Table 2.
Characteristics and results for newborns referred to molecular testing organized by resolution.
| Case * | Diagnosis | Sex | Screen Result CK-MM (ng/mL) | Molecular Result | Case Summary |
|---|---|---|---|---|---|
| R-5 | DMD | M | 7809 | DMD dup ex18 (LP) | Molecular diagnosis of Duchenne/Becker muscular dystrophy. Followed in MDA clinic. Last visit at 17 months: out-toes but no toe walking. With support can raise self-off floor. Cannot assess if Gower sign is present. Appears to have trouble raising body with use of one leg. Physical therapy 2x per week and development therapy 1x per week. No medications. |
| R-6 | BMD | M | 6384 | DMD del ex48-49 (LP) | Followed in MDA clinic. No cognitive or motor delays identified at 7 months. Sequencing result is consistent with a deletion of this region of the gene and predicted to result in in-frame deletion in the DMD mRNA. This is consistent with a diagnosis of DMD/BMD. The subject’s maternal grandfather was diagnosed with molecularly confirmed BMD. His symptoms started in mid-life. |
| R-15 | DMD | M | 18,574 | DMD del ex3-43 (LP) | Not screened as a newborn. Referred to genetics and enrolled in study because of family history of DMD, markedly elevated CK, and troponin T suggestive of congenital myopathy and hydronephrosis. DMD and gene panel ordered concurrently. |
| R-8 | Alagille Syndrome | F | 4370 | JAG1 (P) | CK normalized at 4 months. Baby had a congenital heart defect and very high liver enzyme. Clinical genetics evaluation revealed JAG1 pathogenic variant consistent with Alagille syndrome. |
| R-12 | None | F | 4150 | SGCA, (P), het; TTN (VUS), het | Normalized CK and no evidence of muscle weakness at 1 month. Family received genetic counseling regarding AR inheritance of limb girdle muscular dystrophy and was offered parental testing. |
| R-9 | None | F | 6007 | GNE c.218G>A, (P), het; POMT1 (VUS), het; TTN (VUS) x 3, het | CK not repeated. Clinical evaluation showed no evidence of sialuria. |
| R-3 | None | F | 4895 | DMD 17 kb del intron 55 (VUS), het; RYR1 (VUS), het | Normalized CK and no evidence of weakness at 9 months. |
| R-10 | None | F | 5365 | LAMA2, (VUS), het | CK not repeated. Declined further follow-up care. |
| R-11 | None | M | 4154 | TTN, (VUS), het | Normalized CK and no evidence of weakness at 1 month. |
| R-13 | None | M | 5128 | SIL1, (VUS), het | CK not repeated. Declined further follow-up care. |
| R-14 | None | F | 12,002 | AMPD1, (VUS), het | CK was not repeated. Family moved out of state. |
| R-16 | None | F | 4507 | RYR2, (VUS), het; TTN, (VUS), het | CK normalized at 9 days. Declined further follow-up care. |
| R-4 | None | M | 4850 | DYSP, (VUS), het PLEC, (VUS), het RYR2, (VUS), het | Normalized CK at 10 days. At birth there was a concern for inborn error of metabolism because of the standard newborn screening panel. Complete metabolic workup and exome sequencing with mitochondrial genome seq/del were negative. |
| R-7 | None | F | 5054 | Declined testing | Parents report normal development at 7 months. Declined molecular testing. |
| R-1 | LTFU | M | 4593 | NA | Unknown. |
| R-2 | LTFU | F | 8399 | NA | Unknown. |
* Case numbers derived from the referral to molecular testing order e.g., the first case referred for molecular testing is R-1. F = female; M = M=male; LP = likely pathogenic; VUS = variant of unknown significance; P = pathogenic; NA = not applicable; CK = creatine kinase; DMD = dystrophin; JAG1 = jagged canonical notch ligand 1; SGCA = sarcoglycan alpha; TTN = titin; GNE = glucosamine (UDP-N-acetyl)-1-epimerase/N-acetylmannosamine kinase; RYR1 = ryanodine receptor 1; LAMA2 = laminin subunit alpha 2; SIL1 = SIL1 nucleotide exchange factor; AMPD1 = adenosine monophosphate deaminase 1; RTR2 = putative protein serine/threonine phosphatase; LTFU = lost to follow-up.