Table 1.
Surveillance and Management Consensus Guidelines for Neurodevelopmental Features in Patients With PHTS (Based on the Second Stage of the Modified Delphi Process)
| Statement | Clinical recommendation | Evidence grade and agreement, (%) | Key details |
| Initial diagnosis and patient education | |||
| N1/ND1 | Educate patients/caregivers at diagnosis on potential neurodevelopmental/neuropsychiatric complications | Weak (100) | Complications to discuss: autism, mood/behavioral issues, sleep problems, IDD, learning differences, ADHD Less common: Seizures, Lhermitte-Duclos disease, vasculopathy |
| Routine monitoring and screening | |||
| ND3 | Routinely measure head circumference (occipitofrontal) up to age 5 y | Weak (83) | At least annually |
| ND4 | Conduct developmental evaluation for young children at diagnosis; monitor ongoing if indicated | Strong (83) | Identify issues and guide accommodations/interventions |
| ND5 | Conduct comprehensive neuropsychological assessment at diagnosis | Strong (83) | Regardless of age, proactively identify issues and guide accommodations/interventions |
| ND8 | Assess fine and gross motor skills via formal neurologic examination at diagnosis (all ages) | Strong (83) | Regardless of age, at least by school age for early diagnoses. Can be part of developmental/neuropsychological assessment |
| ND9 | Assess sensory features | Strong (83) | Regardless of age; at least by school age for early diagnoses |
| ND10 | Offer assessment of psychological and behavioral functioning (all ages) | Strong (83) | At diagnosis, or at least by school age for early diagnoses, as clinically indicated |
| ND11 | Routinely screen for depression and anxiety symptoms | Weak (80) | Start as early as age 6 y (if indicated), at least by age 12 y. Screen at least annually, or more frequently |
| ND16 | Screen for and counsel about potential sleep issues | Expert opinion (67) | Includes insomnia, frequent arousals, RLS, reduced restful sleep, anxiety-related sleep disorders, OSA, and other sleep challenges |
| Targeted interventions and management | |||
| ND2 | Avoid routine mTOR inhibitors for neuropsychiatric/neurocognitive symptoms outside of clinical trials | Strong (100) | Use only if deemed clinically appropriate by the treating clinician |
| ND6 | Implement appropriate behavioral interventions for diagnosed ASD or significant autism symptoms | Strong (100) | Focus on improving social interaction, communication, and adaptive functioning |
| ND7 | Promptly conduct hearing and comprehensive speech-language evaluation for expressive/receptive language delays (e.g., nonspeaking and minimally verbal) | Strong (100) | By 3.5 y of age, identify specific issues and guide accommodations/interventions |
| ND12 | Refer individuals with psychological/behavioral difficulties to a licensed professional | Strong (100) | For treatment (behavioral support, psychotherapy, pharmacotherapy) or psychiatric evaluation, as indicated |
| ND13 | Use sleep hygiene and behavioral sleep medicine techniques as first-line treatment for insomnia | Strong (100) | |
| ND14 | Evaluate for OSA if headache/excessive daytime sleepiness OR if STOP-BANG criteria met. | Strong (83) | STOP-BANG criteria: ≥2 of snoring, tiredness, observed apnea, high BP. BMI >35, age >50 y, neck circumference >40 cm, male sex. If confirmed, treat with CPAP/other interventions via sleep specialist |
| ND15 | Follow relevant practice guidelines for sleep disorders in PHTS and autism spectrum disorder | Weak (100) | |
| ND17 | Minimize sedative/hypnotic medications (e.g., zolpidem) for sleep disturbances | Expert opinion (100) | Lack of scientific evidence for routine use in PHTS |
| ND18 | For established RLS, check serum ferritin levels | Expert opinion (83) | If ferritin <50−75 μg/L, trial oral iron supplementation (2–3 mo) before drug therapy |
Abbreviations: ADHD = attention deficit hyperactivity disorder; ASD = autism spectrum disorder; BMI = body mass index; BP = blood pressure; CPAP = continuous positive airway pressure; IDD = intellectual developmental disorder; ND = neurodevelopmental; OSA = obstructive sleep apnea; PHTS = PTEN hamartoma tumor syndrome.