Table 4 Proposal for a minimal dataset for clinical evaluation, management, and follow-up on Malan syndrome
Intervention | Evaluation | Frequency and follow-up |
|---|---|---|
Auxological evaluation | Evaluate habitus, measurement of weight, length/height, head circumference | Complete evaluation with measurement of weight, length/height, head circumference at diagnosis. Repeat auxological evaluation every six months during the first 2 years of life, then at least annually |
Calculate BMI-SDS and calories intake, reassure about appropriateness in food intake. Variate diet. If < 2SDS evaluate calories intake | Refer to pediatrician for BMI-SDS surveillance (first evaluation after 2 years of age) | |
Orthopedic evaluation | Evaluate spine curvature, body length discrepancies, flat feet. When required involve specialized practitioners (e.g., orthopedic surgeon, physiatrist, physiotherapist). Perform skeletal Xray if needed | At diagnosis, then evaluate annually until puberty |
Accurate anamnesis for bone fractures. Consider DXA | DXA should be performed during puberty or earlier if presence of pathologic fractures | |
Ophthalmologic evaluation | Perform Ophthalmologic/Orthoptic evaluation. Search for refractive errors, nystagmus, strabismus, polar cataract, and optic disk pallor. Consider VEP and ERG to assess conduction in visual pathway | At diagnosis, then annually until puberty |
Neurological evaluation I.CNS anomalies | MRI at diagnosis with critical search for CCH, wide ventricles, brain atrophy and CM1. Consider specific evaluation of optic nerve at MRI to detect Optic Nerve hypoplasia | At diagnosis. If CM1 is detected at MRI perform imaging follow-up. If CM1 is associated to syringomyelia consider neurosurgeon evaluation for proper timing of the imaging |
II.Neurovegetative symptoms | Symptoms may be subtle or aspecific (e.g., vomiting/nausea, dizziness fainting). Look for CM1 and consider neurologic evaluation. Exclude other causes (e.g., cardiologic/otolaryngology evaluation) | At diagnosis, evaluate possible appropriate drug therapy, subsequent follow up |
III.Epilepsy and EEG anomalies | Perform EEG in asymptomatic patients, educate caregivers to promptly recognize subtle symptoms | At diagnosis. If EEG aspecific anomalies alone are detected: watch and wait strategy, especially in NFIX SV. In patients with NFIX microdeletions consider closer follow-up due to the higher risk in developing seizures |
If onset of seizures: Perform neurological evaluation and EEG, if required start antiepileptic therapy | At diagnosis, then on neurological indication | |
Neuropsychiatric and Behavior evaluation | Perform neuropsychiatric and behavior evaluation Verify visuomotor abilities, noise sensitivity and photophobia. Suggest symptomatic aids (i.e., coloured glasses, recommend low voice tone) when appropriate to reduce anxiety outbursts | At diagnosis, then on neuropsychiatric indication |
Orodental Odontoiatric evaluation | Evaluate ogival palate, tooth overgrowth, malocclusions, caries. Educate to proper dental care | At diagnosis, then annually or on specific indications |
Gastrointestinal evaluation | Look for constipation and treat it. Perform abdominal ultrasound to look for hepatomegaly and/or kidney enlargement | At diagnosis. Refer to pediatrician for possible therapy of constipation |
Neoplasm surveillance | No consistent evidence for strict neoplasm surveillance | None |
Cardiological evaluation | Perform echocardiogram. Look for AD, MR, other CHD | At diagnosis. Refer to pediatrician for periodic clinical evaluation |
Genetic counselling | Appropriate genomic/genetic testing to exclude parental mosaicism. Consider parental or gonadal mosaicism | At diagnosis. Prenatal counselling in families with a known MALNS offspring conceived by ART |