Clinical Guidance

Current data suggest that PURA variants in the region encoding the PUR III repeat cause a more severe phenotype than variants in the regions that encode PUR I or PUR II repeats (see , Normal gene product). However, the functional effect at a molecular level is not yet clear and requires further investigation . PURA-related neurodevelopmental disorders encompass both PURA syndrome and the 5q31.3 deletion syndrome. It has been suggested that PURA haploinsufficiency contributes to the neurodevelopmental phenotype of individuals with a 5q31.3 deletion . The features of individuals with a 5q31.

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"

Penetrance

To the authors' knowledge, the penetrance of all intragenic PURA pathogenic variants and 5q31.3 deletions encompassing PURA is complete.

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"

Diagnostic Criteria

No formal clinical diagnostic criteria have been published for PURA-related neurodevelopmental disorders, which comprise PURA syndrome (caused by a heterozygous PURA pathogenic sequence variant) and 5q31.3 deletion syndrome (caused by a nonrecurrent 5q31.3 deletion encompassing all or part of PURA).

Suggestive Findings

A PURA-related neurodevelopmental disorder should be suspected in infants and older individuals with the following clinical findings.

Infants

• Hypotonia

• Neonatal hypoventilation

• Hypothermia

• Hypersomnolence

• Feeding difficulties, including gastroesophageal reflux disease (GERD)

Older individuals

• Hypotonia

• Moderate-to-severe intellectual disability, including absent speech

• Seizures

• Abnormal nonepileptic movements (e.g., dystonia, dyskinesia, and dysconjugate eye movements)

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"

Differential Diagnosis

Disorders in the differential diagnosis of PURA-related neurodevelopmental disorders are:

• Congenital central hypoventilation syndrome

• Prader-Willi syndrome

• Lower extremity-predominant autosomal dominant spinal muscular atrophy 1 (OMIM 158600)/ distal autosomal recessive spinal muscular atrophy 1 (OMIM 604320)

• Myotonic dystrophy in the newborn (see Myotonic Dystrophy Type 1)

• Neurotransmitter disorder

• Rett syndrome

• Pitt-Hopkins syndrome

• Angelman syndrome

See Mental retardation, autosomal dominant: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with a PURA-related neurodevelopmental disorder, the following evaluations are recommended.

Table 2.

Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Cognitive

| Developmental assessment |

Neurologic

| Neurologic eval |

Brain MRI | Indicated in a child w/a PURA-related neurodevelopmental disorder w/seizures /or hypoventilation /or abnormal vision or eye movements who has not previously had a brain MRI

EEG video EEG | If seizures are suspected

Eyes | Ophthalmology exam | Electrodiagnostic tests may be indicated.

Cardiovascular

| Consider echocardiogram |

Respiratory

| Assessment of pulmonary function | As needed

Gastrointestinal

|

• Feeding assessment w/analysis of swallowing eval for possible aspiration

• Assessment for constipation

| As needed

Genitourinary

| Consider ultrasound of the urinary tract. |

Musculoskeletal

| Appropriate radiographs | If hip dysplasia /or scoliosis is suspected

Endocrine

| Assessment of serum vitamin D levels |

Assessment of bone density | If osteoporosis or osteopenia is suspected

Eval of anterior pituitary hormones | If necessary

Miscellaneous/

Other

| Consultation w/clinical geneticist /or genetic counselor |

Treatment of Manifestations

Individuals often benefit when management is provided by a multidisciplinary team including relevant specialists, which may include, but is not limited to, a pediatrician, clinical geneticist, chi...

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"

Surveillance Guidelines

Table 4. Recommended Surveillance for Individuals with PURA-Related Neurodevelopmental Disorders

Source: GeneReviews — "PURA-Related Neurodevelopmental Disorders"