCards organs/tissues related to Short Stature, Microcephaly, and Endocrine Dysfunction:

42
Kidney, Eye, Thyroid

Publications for Short Stature, Microcephaly, and Endocrine Dysfunction

Articles related to Short Stature, Microcephaly, and Endocrine Dysfunction:

# Title Authors Year
1
Mutations in the NHEJ component XRCC4 cause primordial dwarfism. ( 25728776 )
2015
2
Mutations in XRCC4 cause primary microcephaly, short stature and increased genomic instability. ( 25839420 )
2015
3
An XRCC4 splice mutation associated with severe short stature, gonadal failure, and early-onset metabolic syndrome. ( 25742519 )
2015
4
A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy. ( 25872942 )
2015
5
XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency. ( 26255102 )
2015
6
Genomic analysis of primordial dwarfism reveals novel disease genes. ( 24389050 )
2014
7
Response of motor complications in Cockayne syndrome to carbidopa-levodopa. ( 18695064 )
2008

Variations for Short Stature, Microcephaly, and Endocrine Dysfunction

UniProtKB/Swiss-Prot genetic disease variations for Short Stature, Microcephaly, and Endocrine Dysfunction:

76
# Symbol AA change Variation ID SNP ID
1 XRCC4 p.Trp43Arg VAR_075822 rs587779351
2 XRCC4 p.Arg161Gln VAR_075823 rs797045017

ClinVar genetic disease variations for Short Stature, Microcephaly, and Endocrine Dysfunction:

6 (show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 XRCC4 NM_003401.4(XRCC4): c.127T> C (p.Trp43Arg) single nucleotide variant Pathogenic rs587779351 GRCh38 Chromosome 5, 83105046: 83105046
2 XRCC4 NM_003401.4(XRCC4): c.127T> C (p.Trp43Arg) single nucleotide variant Pathogenic rs587779351 GRCh37 Chromosome 5, 82400865: 82400865
3 XRCC4 NM_022550.3(XRCC4): c.25del (p.His9Thrfs) deletion Pathogenic rs869320677 GRCh38 Chromosome 5, 83104944: 83104944
4 XRCC4 NM_022550.3(XRCC4): c.25del (p.His9Thrfs) deletion Pathogenic rs869320677 GRCh37 Chromosome 5, 82400763: 82400763
5 XRCC4 NM_022406.3(XRCC4): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs797045016 GRCh37 Chromosome 5, 82554426: 82554426
6 XRCC4 NM_022406.3(XRCC4): c.823C> T (p.Arg275Ter) single nucleotide variant Pathogenic rs797045016 GRCh38 Chromosome 5, 83258607: 83258607
7 XRCC4 NM_022550.3(XRCC4): c.-10-1G> T single nucleotide variant Pathogenic rs869320678 GRCh37 Chromosome 5, 82400728: 82400728
8 XRCC4 NM_022550.3(XRCC4): c.-10-1G> T single nucleotide variant Pathogenic rs869320678 GRCh38 Chromosome 5, 83104909: 83104909
9 XRCC4 NM_022406.3(XRCC4): c.673C> T (p.Arg225Ter) single nucleotide variant Pathogenic rs768825050 GRCh38 Chromosome 5, 83204849: 83204849
10 XRCC4 NM_022406.3(XRCC4): c.673C> T (p.Arg225Ter) single nucleotide variant Pathogenic rs768825050 GRCh37 Chromosome 5, 82500668: 82500668
11 XRCC4 NM_022406.3(XRCC4): c.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic rs779773463 GRCh38 Chromosome 5, 83195935: 83195935
12 XRCC4 NM_022406.3(XRCC4): c.481C> T (p.Arg161Ter) single nucleotide variant Pathogenic rs779773463 GRCh37 Chromosome 5, 82491754: 82491754
13 XRCC4 NM_022406.3(XRCC4): c.246T> G (p.Asp82Glu) single nucleotide variant Pathogenic rs879255258 GRCh37 Chromosome 5, 82406953: 82406953
14 XRCC4 NM_022406.3(XRCC4): c.246T> G (p.Asp82Glu) single nucleotide variant Pathogenic rs879255258 GRCh38 Chromosome 5, 83111134: 83111134
15 XRCC4 NM_022406.3(XRCC4): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs797045017 GRCh37 Chromosome 5, 82491755: 82491755
16 XRCC4 NM_022406.3(XRCC4): c.482G> A (p.Arg161Gln) single nucleotide variant Pathogenic rs797045017 GRCh38 Chromosome 5, 83195936: 83195936
17 XRCC4 NM_022550.3(XRCC4): c.760delG (p.Asp254Metfs) deletion Pathogenic rs879255259 GRCh37 Chromosome 5, 82554363: 82554363
18 XRCC4 NM_022550.3(XRCC4): c.760delG (p.Asp254Metfs) deletion Pathogenic rs879255259 GRCh38 Chromosome 5, 83258544: 83258544

Expression for Short Stature, Microcephaly, and Endocrine Dysfunction

Search GEO for disease gene expression data for Short Stature, Microcephaly, and Endocrine Dysfunction.

Pathways for Short Stature, Microcephaly, and Endocrine Dysfunction

GO Terms for Short Stature, Microcephaly, and Endocrine Dysfunction

Sources for Short Stature, Microcephaly, and Endocrine Dysfunction

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....