Patient ID | Study site | Age | Sex | Indication for testing | Gene | Variant effect | Disease association (mode of inheritance) | Variant origin | Disease age of onset | Outcome/challenges |
---|---|---|---|---|---|---|---|---|---|---|
1 | SouthSeq | 14 days | M | FTT, renal cyst, developmental hip dysplasia, PFO, retrognathia, possible intracardiac tumors | ABCD1 | p.Arg617Cys | Adrenoleukodystrophy (XLR) | Mat | Childhood to adulthood | Post RoR testing revealed increased VLCFA levels suggestive of adrenoleukodystrophy diagnosis; empowered family and clinicians for additional testing/clinical management |
2 | COAGS | 4 years | M | Dysmorphic features, pseudoform cleft lip, coloboma | ANLN | p.Arg431Cys | Focal segmental glomerulosclerosis (AD) | ND | Childhood to adulthood | Referred to nephrogenetics clinic for further evaluation. Appointment has not yet occurred |
3 | COAGS | 3 years | F | Hydrocephalus, VSD, cleft palate, DD | ATM | p.Val2716Ala | Breast cancer susceptibility (AD); Ataxia-telangiectasia (AR) | ND | Adulthood | Mother requested appointment for cancer genetic counseling and testing, as there is a family history of a maternal grandmother with breast cancer in her 40s. Mother did not keep the appointment and attempt to reschedule were unsuccessful |
4 | COAGS | 8 years | M | Hirschprung disease, ID, obesity | ATM | p.Lys468fs | Breast cancer susceptibility (AD); Ataxia-telangiectasia (AR) | ND | Adulthood | At RoR discussed NCCN guidelines for screening in adulthood. Offered maternal testing for the variant (father not available), but mother declined. There is no family history of cancer in either side of family |
5 | KidsCanSeq | 8 years | M | Medulloblastoma | ATM | p.Asp2959fs | Breast cancer susceptibility (AD); Ataxia-telangiectasia (AR) | Pat | Adulthood | Returned as a primary finding due to nature of study design (see the “Methods” section); Tumor type has no known association with ATM. Given that there was no paternal family history of cancer, no screening was initiated for proband |
6 | SouthSeq | 19 days | M | VACTERL-related features | CACNA1A | p.Arg1545Ter | Episodic ataxia (AD); Epileptic encephalopathy (AD) | Pata | Childhood to adulthood; Birth or early infancy | Post RoR revealed father exhibited symptoms that overlap features reported for CACNA1A- and PMP22-related disorders; Father declined referral to neurology |
6 | SouthSeq | 19 days | M | VACTERL-related features | PMP22, others | 17p12 deletion | Hereditary neuropathy (AD) | Pata | Childhood to adolescence | -- |
7 | COAGS | 5 months | F | Failure to thrive, macroglossia, central and obstructive apnea | CHEK2 | p.Thr367fs | Cancer predisposition (AD) | ND | Adulthood | Mother requested testing for the CHEK2 variant and is negative. Father later reported additional cancer family history that was not initially disclosed at first visit or at initial RoR. He met with genetic counseling, ordered commercial CHEK2 testing, but later canceled the order due to out-of-pocket cost. He was then provided with information about low/no-cost commercial testing, but it is unclear if he completed testing |
8 | P3EGS | Prenatal | F | Fetal heart defect | CHEK2 | p.Arg137Ter | Cancer predisposition (AD) | Mat | Adulthood | Mother referred to genetics; lost to follow up |
9 | COAGS | 4 years | F | DD, esotropia, periventricular heterotopia | SLC3A1 | c.1500+1G>T | Cystinuria (AD, AR) | ND | Childhood to adulthood | Discussed signs and symptoms of the condition at results and will clinically monitor; No family history of symptoms |
10 | P3EGS | 14 months | F | Tracheoesophageal fistula, tethered cord, hypoplastic thumb, microcephaly, small size | COL4A5 | p.Gly1116Val | Alport syndrome (XLD) | Pata | Infancy to adulthood | This variant was not originally formally reported out to the family due to the incidental nature of the finding. However, it was later determined that the father of the proband has a personal history of Alport syndrome and therefore the study requested that the lab look at Alport-associated genes. It was determined that the proband harbored a pathogenic variant in COL4A5 associated with X-linked dominant Alport syndrome. This result was then returned to the family and it was recommended that the proband be followed up with nephrology. |
