Table 1

Demographic and clinical features of sequenced patients

TrioSexAgeRaceSymptomsGenetic tests performed clinically before enrolment in study
1M8IndianDevelopmental delay, possible autism, microcephaly, dysmorphic features, spine abnormalities, sensorineural hearing lossChromosome microarray (paternally inherited 15q13.3 dup), Fragile X
2M3European-AmericanDevelopmental delay, multifocal epilepsy, involuntary movements, abnormal liver function, absent tearsChromosomes, chromosome microarray, Niemann-Pick type C, hepatocerebral mDNA depletion panel (POLG1, DGUOK, MPV17), ataxia with oculomotor apraxia type 2 (SETX), Allgrove Syndrome, ataxia telangectasia (ATM), Rett (MECP2), alpha—1 antitrypsin (AAT), congenital disorder of glycosylation (transferrin isoelectric focusing and N-glycan analysis), metabolic tests (Tay Sachs, Sandhoff, mannosidosis, mucolipidosis II, Krabbe, metachromatic leukodystrophy, adrenoleukodystrophy, GAMT, plasma amino acids, plasma acylcarnitine, urine organic acids).
3M3European-AmericanDevelopmental delay, autism, coarctation of the aorta, tethered cord, congenital nystagmus and strabismusChromosome microarray (maternally inherited 15q26.3 deletion), Smith-Lemli-Opitz, Aarskog
4FadultEuropean-Americanmultiple congenital abnormalities and macular degenerationChromosome microarray (2 stretches of loss of heterozygosity on chromosome 2), Fragile X (premutation carrier)
5F12European-AmericanSevere intellectual disability, autism, bilateral hyperpronated feet, facial dysmorphismsChromosomes, chromosome microarray, Rett, Angelman methlyation, Fragile X, Cohen Syndrome
6M18European-AmericanIntellectual disability, epilepsy, panhypopituitarism, hypertension, bifid great toe, vertebral segmentation anomalies and sagittal cleft of the vertebra, hypoplastic 13th rib, and delayed bone ageChromosomes, chromosome microarray, Borgeson-Forssman-Lehman syndrome
7M2European-AmericanMicrocephaly, facial asymmetry, acyanotic Tetralogy of Fallot; history of small muscular ventricular septal defect; right aortic arch with mirror image branching; malformed right ear with hearing loss, bifid uvula, cleft soft palateChromosome microarray, CHARGE (CHD7)
8M16European-AmericanSevere intellectual disability, dysmorphic features evident, bicuspid aortic valve, bilateral coronal craniosynostoses,quadriplegic cerebral palsy, bilateral inguinal hernias, G-tube placement and obstructive sleep apnoeaChromosome microarray, craniosynostosis syndromes (FGFR2), non-syndromic craniosynostosis (FGFR3) Saethre-Chotzen syndrome (TWIST)
9F4AlgerianDevelopmental delay, bilateral congenital cataracts and strabismus, ventricular and atrial septal defects, a unilateral clubfoot, and unilateral choanal atresiaChromosome microarray (Long stretch of loss of heterozygosity on chromosome 17), CHARGE (CHD7), PAX6, 7-dehydrocholesterol and cholesterol levels
10M11European-AmericanAttention deficit hyperactivity disorder, language delays, coarse facial features, bilateral mandibular cysts, low muscle toneChromosome microarray, Costello (H-RAS), Gorlin (PTCH), Comprehensive Noonan sequencing array (BRAF, HRAS, KRAS MAPT2K1, MAPTK2, PTPN11, RAF1, SHOC2 and SOS1), MPS panel
11M9European-AmericanSevere intellectual disability, developmental delay, seizures/infantile spasms, hypotonia and minor dysmorphismsChromosomes, chromosome microarray (familial Xp11.4 duplication), acylcarnitine profile, plasma amino acids, urine organic acids, creatine/guanidinoacetate analysis in urine and blood
12F4European-AmericanSpeech delay, borderline microcephaly, failure to thrive, dysplastic nails, ventricular septal defect and hip dysplasiaChromosomes, chromosome microarray