ASXL3/Bainbridge-Ropers Syndrome; ASXL3 Syndrome BRPS; ASXL3 Syndrome; ASXL3-Related Disorder; Severe Feeding Difficulties Failure to Thrive Microcephaly Due to ASXL3 Deficiency Syndrome

Bainbridge-Ropers syndrome (BRPS) is a neurodevelopmental disorder caused by mutations in the ASXL3 gene. It is characterized by delayed psychomotor development, intellectual disability, absent or poor speech, hypotonia, poor growth, seizures, and dysmorphic facial features. Affected individuals may also display autistic features. Some individuals may have issues with feeding and cyclic vomiting during infancy. While dysmorphic facial features have been described, they are typically nonspecific. Affected individuals may also have hypotonia that can transition to spasticity resulting in unusual posture with flexion contractions of the elbows, wrists, and fingers. Other findings may include strabismus, sleep disturbance, and palate and dental anomalies.

Diagnostic testing: The diagnosis of BRPS is made by:

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  Symptoms;

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  Clinical examination;

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  Chromosomal microarray analysis; and

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  Genetic testing for mutation of the ASXL3 gene.

Physical findings:The frequently occurring physical signs and symptoms of BRPS include:

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  Feeding difficulties in infancy;

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  Global developmental delays;

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  Infantile muscular hypotonia (decreased muscle tone);

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  Intellectual disability, which may be severe or profound;

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  Neurological speech impairment;

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  Abnormality of the skeletal system;

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  Absent speech;

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  Autistic behavior;

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  High, narrow palate;

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  Loose joints and wrists that bend inward;

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  Microcephaly (abnormally small head); and

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  Strabismus (misalignment of the eyes).

ICD-9: 755.55; 758.9

ICD-10: Q87.0

Symptoms of BRPS may start to appear during pregnancy, at birth, and as an infant. Most affected individuals display normal birth weight for gestational age but often experience poor postnatal growth because of feeding issues during infancy. They may display poor suck and swallow, recurrent vomiting, and GERD (gastroesophageal reflux disease). Most individuals with ASXL3 -related disorder, especially in the younger age groups, come to medical attention because of poor postnatal growth and ongoing feeding difficulties. Growth and height typically stabilize or normalize after appropriate treatment of feeding issues.

Hypotonia is a common feature in individuals with ASXL3-related disorder, especially during the neonatal period and in early infancy. Later in life, some children develop an unusual posture and contractures with elbow, wrist, and fingers held in the flexion position. This is likely because of spasticity that becomes apparent with age.

Seizures occur in about one third of affected individuals and can range from generalized tonic-clonic seizures to absence seizures. Seizures typically respond to standard anti-seizure medications.

Most individuals with ASXL3-related disorder have normal brain imaging and do not have any characteristic brain findings.

There is no curative treatment for this syndrome. Complications are typically managed through a multidisciplinary team of medical specialists and therapists (speech therapy, physical therapy, occupational therapy, etc.).

Treatment is symptom specific and supportive and may include feeding therapy; gastrostomy tube placement for those with persistent feeding issues; anti-reflux medication or fundoplication for those with gastroesophageal disease; standard treatment for epilepsy, joint contractures, sleep apnea, dental anomalies, strabismus or refractive error, and developmental delay/intellectual disability.

Suggested MER for Evaluation:

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  Clinical history and examination that describes diagnostic features of the impairment; and

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  Genetic sequencing tests confirming mutation of the ASXL3 gene.

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