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PURA-related neurodevelopmental disorders

PURA-related neurodevelopmental disorders
PURA-related neurodevelopmental disorders

Clinical characteristics. PURA-related neurodevelopmental disorders include PURA syndrome, caused by a heterozygous pathogenic sequence variant in PURA, and 5q31.3 deletion syndrome, caused by a genomic 5q31.3 deletion encompassing all or part of PURA. PURA-related neurodevelopmental disorders are characterized by moderate to severe neurodevelopmental delay with absence of speech in most and lack of independent ambulation in many. Early-onset problems can include hypotonia, hypothermia, hypersomnolence, feeding difficulties, excessive hiccups, recurrent central and obstructive apneas, epileptic seizures, abnormal non-epileptic movements (dystonia, dyskinesia, and dysconjugate eye movements), and abnormal vision. Congenital heart defects, urogenital malformations, skeletal abnormalities, and endocrine disorders occur, but are less common.

Diagnosis/testing. The diagnosis of a PURA-related neurodevelopmental disorder is established in a proband with either a heterozygous PURA pathogenic sequence variant (90% of affected individuals) or a non-recurrent deletion of 5q31.3 that encompasses all or part of PURA (10%).

Management. Treatment of manifestations: Ongoing routine care by a multidisciplinary team. Treatment and/or therapy for developmental delays; neurologic findings (hypotonia, seizures, abnormal movements); feeding difficulties; apnea; visual impairment; and malformations of the heart, urogenital tract, and skeleton.

Surveillance: Long-term follow up to assess psychomotor development, seizures or suspected seizures, vision, feeding for dysphagia, and musculoskeletal complications (hip dysplasia and scoliosis).

Genetic counseling. PURA-related neurodevelopmental disorders, caused by either a heterozygous PURA pathogenic sequence variant or a 5q31.3 deletion encompassing all or part of PURA are inherited in an autosomal dominant manner. In almost all probands with a PURA pathogenic sequence variant the sequence variant is de novo; to date, all reported 5q31.3 deletions have been de novo. For parents of an affected child, the risk to future pregnancies is presumed to be low, as a de novo genetic alteration involving PURA is most likely in the proband. However, parents of an affected child may wish to consider prenatal testing or preimplantation genetic diagnosis as risk may be greater than in the general population owing to the possibility of parental germline mosaicism (estimated empirically at <1%).

2372-0697
Reijnders, Margot R F
32103b31-0808-43b2-a5ee-eaf4229d587c
Leventer, Richard J
df0fcfe9-a398-4a5e-903b-332c4bb0aba7
Lee, Boo Hon
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Baralle, Diana
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Selber, Paulo
bfa7c7d7-53b3-4022-9276-a84995d194bd
Paciorkowski, Alex R
9e8a8293-c2d2-4506-bcd0-ec6630821e4a
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d
Reijnders, Margot R F
32103b31-0808-43b2-a5ee-eaf4229d587c
Leventer, Richard J
df0fcfe9-a398-4a5e-903b-332c4bb0aba7
Lee, Boo Hon
78920afd-9ff9-4790-8407-1511116cab0c
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Selber, Paulo
bfa7c7d7-53b3-4022-9276-a84995d194bd
Paciorkowski, Alex R
9e8a8293-c2d2-4506-bcd0-ec6630821e4a
Hunt, David
5867549e-0e44-4f07-9a42-93aaf092fd4d

Reijnders, Margot R F, Leventer, Richard J, Lee, Boo Hon, Baralle, Diana, Selber, Paulo, Paciorkowski, Alex R and Hunt, David (2017) PURA-related neurodevelopmental disorders. Gene Reviews.

Record type: Article

Abstract

Clinical characteristics. PURA-related neurodevelopmental disorders include PURA syndrome, caused by a heterozygous pathogenic sequence variant in PURA, and 5q31.3 deletion syndrome, caused by a genomic 5q31.3 deletion encompassing all or part of PURA. PURA-related neurodevelopmental disorders are characterized by moderate to severe neurodevelopmental delay with absence of speech in most and lack of independent ambulation in many. Early-onset problems can include hypotonia, hypothermia, hypersomnolence, feeding difficulties, excessive hiccups, recurrent central and obstructive apneas, epileptic seizures, abnormal non-epileptic movements (dystonia, dyskinesia, and dysconjugate eye movements), and abnormal vision. Congenital heart defects, urogenital malformations, skeletal abnormalities, and endocrine disorders occur, but are less common.

Diagnosis/testing. The diagnosis of a PURA-related neurodevelopmental disorder is established in a proband with either a heterozygous PURA pathogenic sequence variant (90% of affected individuals) or a non-recurrent deletion of 5q31.3 that encompasses all or part of PURA (10%).

Management. Treatment of manifestations: Ongoing routine care by a multidisciplinary team. Treatment and/or therapy for developmental delays; neurologic findings (hypotonia, seizures, abnormal movements); feeding difficulties; apnea; visual impairment; and malformations of the heart, urogenital tract, and skeleton.

Surveillance: Long-term follow up to assess psychomotor development, seizures or suspected seizures, vision, feeding for dysphagia, and musculoskeletal complications (hip dysplasia and scoliosis).

Genetic counseling. PURA-related neurodevelopmental disorders, caused by either a heterozygous PURA pathogenic sequence variant or a 5q31.3 deletion encompassing all or part of PURA are inherited in an autosomal dominant manner. In almost all probands with a PURA pathogenic sequence variant the sequence variant is de novo; to date, all reported 5q31.3 deletions have been de novo. For parents of an affected child, the risk to future pregnancies is presumed to be low, as a de novo genetic alteration involving PURA is most likely in the proband. However, parents of an affected child may wish to consider prenatal testing or preimplantation genetic diagnosis as risk may be greater than in the general population owing to the possibility of parental germline mosaicism (estimated empirically at <1%).

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PURAgenereviews2017 - Accepted Manuscript
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More information

Accepted/In Press date: 24 April 2017
Published date: 27 April 2017
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 408118
URI: http://eprints.soton.ac.uk/id/eprint/408118
ISSN: 2372-0697
PURE UUID: 6b4cdbad-acf0-44dd-9007-79190b4f6830
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 12 May 2017 04:03
Last modified: 16 Mar 2024 03:57

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Contributors

Author: Margot R F Reijnders
Author: Richard J Leventer
Author: Boo Hon Lee
Author: Diana Baralle ORCID iD
Author: Paulo Selber
Author: Alex R Paciorkowski
Author: David Hunt

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