White-Sutton Syndrome

White-Sutton syndrome is an autosomal dominant neurodevelopmental disorder caused by loss-of-function variants in POGZ (1q21.3), with intellectual disability, autism spectrum disorder, microcephaly and characteristic features. Variants are usually de novo.

Pathophysiology. POGZ is a zinc finger protein that interacts with heterochromatin protein 1 and regulates chromatin and mitosis. Haploinsufficiency disrupts neurogenesis and synaptic function.

Phenotype varies widely, from mild learning problems to severe intellectual disability.

Vision, hearing and gut problems are frequent and treatable.

• Developmental delay, intellectual disability (mild to severe), speech delay
• Autism spectrum disorder, ADHD, self-injury, sleep disturbance
• Microcephaly, short stature, hypotonia
• Visual problems: refractive error, strabismus, cortical visual impairment
• Sensorineural or conductive hearing loss
• Feeding problems, constipation, reflux
• Seizures in a minority
• Congenital heart disease, genitourinary anomalies
• Pain insensitivity or high pain threshold reported
• Mild dysmorphism: broad forehead, wide set eyes, thin upper lip

• POGZ sequencing with deletion and duplication analysis, or exome or genome sequencing; chromosomal microarray for 1q21.3 deletions.
• Developmental and behavioural assessment including autism evaluation.
• Ophthalmology and audiology assessment.
• Echocardiography and renal ultrasound.
• EEG and brain MRI if seizures or regression.
• Parental testing to confirm de novo origin.

• Development and communication: early intervention, speech and language therapy, augmentative communication, occupational therapy and special education.
• Vision and hearing: spectacles, treatment of strabismus (patching or surgery), and hearing aids or grommets.
• Behaviour and ADHD: structured behavioural programmes, and methylphenidate 5 mg orally once or twice daily increasing weekly by 5 to 10 mg to a usual maximum of 60 mg daily after cardiac review.
• Anxiety and mood: sertraline 25 to 50 mg daily increasing to a maximum of 200 mg daily when needed.
• Sleep: sleep hygiene and melatonin 2 to 5 mg orally 30 to 60 minutes before bed (up to 10 mg if needed).
• Feeding and gastrointestinal care: feeding therapy, gastrostomy if unsafe, macrogol 0.4 to 0.8 g/kg daily (adults 1 to 3 sachets) for constipation, and omeprazole 0.7 to 1 mg/kg daily for reflux.
• Seizures: levetiracetam 10 mg/kg twice daily increasing to 30 mg/kg twice daily.
• Safety: watch for unrecognised injury because of high pain threshold.
• Genetic counselling: de novo variants carry low recurrence risk (germline mosaicism is rare).

Special groups.

• Adolescents and adults: continue behavioural and mental health care, and plan transition to adult services.

Monitoring. Development and behaviour every 6 to 12 months. Vision and hearing yearly, growth and head circumference at each visit, and echocardiography once.

Referral and escalation. Refer to clinical genetics, developmental paediatrics and ophthalmology. Urgent for seizures, regression or self-injury.