11 | SouthSeq | 3 days | M | Subcutaneous mass suggestive of lipoma, lymph node or resolving hematoma; maternal family history of having "bumps all over the skin, sometimes painful" | FLCN | 17p11.2 deletion | Birt-Hogg-Dube (BHD) syndrome (AD) | Pat | Adulthood | Originally returned as a primary finding; post RoR, event was clinically validated and determined to be paternally inherited; ultimately classified as an incidental finding. Clinicians are deferring BHD management/surveillance until adulthood |
12 | P3EGS | 17 months | F | Bilateral thumb hypoplasia with family history of Cavanagh syndrome | HFE | p.Cys282Tyr | Hemochromatosis (AR) | Biparental | Adulthood | Parents had difficulty understanding the implications of this unanticipated result and the timing as any effects due to pathogenic variants in HFE are not anticipated until adult life |
12 | P3EGS | 17 months | F | Bilateral thumb hypoplasia with family history of Cavanagh syndrome | HFE | p.His63Asp | Hemochromatosis (AR) | Adulthood | -- | |
13 | COAGS | 5 years | M | DD, epilepsy, autism | HMBS | p.Arg116Trp | Acute Intermittent Porphyria (AD) | Mata | Adolescence to adulthood | Obtained screening urine studies for the patient (pending at specialty lab). Mother requested genetic testing and is positive and referred to GI specialist in porphyria. At RoR discussion, mother endorsed symptoms of porphyria and years of GI scopes/studies which have been non-diagnostic |
14 | COAGS | 15 years | M | Tremor, autism, hypernasal speech, congenital heart defect | HOXB13 | p.Gly84Glu | Hereditary prostate cancer (AD) | ND | Adulthood | Mother reported that she shared copies of the child's report with both maternal and paternal relatives as it is unknown if/from whom the variant was inherited |
15 | P3EGS | 3 years | F | ID/NDD | MC4R | p.Ile269Asn | Obesity (AD) | Pata | Infancy | Paternal family members exhibit obesity |
16 | COAGS | 6 years | M | DD, failure to thrive, dysmorphic features | MFN2 | p.Arg707Trp | Charcot-Marie-Tooth disease (AD, AR) | ND | Childhood to adulthood; Infancy/early childhood | Discussed signs and symptoms of the condition at RoR and will clinically monitor. No family history of symptoms |
17 | COAGS | 18 years | F | DD/NDD, short stature, hirsutism, dsymorphic features | MITF | p.Glu425Lys | Susceptibility to cutaneous malignant melanoma (AD) | ND | Adulthood | Discussed surveillance and skin protection at RoR. No family history of melanoma |
18 | SouthSeq | 25 days | F | IUGR, congenital microcephaly, congenital hearing loss, cardiomyopathy, thrombocytopenia, intraabdominal abcess, mid jejunal necrosis/perforation | PRRT2 | p.Arg217Pfs | Episodic kinesigenic dyskinesia (AD); Benign familial infantile seizures (AD) | ND | Childhood to adolescence | Donor egg; parents did not want findings placed in the EHR but encouraged to share with infant's health care providers; Patient is followed in Neurodevelopmental Clinic and Early Steps |
19 | SouthSeq | 24 days | M | Cardiac and urogenital anomalies | SCN4A | p.Ile1455Thr | Paramyotonia congenita (AD) | Pata | Infancy to early childhood | Post RoR, revealed father exhibited symptoms that overlap features reported for SCN4A-related condition and was excited to learn of why he has stiffness regularly |
20 | COAGS | 9 months | M | Dysmorphic features, dysphagia, hip dysplasia | SLC6A5 | p.Cys3Ter | Hyperekplexia (AD, AR) | ND | Newborn to infancy | Family reported no history of symptoms of the condition |
21 | COAGS | 5 years | M | Cutis verticis gyrata, bifid uvula, autism-like behaviors | SLC7A9 | p.Gly105Arg | Cystinuria (AD, AR) | ND | Childhood to adulthood | Post RoR, reported family history of multiple people with kidney stones. Alerted pediatrician to monitor if symptoms arise |