SIDDT
MCID: SDD002
MIFTS: 33

Sudden Infant Death with Dysgenesis of the Testes Syndrome (SIDDT)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Sudden Infant Death with Dysgenesis of the Testes Syndrome

MalaCards integrated aliases for Sudden Infant Death with Dysgenesis of the Testes Syndrome:

Name: Sudden Infant Death with Dysgenesis of the Testes Syndrome 57 20 43 72 36 29 13 6 39 70
Siddt 57 20 43 58 72
Sudden Infant Death-Dysgenesis of the Testes Syndrome 20 58
Sudden Infant Death - Dysgenesis of the Testes 20

Characteristics:

Orphanet epidemiological data:

58
sudden infant death-dysgenesis of the testes syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile;

OMIM®:

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

Miscellaneous:
affected infants appear normal at birth
symptoms develop immediately after birth
death occurs before 12 months of age due to cardiorespiratory arrest


HPO:

31
sudden infant death with dysgenesis of the testes syndrome:
Onset and clinical course death in infancy
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare respiratory diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Sudden Infant Death with Dysgenesis of the Testes Syndrome

MedlinePlus Genetics : 43 Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is a rare condition that is fatal in the first year of life; its major features include abnormalities of the reproductive system in males, feeding difficulties, and breathing problems.Infants with SIDDT who are genetically male, with one X chromosome and one Y chromosome in each cell, have underdeveloped or abnormal testes. They may also have external genitalia that appear female or that do not look clearly male or clearly female (ambiguous genitalia). In affected infants who are genetically female, with two X chromosomes in each cell, development of the internal and external reproductive organs is normal.SIDDT is associated with abnormal development of the brain, particularly the brainstem, which is the part of the brain that is connected to the spinal cord. The brainstem regulates many basic body functions, including heart rate, breathing, eating, and sleeping. It also relays information about movement and the senses between the brain and the rest of the body. Many features of SIDDT appear to be related to brainstem malfunction, including a slow or uneven heart rate, abnormal breathing patterns, difficulty controlling body temperature, unusual tongue and eye movements, an exaggerated startle reflex to sudden lights or loud noises, and feeding difficulties. Affected infants also have an unusual cry that has been described as similar to the bleating of a goat, which is probably a result of abnormal nerve connections between the brain and the voicebox (larynx).The brainstem abnormalities lead to death in the first year of life, when affected infants suddenly stop breathing or their heart stops beating (cardiorespiratory arrest).

MalaCards based summary : Sudden Infant Death with Dysgenesis of the Testes Syndrome, also known as siddt, is related to sudden infant death syndrome and lymphopenia, and has symptoms including stridor An important gene associated with Sudden Infant Death with Dysgenesis of the Testes Syndrome is TSPYL1 (TSPY Like 1). Affiliated tissues include testes, brain and heart, and related phenotypes are hypothermia and sleep apnea

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 168593 Definition Sudden infant death with dysgenesis of the testes (SIDDT) syndrome is a lethal condition in infants with dysgenesis of testes. Epidemiology SIDDT syndrome has been described in 21 infants from nine separate sibships among the Old Order Amish. Clinical description Infants with SIDDT syndrome appear normal at birth except that they are often recognized by the unusual staccato sound of their cry. Within the first months of life, they develop signs of viscera-autonomic nerve dysfunction including bradycardia, hypothermia, severe gastroesophageal reflux, laryngospasm, bronchospasm, and abnormal cardiorespiratory patterns during sleep. XY males have testicular dysgenesis and ambiguous genitalia. Female sexual development is normal. Etiology SIDDT syndrome is caused by homozygous mutation in the testis-specific protein Y-like-1 gene, TSPYL1 on chromosome 6 (6q22.1-q22.31). Genetic counseling The syndrome follows an autosomal recessive pattern of inheritance. Prognosis Prognosis is very poor: infants die before 12 months of age of sudden cardiorespiratory arrest.

KEGG : 36 Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is an autosomal recessive syndrome that was first identified in an Old Order Amish community. Infants with SIDDT appear normal at birth, develop signs of visceral and autonomic dysfunction early in life, and die before 12 months of age of abrupt cardiorespiratory arrest. SIDDT was identified to be caused by loss of function mutations in the TSPYL1 gene.

UniProtKB/Swiss-Prot : 72 Sudden infant death with dysgenesis of the testes syndrome: Autosomal recessive disorder. Affected infants appear normal at birth, develop signs of visceroautonomic dysfunction early in life, and die before 12 months of age of abrupt cardiorespiratory arrest. Features included bradycardia, hypothermia, severe gastroesophageal reflux, laryngospasm, bronchospasm, and abnormal cardiorespiratory patterns during sleep. Genotypic males with SIDDT had fetal testicular dysgenesis and ambiguous genitalia, with findings such as intraabdominal testes, dysplastic testes, deficient fetal testosterone production, fusion and rugation of the gonadal sac, and partial development of the penile shaft. Female sexual development was normal. Affected infants had an unusual staccato cry, similar to the cry of a goat.

