| | Study ID | Submitted clinical presentation | Prior genetic testing | Molecular mechanism | Dx/related features | Overlapping/distinctive |
| | PKIG00165 [7] | 9-month-old male with severe growth and developmental delay, failure to thrive, Romano-Ward syndrome, hx of G-tube feeding, metabolic disorder, mitochondrial metabolic disorder, agenesis of corpus callosum, seizure disorder, hypertension, irregular breathing pattern, hypoxia, lactic acidosis, acute respiratory failure with hypoxia and hypercapnia, respiratory distress, respiratory insufficiency, half-sibling with autism | External WES: KCNH2 variant and SLC25A19 variants reported | KCNH2 c.774_789del p.?, heterozygous, pathogenic | Long QT syndrome 2; short QT syndrome 1/Romano-Ward syndrome | Distinctive | | SLC25A19 c.115A>T p.(Ile39Phe), heterozygous, VUS | Microcephaly, Amish type; thiamine metabolism dysfunction syndrome 4/severe growth and developmental delay, lactic acidosis | | SLC25A19 c.433C>A p.(Arg145Ser), heterozygous, VUS |
| | PKIG00217 | 8-year-old-female with mixed conductive and sensorineural hearing loss, short stature, bilateral hypermetropia, bilateral 5th finger brachydactyly, bilateral little finger clinodactyly, hoarseness. Clinical features manifested at 6 months | External panel testing: MYO3A VUS reported | ANKRD11 c.2288_2289del p.?, heterozygous, pathogenic | KBG syndrome/short stature, bilateral 5th finger brachydactyly, bilateral little finger clinodactyly | Distinctive | | TNC c.5692G>A p.(Val1898Ile), heterozygous, VUS | Deafness 56/hearing loss |
| | PKIG00252 | 14-year-old male with small pituitary gland, delayed motor development, delayed language development, nonverbal, profound intellectual disability, chorea, congenital muscular hypotonia, focal seizure, chronic encephalopathy, esotropia, inguinal hernia, self-injurious behavior. Clinical features manifested around 5 months | External karyotype, aCGH, myotonic dystrophy testing, Angelman/Prader-Willi syndrome methylation analysis, fragile X testing: nondiagnostic | CACNA1A c.2042_2043del p.?, heterozygous, pathogenic | Early infantile epileptic encephalopathy 42; episodic ataxia, type 2; familial hemiplegic migraine 1; spinocerebellar ataxia 6/delayed motor development, delayed language development, profound intellectual disability, chorea, hypotonia, seizure, encephalopathy | Overlapping features: delayed motor development, delayed language development, profound intellectual disability, hypotonia, seizure, encephalopathy | | GABBR2 c.1724C>A p.(Thr575Asn), heterozygous, VUS | Early infantile epileptic encephalopathy 59; neurodevelopmental disorder with poor language and loss of hand skills/delayed motor development, delayed language development, nonverbal, profound intellectual disability, hypotonia, seizure, encephalopathy, self-injurious behavior |
| | PKIG00301 | 7-year-old female with delayed motor development, delayed language development, intellectual disability, ataxia, muscular hypotonia, microcephaly, blepharospasm, ptosis, visual impairment, external ear malformation, postaxial polydactyly in hands, constipation, failure to thrive, short stature, congenital malformation of face and neck, aphasia. Clinical features manifested at 2 months | External karyotype: 3p25.3p26.1 deletion and 12p13.31 deletion of unknown significance reported | 1.9 Mb del of 3p26.1p25.2, heterozygous, pathogenic | 3p- syndrome/delayed motor development, delayed language development, intellectual disability, microcephaly, ptosis, hypotonia, postaxial polydactyly | Overlapping feature: delayed motor development, delayed language development, intellectual disability, microcephaly, hypotonia | | GRIN2B c.1427A>G p.(Tyr476Cys), heterozygous, VUS | Developmental and epileptic encephalopathy 27; intellectual developmental disorder 6 with or without seizures/delayed motor development, delayed language development, intellectual disability, microcephaly, hypotonia |
