Clinical Guidance
Shashi-Pena syndrome is characterized by distinctive facial features accompanied by variable further clinical findings, which may include macrocephaly, dental anomalies, congenital heart defects, seizures, hypoglycemia, hypotonia, developmental delays/ intellectual disabilities, skeletal abnormalities, and global volume loss on brain MRI. To date, at least 23 individuals have been identified with pathogenic truncating variants in ASXL2, including published and non-published individuals [; ; ; ; ; ; JM Porter, LDM Pena, RC Spillmann, A Johnson, V Shashi, unpublished data]. The following description of the phenotypic features associated with this condition is based on these individuals. Table 2. Shashi-Pena Syndrome: Frequency of Select Features1,2
Feature | Number of Persons w/Feature | Comment |
|---|
Glabellar nevus simplex | 23/23 (100%) | — |
Distinctive facial features | 22/22 (100%) | See . |
Dental abnormalities | 14/14 (100%) | Early eruption loss; small, fragile teeth |
Developmental delay/intellectual disability | 20/21 (95%) | Variable, ranging from low-average intellectual abilities to severe intellectual disabilities |
Hypotonia | 19/20 (95%) | Gradual improvement w/age; likely to be central |
Other skin findings | 17/20 (85%) | Capillary malformations (11/20), deep palmar creases (6/20), hypertrichosis (4/20) |
Feeding difficulties (newborn) | 17/20 (85%) | May require nasogastric/gastrostomy tube feeding, but usually resolve over time |
Feeding difficulties (childhood) | 5/18 (28%) | — |
Skeletal anomalies | 14/17 (82%) | May incl scoliosis/kyphosis, hypermobility, /or frequent fractures |
Congenital heart defects | 17/21 (81%) | ASD, PFO, PDA |
Macrocephaly | 15/20 (75%) | Congenital acquired both reported |
Vision abnormalities | 11/15 (73%) | Strabismus, amblyopia; ptosis is part of the distinctive facial features |
Behavior problems | 10/14 (71%) | Aggression, anger outbursts |
Seizures | 12/18 (67%) | Febrile /or non-febrile |
Hypoglycemia | 13/20 (65%) | Most often in neonates may be due to hyperinsulinism; frequently resolves over time |
Macrosomia | 10/18 (55%) | — |
Hearing loss | 7/15 (47%) | Typically conductive |
Sleep apnea | 7/15 (47%) | May be obstructive or mixed central/obstructive |
Temperature dysregulation | 6/14 (43%) | ASD = atrial septal defect; PFO = patent foramen ovale; PDA = patent ductus arteriosus Data is derived from 12 published individuals and 11 unpublished individuals [; ; ; ; ; ; JM Porter, LDM Pena, RC Spillmann, A Johnson, V Shashi, unpublished data]. 2. Skin. |
Source: GeneReviews — "Shashi-Pena Syndrome"
