Patient data
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | |
|---|---|---|---|---|---|---|
| Sex | M | M | M | F | F | F |
| Parent consanguinity | No | No | No | NA | No | No |
| Family history | Autosomal dominant retinitis pigmentosa (father, paternal aunt, paternal grand- father) | No significant history | NA | NA | No neurologic or developmental disorders, mother with hypothyroidism | No neurologic or developmental disorders, sister with interrupted aortic arch, 2nd cousin with VSD |
| Siblings | Twin brother, normal | Female sibling, normal | NA | NA | NA | None |
| Pregnancy | Twin pregnancy (monozygotic with single placenta) | Singleton pregnancy | NA | NA | Singleton pregnancy | Singleton pregnancy, IUGR |
| Antenatal Imaging | US at 20 w: cerebellar hypoplasia | US at 18 w: cerebellar hypoplasia; at 21w: scoliosis with 2 hemivertebrae | NA | NA | NA | NA |
| Delivery | Elective cesarian birth at 38 w | Elective cesarian birth at 37w | NA | Normal, delayed cry | Cesarean birth for maternal hypertension at 38 w | Cesarean birth for fetal distress at 34 w |
| Birth W/L/HC | 2580 g/47 cm/33 cm | 2450 g/NA/31.8 cm | 2512 g/47.2 cm/31.9 cm | Low weight | 2850 g/NA/32.5 cm | 1493 g/NA/NA |
| Cranial nerve involvement | Bilateral V palsies, bilateral facial weakness (VII), bilateral sensorineural hearing loss (VIII) diagnosed at 18 m | Partial V palsy, possible VI palsy; lower facial weakness, profound high frequency sensorineural hearing loss, VII and VIII palsies | Moderate left hearing loss (VIII) | Bilateral partial V palsies, bilateral VII palsies, bilateral VIII palsies | Bilateral severe sensorineural hearing loss | Bilateral severe sensorineural hearing loss, bilateral absence of the vestibular nerves on MRI, bilateral VII palsy, bilateral V |
| Ocular abnormalities | Oculomotor apraxia, no nystagmus; corneal ulcers | Poor visual fixing, apparent inability to close the eyes, severe corneal drying and right corneal ulcer | Absent corneal sensation bilaterally, vertical nystagmus, abnormal gaze-holding, smooth pursuit, saccades, no vestibular ocular reflexes | Bilateral corneal opacities | Unilateral corneal abrasion leading to corneal opacity, near-absent voluntary eye movements, esotropia requiring bilateral rectus muscle recession | Decreased corneal sensation, impaired smooth pursuit but otherwise normal eye movements |
| Swallowing | Impaired | Impaired | Impaired | Impaired | Impaired | Impaired |
| Feeding | Poor, nasogastric tube followed by gastrostomy at 5 m | Feeding difficulties requiring nasogastric tube | Feeding difficulties | NA | Gastrostomy at 4 m | Feeding difficulties improved with age |
| Cerebellar symptoms | Ataxia | Abnormal movements | Head titubation, uncoordinated movements | Ataxia | Head titubation | Ataxia |
| Pyramidal symptoms | NA | Hypotonia | Mild motor delay | Normal tone and bulk, brisk reflexes | Bilateral ankle clonus | Mildly increased lower extremity tone, brisk reflexes |
| Other neurologic or behavioral findings | None | Mildly dysmorphic features with low set and simple ears, a broad nasal root, a small upturned nose, hypoplastic alar nasae, a long smooth upper lip and mild retrognathia | Bangs forehead on surfaces | NA | None | Unknown |
| Extracranial anomalies | Thoracic scoliosis, numerous hemivertebrae | Vertebral segmentation anomalies on the thoracic and lumbar spine, cocked first toe with a Y-shaped configuration of the second and third toes with minimal syndactyly, horseshoe configuration of the kidneys | None | Erythematous maculopapular skin rash over face, trunk, and limbs | None | Severe narrowing of the auditory canals, membranous VSD, submucous cleft palate, bilateral inguinal hernias, obstructive sleep apnea |
| Global development | Developmental delay noted from early infancy | Failure to thrive | NA | NA | Severe developmental delay | Mild developmental delay: walks with a walker, uses many signs, some ability to read and type |
| EEG | PSG: recurrent central apneas, hypoventilation during REM sleep | Seizures with clonic upper limb movements and facial twitching at 5 w responding to phenobarbital | Excessive multifocal sharp waves, without sustained epileptiform activity | NA | Normal | NA |
| Blood examination | Lysosomal enzymes, very-long-chain fatty acids; serum lactate and pyruvate, Transferrin isoforms and plasma amino acids, normal | Total glycosaminoglycan level slightly elevated | NA | NA | Normal transferrin, deficient glycoprotein testing, mildly elevated CK and liver transaminases | Normal transferrin, deficient glycoprotein testing |
| CSF examination | Lactate and pyruvate slightly elevated | Nonspecific elevation of amino acids | NA | NA | NA | NA |
| Urine examination | NA | Organic and amino acid levels, normal | NA | NA | Urine organic acids, plasma amino acids, normal | Urine metabolic screen normal |
| Karyotype | 46XY | 46XY | NA | NA | 46XX, normal VCFS and subtelomeric FISH testing | 46XX, normal VCFS and subtelomeric FISH testing |
| Latest data | NA | Status epilepticus, hypoglycemia, metabolic acidosis, coagulopathy, and decreased pain response; died at 6 m from parainfluenza pneumonia | 5 months old | 6 months old | Died at 2 years of age from unknown cause | 10 years old |
Note:—NA indicates not available; w, weeks; m, months; W, weight; L, length; HC, head circumference; US, ultrasound; PSG, polysomnography; REM, rapid eye movement; VSD, ventricular septal defect; IUGR, inutero growth retardation; MRI, MR imaging; VCFS, velo-cardio facial syndrome; FISH, fluorescence in-situ hybridization; CK, creatine kinase.