More information from OMIM: 608800

Related Diseases for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Diseases related to Sudden Infant Death with Dysgenesis of the Testes Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 sudden infant death syndrome 10.3
2 lymphopenia 10.3

Symptoms & Phenotypes for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Human phenotypes related to Sudden Infant Death with Dysgenesis of the Testes Syndrome:

58 31 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypothermia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002045
2 sleep apnea 58 31 hallmark (90%) Very frequent (99-80%) HP:0010535
3 gastroesophageal reflux 58 31 hallmark (90%) Very frequent (99-80%) HP:0002020
4 cryptorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000028
5 hypoplasia of penis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008736
6 ambiguous genitalia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000062
7 scrotal hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000046
8 cardiac arrest 58 31 hallmark (90%) Very frequent (99-80%) HP:0001695
9 abnormal autonomic nervous system physiology 31 hallmark (90%) HP:0012332
10 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
11 growth delay 58 31 frequent (33%) Frequent (79-30%) HP:0001510
12 ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000602
13 abnormality of the voice 58 31 frequent (33%) Frequent (79-30%) HP:0001608
14 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
15 dysautonomia 58 Very frequent (99-80%)
16 feeding difficulties in infancy 31 HP:0008872
17 arrhythmia 58 Very frequent (99-80%)
18 abnormality of the eye 31 HP:0000478
19 death in infancy 58 Very frequent (99-80%)
20 apnea 31 HP:0002104
21 abnormality of metabolism/homeostasis 31 HP:0001939
22 ambiguous genitalia, male 31 HP:0000033
23 abnormal pattern of respiration 58 Very frequent (99-80%)
24 stridor 31 HP:0010307
25 testicular dysgenesis 31 HP:0008715
26 cardiorespiratory arrest 31 HP:0006543
27 bradycardia 31 HP:0001662
28 tongue fasciculations 31 HP:0001308
29 laryngospasm 31 HP:0025425
30 bronchospasm 31 HP:0025428
31 partial development of the penile shaft 31 HP:0008708
32 dysplastic testes 31 HP:0008733
33 staccato cry 31 HP:0025431

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Genitourinary Internal Genitalia Male:
cryptorchidism
testicular dysgenesis
dysplastic testes
tortuous vascularity in the testes
arrested cell development in the testes
more
Abdomen Gastrointestinal:
feeding difficulties
gastroesophageal reflux, severe

Cardiovascular Heart:
bradycardia
variable heart rate (range 52-250 beats per minute)

Neurologic Central Nervous System:
tongue fasciculations
facial nerve weakness
visceroautonomic dysfunction
decreased upper extremity reflexes
hyperactive startle reflex
more
Respiratory Airways:
bronchospasm

Head And Neck Face:
facial nerve weakness

Genitourinary:
variable maturation of genitalia in males

Laboratory Abnormalities:
abnormal response to human chorionic gonadotropin indicates decreased testosterone

Genitourinary External Genitalia Male:
ambiguous genitalia
partial development of the penile shaft

Respiratory:
stridor
abnormal respiratory patterns
apnea (central and obstructive)

Head And Neck Mouth:
tongue fasciculations

Respiratory Larynx:
laryngospasm

Growth Other:
poor growth

Head And Neck Eyes:
ocular muscle palsies

Voice:
staccato cry ('goat-like')

Clinical features from OMIM®:

608800 (Updated 20-May-2021)

UMLS symptoms related to Sudden Infant Death with Dysgenesis of the Testes Syndrome:


stridor

Drugs & Therapeutics for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Search Clinical Trials , NIH Clinical Center for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Genetic Tests for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Genetic tests related to Sudden Infant Death with Dysgenesis of the Testes Syndrome:

# Genetic test Affiliating Genes
1 Sudden Infant Death with Dysgenesis of the Testes Syndrome 29 TSPYL1

Anatomical Context for Sudden Infant Death with Dysgenesis of the Testes Syndrome

MalaCards organs/tissues related to Sudden Infant Death with Dysgenesis of the Testes Syndrome:

40
Testes, Brain, Heart, Tongue, Eye, Spinal Cord, Testis

Publications for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Articles related to Sudden Infant Death with Dysgenesis of the Testes Syndrome:

# Title Authors PMID Year
1
Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function. 61 57 6
15273283 2004
2
Sudden infant death with dysgenesis of the testes syndrome in a non-Amish infant: A case report. 61
32885560 2020
3
Survey of disorders of sex development in a large cohort of patients with diverse Mendelian phenotypes. 61
32949114 2020
4
Variants in TSPYL1 are not associated with sudden infant death syndrome in a cohort of deceased infants from Switzerland. 61
25449952 2015
5
Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. 61
17160900 2007
6
Genetic investigation of the TSPYL1 gene in sudden infant death syndrome. 61
16418600 2006

Variations for Sudden Infant Death with Dysgenesis of the Testes Syndrome

ClinVar genetic disease variations for Sudden Infant Death with Dysgenesis of the Testes Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TSPYL1 TSPYL1, 1-BP INS, 457G Insertion Pathogenic 5385 GRCh37:
GRCh38:
2 TSPYL1 , DSE NM_003309.4(TSPYL1):c.723_724TG[1] (p.Val242fs) Microsatellite Pathogenic/Likely pathogenic 805870 rs775957625 GRCh37: 6:116600268-116600269
GRCh38: 6:116279105-116279106
3 TSPYL1 , DSE NM_003309.4(TSPYL1):c.236del (p.Gly79fs) Deletion Likely pathogenic 988762 GRCh37: 6:116600758-116600758
GRCh38: 6:116279595-116279595

Expression for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Search GEO for disease gene expression data for Sudden Infant Death with Dysgenesis of the Testes Syndrome.

Pathways for Sudden Infant Death with Dysgenesis of the Testes Syndrome

GO Terms for Sudden Infant Death with Dysgenesis of the Testes Syndrome

Biological processes related to Sudden Infant Death with Dysgenesis of the Testes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleosome assembly GO:0006334 8.62 TSPYL1 TSPY1

Molecular functions related to Sudden Infant Death with Dysgenesis of the Testes Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin binding GO:0003682 8.96 TSPYL1 TSPY1
2 histone binding GO:0042393 8.62 TSPYL1 TSPY1

Sources for Sudden Infant Death with Dysgenesis of the Testes Syndrome

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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