| | PKIG00439 | 18-year-old male with immunodeficiency, schizophrenia, dystonia, stroke like symptoms, ADHD, developmental delay, developmental regression, intellectual disability, ataxia, muscular hypotonia, encephalopathy, headache/migraine, abnormal creatine kinase, hyperalaninemia, increased serum pyruvate, ketosis, visual impairment, abnormal skeletal system, abnormal vertebral column, joint hypermobility, scoliosis, abnormal nail, constipation, failure to thrive, vomiting, polyhydramnios. Clinical features manifested at 3.5 years and schizophrenia manifested at 18 years | None | GATA2 c.1017+572C>T p.?, heterozygous, pathogenic | Emberger syndrome; immunodeficiency 21/immunodeficiency | Distinctive | | KDM6B c.1069G>A p.(Gly357Arg), heterozygous, VUS | Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities/developmental delay, ADHD, developmental regression, intellectual disability, hypotonia, joint hypermobility |
| | PKIG00483 | 6-year-old male with intellectual disability, large stem, abnormal legs and hands, speech problem | None | 188.8 kb intragenic del of DYM exons 6-13, heterozygous, pathogenic | Dyggve-Melchior-Clausen disease; Smith-McCort dysplasia/large stem, abnormal legs and hands | Distinctive | | 5.1 kb intragenic del of DYM exon 13, homozygous, pathogenic | | PTCHD1 c.1636C>G p.(Gln546Glu), hemizygous, VUS | Susceptibility to autism 4/intellectual disability, speech problem |
| | PKIG01019 | 1-month-old female with multiple congenital anomalies, pyelectasis, cataract, coloboma, microphthalmia, visual impairment, high arched palate, hyperbilirubinemia, neonatal jaundice, hydronephrosis, abnormal renal morphology, bilateral single transverse palmar creases, respiratory insufficiency, aberrant right coronary artery, suspected Alagille syndrome | None | 11.7 Mb del of 14q31.2q32.12, heterozygous, pathogenic | Bilateral single transverse palmar creases | Distinctive | | RAB23 c.-66+4614dup p.?, heterozygous, VUS | Carpenter syndrome/visual impairment, high arched palate, pyelectasis | | RAB23 c.434T>A p.(Leu145Ter), heterozygous, pathogenic |
| | PKIG01287 [7] | 3-year-old female with ataxia, seizure, encephalopathy, hypertelorism, flat nasal bridge, wide nasal tip; differentials include spinocerebellar ataxia, ataxia telangiectasia, Friedreich ataxia, episodic ataxia, mitochondrial disorders, and inborn errors of metabolism (organic acidemia, urea cycle defect, maple syrup urine disease, CoQ10 deficiency). Clinical features manifested at 35 months | None | 1.5 Mb dup of 16p13.10, likely pathogenic | 16p13.11 microduplication syndrome/seizure | Distinctive | | PC c.2000A>G p.(Lys667Arg), homozygous, VUS | Pyruvate carboxylase deficiency/seizure, encephalopathy |
| | PKIG01703 | 16-month-old female with failure to thrive, hypotonia, global developmental delay, constipation, trigonocephaly, bitemporal narrowing, short nose, anteverted nares, simplified philtrum, low-set ears, joint hypermobility | External CMA, hypotonia panel testing (incl. myotonic dystrophy, SMA, and Prader-Willi syndrome), and fragile X testing: nondiagnostic | PPM1D c.1224dup p.?, heterozygous, likely pathogenic | Jansen de Vries syndrome/failure to thrive, hypotonia, global developmental delay, constipation, anteverted nares, low-set ears | Distinctive | | SCAPER c.1382A>T p.(Asp461Val), heterozygous, VUS | Intellectual developmental disorder and retinitis pigmentosa/global developmental delay | | SCAPER c.1250C>T p.(Ser417Phe), heterozygous, VUS |
| | PKIG01847 | 6-year-old male with Pierre Robin sequence, spasticity, spastic diplegic cerebral palsy, developmental delay, arthrogryposis of lower extremities, redundant nuchal skin, bilateral transverse palmar crease, hair tuft on lower back, tethered spinal cord, focal epilepsy, congenital velopharyngeal insufficiency, toe-walking, myalgias, self-injurious behavior, sleep disturbance, short stature, attention deficit hyperactivity disorder. Clinical features present at birth | External CMA: nondiagnostic
