Perrault Syndrome 1

General Information (adopted from Orphanet):

Synonyms, Signs: PRLTS1
Gonadal dysgenesis, XX type, with deafness
Ovarian dysgenesis with sensorineural deafness
PRLTS type-1 [IBIS]
Number of Symptoms 23
OrphanetNr:
OMIM Id: 233400
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
25956234 [IBIS]
Age of onset: Infancy
Childhood
Adolescent
Adult
20673864; 25956234 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Perrault Syndrome
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare genetic disease
 -Rare gynecologic or obstetric disease
 -Rare neurologic disease
 -Rare otorhinolaryngologic disease
 -Rare urogenital disease

Comment:

Perrault Syndrome 1 (PRLTS1) is a subtype / child of Perrault Syndrome. Mutations in HSD17B4 (= DBP, MFE-2, MPF-2, PRLTS1, SDR8C1) on chromosome 5q23.1, encoding the multifunctional peroxisomal enzyme 17 beta-hydroxysteroid dehydrogenase type 4 cause PRLTS1. The HSD17B4 enzyme is also known as DBP and is involved in fatty acid beta-oxidation and steroid metabolism (PMID:25956234). Mutations in HSD17B4 cause DBP deficiency (MIM 261515), an autosomal-recessive disorder of peroxisomal fatty acid beta-oxidation that is generally fatal within the first two years of life. Patients with classical DBP deficiency present with hypotonia and seizures by one month of age (PMID:20673864). DBP deficiency can be classified into three types, each based on which of the two DBP enzymatic activities are diminished. In type I, both hydratase and dehydrogenase activities are deficient, type II is a specific hydratase deficiency, and type III is a specific dehydrogenase deficiency. Different classes of HSD17B4 mutations are associated with each type of DBP deficiency. Type I deficiency is generally associated with nonsense mutations, frameshift mutations, or in-frame deletions of 20 or more residues in the dehydrogenase domain. In patients with type I deficiency, HSD17B4 protein is almost always undetectable in fibroblasts. Type II deficiency is associated with missense mutations or in-frame deletions in the hydratase domain, and type III deficiency is associated with missense mutations or single amino acid deletions in the dehydrogenase domain (PMID:20673864).

Symptom Information: Sort by abundance 

1
 (HPO:0001249) Intellectual disability 20673864 IBIS 1089 / 7739
2
 (HPO:0008724) Hypoplasia of the ovary 26970254 IBIS 6 / 7739
3
 (HPO:0000013) Hypoplasia of the uterus 20673864 IBIS 21 / 7739
4
 (HPO:0000815) Hypergonadotropic hypogonadism 26970254 IBIS 48 / 7739
5
 (HPO:0001271) Polyneuropathy 20673864 IBIS 56 / 7739
6
 (HPO:0001272) Cerebellar atrophy 20673864 IBIS 197 / 7739
7
 (OMIM) Peripheral polyneuropathy 20673864 IBIS 2 / 7739
8
 (HPO:0000505) Visual impairment 20673864 IBIS 297 / 7739
9
 (HPO:0008167) Very long chain fatty acid accumulation 20673864 IBIS 5 / 7739
10
 (HPO:0001252) Muscular hypotonia Very frequent [IBIS] 20673864 IBIS 990 / 7739
11
 (HPO:0009830) Peripheral neuropathy 25956234 IBIS 206 / 7739
12
 (HPO:0001251) Ataxia 25956234 IBIS 413 / 7739
13
 (HPO:0001263) Global developmental delay 20673864 IBIS 853 / 7739
14
 (HPO:0001250) Seizures Very frequent [IBIS] 20673864 IBIS 1245 / 7739
15
 (HPO:0000133) Gonadal dysgenesis Very frequent [IBIS] 25956234 IBIS 21 / 7739
16
 (HPO:0008209) Premature ovarian failure Very frequent [IBIS] 25956234 IBIS 28 / 7739
17
 (HPO:0001587) Primary ovarian failure Very frequent [IBIS] 26970254 IBIS 9 / 7739
18
 (HPO:0008222) Female infertility Very frequent [IBIS] 25956234 IBIS 7 / 7739
19
 (HPO:0003251) Male infertility Very frequent [IBIS] 25956234 IBIS 14 / 7739
20
 (HPO:0000407) Sensorineural hearing impairment Very frequent [IBIS] 25956234 IBIS 524 / 7739
21
 (OMIM) Decreased or absent D-bifunctional protein activity and protein 25956234 IBIS 2 / 7739
22
 (OMIM) Dysmorphic features 20673864 IBIS 6 / 7739
23
 (OMIM) Ovarian dysgenesis Very frequent [IBIS] 25956234 IBIS 7 / 7739

Associated genes:

HSD17B4;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Perrault syndrome is a sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement (summary ...
Clinical Description OMIM Perrault et al. (1951) described 2 sisters with a syndrome comprising sensorineural deafness and ovarian dysgenesis. The parents were cousins, suggesting autosomal recessive inheritance. Josso et al. (1963) restudied the sisters reported by Perrault et al. (1951) as ...
Molecular genetics OMIM Pierce et al. (2010) performed whole-exome sequencing of genomic DNA from 1 of the sisters with Perrault syndrome previously described by McCarthy and Opitz (1985) and Fiumara et al. (2004) and identified 2 rare variants in the HSD17B4 ...