Table 1:
Clinical and Molecular Findings in Individuals Carrying SPEG Mutations
| Patient/Sex | P1/M (this study) | P2/F (this study) | P3/F9 | P4/F9 | P5/M9 | P6/M10 | P7/M10 | P8/M12 | P9/M11 |
|---|---|---|---|---|---|---|---|---|---|
| Age (when reported) | Died at 17 years | 6.5 years | Died at 3 weeks | 6 years | 1.5 years | 3 years | 7 years | 10 years | Died at 19 weeks |
| SPEG exons | Exon 38 | Exon 10 and 38 | Exon 30 | Exons 18 and 13 | Exons 10 and 35 | Exon 4 | Exon 40 | Exon 4 and 20 | Exon 30 |
| Allele 1 (maternal) | c.9185_9187delTGG; p.Val3062del | c.2183delT; p.Leu728fs | c.6697C>T; p.Gln2233* | c.4276C>T; p.Arg1426* | c.2915_2916delCCinsA; p.Ala972fs | c.1627–1628insA; p.Thr544fs | c.9586C>T; p.Arg3196* | c.1071_1074dup; p.Lys359fs | c.7119C>A p.Tyr2373* |
| Allele 2 (Paternal) | same as above | c.8962_8963ins25; p.Val2997fs | same as above | c.3709_3715+29del36; p.Thr1237fs | c.8270G>T; p.Gly2757Val | same as above | same as above | c.4399C>T; p.Arg1467* | same as above |
| Family History | Consanguineous parents, one healthy sister | No known consanguinity | Consanguineous parents, two sisters died early | No known consanguinity | No known consanguinity, sibling died early | parents from village in Turkey | Likely consanguineous | Non-consanguineous | Consanguineous parents |
| Birth History | Full term, severely hypotonic | Full-term, hypotonic | Full-term, breech delivery, severely hypotonic | Severely hypotonic | Born at 36 weeks of gestation, severely hypotonic | Full-term, hypotonic | Full-term, poor fetal movements | Uneventful pregnancy, hypotonic | Uneventful pregnancy, severely hypotonic |
| Neurological Findings | symmetric atrophy of lower extremities, wheel chair bound at 17 years | normal early motor milestones, walked at 2 years, unable to run or jump | Died of severe muscle weakness | Sit unsupported at 2.5 years, unable to walk unsupported | Head control at 16 months, sit unsupported at 18 months | Head control - 6 months, sit unsupported - 12 months, unable to walk | Head control at 18 months, sitting at 30 months, walking- 4 years | sit −11 months, walk - 30 months, short distances | Contracture of right ankle and lacked deep tendon reflex, antigravity movement at 1 week |
| Eye Findings | Ophthalmoplegia | Ophthalmoplegia, bilateral ptosis | No known evaluation | Ophthalmoplegia | None | ophthalmoplegia, mild ptosis | None | None | None |
| Respiratory Issues | non-invasive ventilation during night, recurrent pneumonia | Weak cough | Insufficient respiratory efforts | Tracheostomy, mechanical ventilation dependent | brief NICU stay for respiratory issues, no assisted ventilation | NICU for apnea, no intubations, recurrent lung infections | non-invasive ventilation during first 48 hours of life | None | Intubation required immediately after birth, weaned at 10 weeks for palliative care |
| Feeding Issues | Gastrostomy tube from age 6 | gastrostomy tube | Gastrostomy tube early in life | Gastrostomy tube early in life | NG feeding | None | NG feeding until day 13 | Gastrostomy tube from age 9 | Gastrostomy tube |
| Cardiac Issues | Dilated cardiomyopathy at age 7, severe mitral valve insufficiency | No cardiomyopathy at 3 years 10 months, sinus tachycardia | No cardiac evaluation | Dilated cardiomyopathy | Dilated cardiomyopathy, mitral valve insufficiency | None | Dilated cardiomyopathy mild mitral insufficiency | Reduced myocardial contraction, no ventricular dilation at 5 year | Enlarged atria, abnormal trabeculation of left ventricle |
| Skeletal Issues | Torsion scoliosis | Ulnar fracture at age 4, condyle fracture at age 5, tibia fracture at age 11 (all after trauma) | Not applicable | None | None | Pectus excavatum and mild scoliosis | None | Scoliosis developed at age 4 | Not applicable |