External Stickler syndrome panel testing: COL11A1 VUS reported | WAC c.265_266del p.?, heterozygous, pathogenic | Desanto-Shinawi syndrome/developmental delay, epilepsy, attention deficit hyperactivity disorder, self-injurious behavior | Distinctive | | 11.9 kb intragenic del of PIEZO2 intron 2, heterozygous, VUS | Distal arthrogryposis type 3; distal arthrogryposis type 5; distal arthrogryposis with impaired proprioception and touch/arthrogryposis of lower extremities, Pierre Robin sequence, developmental delay, epilepsy, bilateral transverse palmar crease |
| | PKIG01887 [7] | 3-year-old female with global developmental delay, delayed motor development, delayed language development, developmental regression, intellectual disability, muscular hypotonia, spasticity, epileptic activity, microcephaly, difficulty chewing, difficulty swallowing, poor sucking, severe constipation, gastroesophageal reflux disease, allergies, behavioral issues, grinding, hand biting, repetitive behavior, hyperopia, ankyloglossia. Clinical features manifested at 9 months | External WES: G6PD variant unrelated to phenotype reported | 24.0 kb intragenic del of MECP2 exon 3, heterozygous, pathogenic | Neonatal severe encephalopathy; syndromic intellectual developmental disorder 13; syndromic intellectual developmental disorder, Lubs type; Rett syndrome/global developmental delay, delayed motor development, delayed language development, developmental regression, intellectual disability, muscular hypotonia, spasticity, epileptic activity, microcephaly, difficulty chewing, difficulty swallowing, poor sucking, severe constipation, Gastroesophageal reflux disease, behavioral issues, grinding, hand biting, repetitive behavior | Overlapping features: global developmental delay, delayed motor development, delayed language development, developmental regression, intellectual disability, muscular hypotonia, spasticity, epileptic activity, microcephaly | | DNM1 c.352G>C p.(Val118Leu), heterozygous, VUS | Developmental and epileptic encephalopathy 31A; developmental and epileptic encephalopathy 31B/global developmental delay, delayed motor development, delayed language development, developmental regression, intellectual disability, muscular hypotonia, spasticity, epileptic activity, microcephaly |
| | PKIG02037 | 6-year-old female with focal epilepsy and epileptic syndromes with simple partial seizures, intractable, without status epilepticus, refractory epilepsy, autistic disorder, gray matter and periventricular heterotopia, absent speech, intellectual disability, global developmental delay, optic nerve dysplasia, cortical visual impairment, neurogenic bladder cleft palate, congenital hypotonia, conductive hearing loss, recurrent infections, motor stereotypies, tethered cord syndrome, visual-spatial disorder, toe walking. Clinical features manifested in infancy | External aCGH, Angelman panel test: nondiagnostic
External mtDNA: MT-TL variant reported
External WES: DMXL2 variants and SHANK3 variant reported | MT-TL1 m.3243A>G, heteroplasmic, pathogenic | Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)/epilepsy, hypotonia | Distinctive, overlapping features: epilepsy, hypotonia | | DMXL2 c.7268G>T p.(Arg2423Ile), heterozygous, VUS | Developmental and epileptic encephalopathy 81/epilepsy, absent speech, intellectual disability, global developmental delay, hypotonia | | DMXL2 c.5974G>A p.(Asp1992Asn), heterozygous, VUS |
| | PKIG02059 | 2-year-old male with developmental delay, speech regression, gross motor delay, hypotonia, neutropenia, dysphagia for liquids, supraventricular tachycardia, possible hypothyroidism, progressive sleepiness. Cardiology phenotypes manifested at 1 month | None | COQ8A c.1651G>A p.(Glu551Lys), heterozygous, likely pathogenic | Primary coenzyme Q10 deficiency 4/developmental delay, speech regression, gross motor delay, hypotonia | Overlapping features: developmental delay, speech regression, gross motor delay, hypotonia | | COQ8A c.901C>T p.(Arg301Trp), heterozygous, likely pathogenic | | CIC c.298G>A p.(Ala100Thr), heterozygous, VUS | Intellectual developmental disorder 45/developmental delay, speech regression, gross motor delay, hypotonia |
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