Glass Syndrome

Glass syndrome is a contiguous gene deletion disorder due to a deletion at 2q32.2q33.1 that includes SATB2, with intellectual disability, severe speech impairment, cleft palate, micrognathia and dental anomalies. It is the larger deletion counterpart of SATB2-associated syndrome, and the extra genes in the interval can add features.

Pathophysiology. SATB2 is a chromatin organising transcription factor needed for cortical neuron identity, osteoblast differentiation and craniofacial development. Loss of one copy explains the core phenotype. Other genes in the deleted interval may add to growth, skeletal and neurodevelopmental findings.

Deletions are usually de novo, and sizes vary between patients.

Array testing is the first step in diagnosis.

• Moderate to severe intellectual disability and severe speech delay
• Cleft palate, high arched palate, and micrognathia (Pierre Robin sequence in infancy)
• Dental abnormalities: crowding, abnormal roots, and abnormal eruption
• Feeding difficulty in infancy
• Behavioural problems: aggression, hyperactivity and autism features
• Sleep disturbance
• Low bone mineral density and fractures in some
• Short stature or small head size in some
• Hearing loss and recurrent otitis media
• Skeletal findings such as scoliosis in some
• Features that differ from SATB2-associated syndrome alone may relate to the size of the deletion

• Chromosomal microarray: the first test, to identify and size a 2q32.2q33.1 deletion and to list the genes included.
• SATB2 sequencing when the array is normal and the phenotype fits.
• Parental testing to confirm de novo origin.
• Craniofacial and palate assessment, and dental review with radiographs.
• Hearing assessment.
• Developmental assessment, with bone density scan if there are fractures.

Differential diagnosis.

• SATB2-associated syndrome from an intragenic variant
• Other 2q deletion syndromes
• Pierre Robin sequence from other causes (Stickler syndrome, 22q11.2 deletion)
• Pitt-Hopkins syndrome

• Cleft palate and airway: surgical repair at 6 to 12 months by a cleft team, with positioning and nasopharyngeal airway or mandibular distraction for severe obstruction.
• Feeding: specialised bottles or tube feeding, and gastrostomy if unsafe swallow persists.
• Speech and communication: early speech therapy with augmentative communication, because spoken language is often very limited.
• Dental care: dental review from 1 year, early orthodontic planning, and care under general anaesthesia when needed.
• Hearing: grommets for persistent otitis media with effusion, and hearing aids for hearing loss.
• Bone health: vitamin D 400 to 800 international units daily in children (1000 to 2000 international units in adults), calcium by diet, and assessment of fractures. Consider bisphosphonate treatment only under specialist care.
• Behaviour and sleep: behavioural support, melatonin 2 to 5 mg 30 to 60 minutes before bed (up to 10 mg if needed), and risperidone 0.25 mg daily increasing to 1 to 2 mg daily for severe irritability, with metabolic monitoring.
• Genetic counselling: de novo deletions carry low recurrence risk, unless a parent has a balanced rearrangement.

Special groups.

• Infants with micrognathia: monitor oxygen saturations during sleep and feeds.

Monitoring. Growth, feeding and airway in infancy at each visit. Speech and development every 6 months, dental review every 6 months, and hearing yearly.

Referral and escalation. Refer to clinical genetics, a cleft and craniofacial team and speech therapy. Emergency for airway obstruction or aspiration.