MCID: SHR082
MIFTS: 22

Short Stature, Microcephaly, and Endocrine Dysfunction

Categories: Genetic 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 57 75 29 6
Ssmed 57 75
Stature, Short, Microcephaly, and Endocrine Dysfunction 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
short stature, microcephaly, and endocrine dysfunction:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Short Stature, Microcephaly, and Endocrine Dysfunction

OMIM : 57 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 eye, kidney and thyroid, and related phenotypes are clinodactyly and nystagmus

UniProtKB/Swiss-Prot : 75 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

Symptoms via clinical synopsis from OMIM:

57
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

GenitourinaryInternal GenitaliaMale:
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

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

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

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 29 XRCC4

Anatomical Context for Short Stature, Microcephaly, and Endocrine Dysfunction

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

41
Eye, Kidney, Thyroid

Publications for Short Stature, Microcephaly, and Endocrine Dysfunction

Variations for Short Stature, Microcephaly, and Endocrine Dysfunction

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

75
# 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.25delC (p.His9Thrfs) deletion Pathogenic rs869320677 GRCh38 Chromosome 5, 83104944: 83104944
4 XRCC4 NM_022550.3(XRCC4): c.25delC (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_022406.3(XRCC4): c.760delG (p.Asp254Metfs) deletion Pathogenic rs879255259 GRCh37 Chromosome 5, 82554363: 82554363
18 XRCC4 NM_022406.3(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 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
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44 MeSH
45 MESH via Orphanet
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55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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