A Customized Next-Generation Sequencing-Based Panel to Identify Novel Genetic Variants in Dementing Disorders: A Pilot Study

Table 1

Patients’ clinical-demographic data and main laboratory-instrumental findings.

Patient’s number	1	2	3	4	5	6	7	8
Sex	M	M	F	F	F	M	F	M
Age	35	34	69	59	71	66	87	85
Parents’ consanguinity	—	+	+	—	—	—	—	—
Family history	—	+ (brother)	—	+ (mother, brother)	+ (father, sister)	+ (not specified)	—	—
Age at onset	34	32	66	54	66	65	82	84
Past medical history	Unremarkable	Traumatic brain injury at 1-year old; smoking and cannabis abuse	Hypothyroidism dyslipidemia; lumbar disc protrusions and spondylosis	Mild hypothyroidism	Hypertension; dyslipidemia	Peripheral L facial nerve palsy; R-side sphenoidal meningioma	Diabetes; chronic ischemic heart disease	Duodenal ulcer; benign prostatic hyperplasia
Clinical presentation	Urge incontinence; behavioral changes (irritability, apathy); gait and speech slowness	Behavioral changes (verbal aggressivity, personal carelessness); speech and memory deficit; disorientation; postural instability with some falls	Motor slowness; L hand tremor; progressive memory deficit; depressed mood; episodes of falls; insomnia with excessive daytime sleepiness	Behavioral changes; obsessive thoughts; delirium and complex visual hallucinations (> mysticism); dysphagia; episodes of loss of consciousness; incontinence	Progressive memory deficit and disorientation; slight behavioral changes (apathy, irritability); lack of insight	Progressive speech disorder, with anomia and deficit of object naming; irritability	Progressive memory deficit; loss of personal independence	Progressive memory deficit and disorientation; loss of personal independence; episodes of falls without loss of consciousness; mild bilateral kinetic tremor of the hands
Clinical signs	Hypomimic face; gait and speech slowness; R>L hand postural tremor; L>R upper limb bradykinesia and plastic hypertonus; diffuse brisk tendon reflexes; bilateral Babinski sign; frontal release signs	Gait disorder; mild cerebellar signs; L-beating nystagmus; bilateral palmomental reflex	Hypomimic face; bradykinesia; parkinsonian gait; head and voice tremor; postural instability; L>R upper limb postural and kinetic tremor; L Hoffman sign; bilateral palmomental reflex	Hypomimic face, drooling; akathisia; dysarthria; dysphagia; mandibular contracture; diffuse plastic hypertonus and bradykinesia; bilateral palmomental reflex	Diffuse brisk tendon reflexes; L Hoffman sign; bilateral palmomental reflex	L facial nerve palsy; bilateral sensory-neural hearing loss; anomia, semantic paraphasia	Frontal release signs; diffuse hypoexcitable tendon reflexes	Limping gait; inconstant R hand tremor; diffuse brisk tendon reflexes; positive frontal release signs
ADL; IADL	6/6; 8/8	4/6; 5/8	5/6; 3/8	2/6; 0/8	6/6; 8/8	6/6; 8/8	4/6; 0/8	3/6; 0/8
Neuropsychologic evaluation	Moderate major neurocognitive disorder	Severe major neurocognitive disorder with behavioral changes	Mild neurocognitive disorder	Severe major neurocognitive disorder with behavioral changes	Mild neurocognitive disorder	Mild neurocognitive disorder	Severe major neurocognitive disorder	Severe major neurocognitive disorder
Extensive laboratory exams	Normal	Folate: 7.0 nmol/l (n.v. 10.4-42.4); homocysteine: 37.6 μmol/l (n.v. 3.6-15.0)	Thyroid stimulating hormone: 6.8 mcrUI/ml (n.v. 0.3-4.2)	Erythrocyte sedimentation rate: 50 mm/h (n.v. 2-12)	Low-density lipoprotein: 165 mg/dl (n.v. 0-100)	Prostate specific antigen: 9.2 ng/ml (n.v. 1.0-5.4)	Glycated hemoglobin: 6.1% ()	Hemoglobin 10.7 g/dl (n.v. 13.0-17.5); free thyroxine 28.1 pg/ml (n.v. 9.3-17.0)
EEG	Normal	Low-amplitude alpha rhythm; sporadic muscular activations, not correlated with EEG changes	Normal	Normal	Normal	Sporadic slow activity over the frontal and temporal regions	Diffuse slow activity	Diffuse slow activity
Brain MRI	Diffuse cortical and subcortical atrophy (>midbrain, and corpus callosum); ischemic WMLs (> periventricular and frontal regions)	Diffuse cortical and subcortical atrophy (>frontal and temporal lobes, corpus callosum); multiple ischemic WMLs (> periventricular)	Diffuse cortical atrophy; chronic vascular lesion of periventricular frontal regions; mild ischemic WMLs	Diffuse cortical and subcortical atrophy (>frontal and perisylvian regions); mild ischemic WMLs	Moderate cortical atrophy (>frontal and temporal regions); mild ischemic WMLs	R-side parasellar meningioma; moderate diffuse cortical atrophy; mild ischemic WMLs	Diffuse cortical and subcortical atrophy	Diffuse cortical and subcortical atrophy
Other exams	EMG: normal.; Multimodal EPs: normal.; CSF: total tau: 266 pg/ml (n.v. ).; Perfusional SPECT: bilateral frontal, parietal, and temporal hypoperfusion.; DAT-scan SPECT: L>R nigrostriatal denervation	EMG: normal.; Multimodal EPs: normal.; CSF analysis: normal	Unremarkable	EMG: diffuse neurogenic changes (>bilateral deltoid and right biceps brachii muscles); no cranial muscle denervation.; Spine MRI: disc protrusion C5-C6, L4-L5, and L5-S1; spondylosis	Transthoracic echocardiogram: L ventricle enlargement	Supra-aortic vessels ultrasound: bilateral carotid artery thickening	Chest X-ray: signs of chronic obstructive pulmonary disease.; Transthoracic echocardiogram: L ventricle hypertrophy and moderate mitral valve insufficiency	Chest X-ray: signs of chronic obstructive pulmonary disease.; Transthoracic echocardiogram: L ventricle enlargement
Diagnosis at discharge	PD-dementia	FTD	PD-dementia	FTD	MCI	MCI	AD	AD

Legend (in alphabetic order): -=absent/negative; +=present/positive; AD=Alzheimer’s disease; ADL=activity of daily living; CSF=cerebrospinal fluid; DAT=dopamine transporter; EEG=electroencephalogram; EPs=evoked potentials; FTD=frontotemporal dementia; F=female; IADL=instrumental activity of daily living; L=left; M=male; MCI=mild cognitive impairment; MRI=magnetic resonance imaging; n.v.=normal values; PD=Parkinson’s disease; R=right; SPECT=single-photon emission computed tomography; WMLs=white matter lesions.