Table 1.
Clinical Features of Individuals Carrying HNRNPR Variants
| This Study | Previously Published Case23 | ||||
|---|---|---|---|---|---|
| Individual 1 (P1) | Individual 2 (P2) | Individual 3 (P3) | Individual 4 (P4) | Individual 5 (P5) | |
| hnRNPR variant | c.1609dupG (p.Ala537Glyfs∗10) | c.1652dupG (p.Pro552Serfs∗34) | c.1652dupG (p.Pro552Serfs∗34) | c. 1763G>A (p.Arg588His) | c.1663C>T, (p.Gln555Ter) |
| Sex | f | m | f | m | NA |
| Age at last follow-up | 12 years | 3 years | 10 years | 8 years | infant |
| Height (percentile) | 140 cm (90th) | 83 cm (<1st) | 112.4 cm (3rd) | 101 cm (<1st) | NA |
| Weight (weight per height percentile) | 43 kg (95th) | 10.6 kg (10th) | 23.8 kg (95th) | 13.4 kg (<1st) | NA |
| Head circumference (percentile) | 49 cm (<1st; 50th at birth) | 44 cm (<1st; 30th at birth) | 44,5 cm (3rd; unknown at birth) | 48 cm (<1st; 50th at birth) | NA |
| Neurological Features | |||||
| Developmental delay | severe | moderate to severe | moderate (IQ 52) | severe | + |
| Seizures | + (febrile) | + | + | − | + (epileptic encephalopathy) |
| Generalized hypotonia | + | − | + | + | NA |
| Brain abnormalities; magnetic resonance imaging | short corpus callosum (conserved proportions with microcephaly) | hypoplastic corpus callosum, frontal atrophy, cerebellar vermis hypoplasia | microcephaly | short corpus callosum, cerebellar vermis hypoplasia, microcephaly | corpus callosum agenesis, cerebellar vermis hypoplasia |
| Behavior | Stereotypic movements, attention deficit disorder | Stereotypic movements, attention deficit disorder | Stereotypic movements, pervasive developmental disorder | − | NA |
| Cardiac defects | − | VSD | − | − | NA |
| Urogenital defects | − | cryptorchidism, micropenis | hypoplastic labia | − | NA |
| Facial dysmorphism | + | + | + | + | mild |
| Unusual head hair 1st year of life | + | + | + | NA | NA |
| Brachycephaly | − | + | + | + | NA |
| Face shape | bitemporal narrowing | round, bitemporal narrowing | angular lower facies, round face | round face | NA |
| Ear abnormalities | + | + | + | + | NA |
| Upslanted palpebral fissures | + | + | + | − | NA |
| Telecanthus | − | + | − | − | NA |
| Short palpebral fissures | + | + | − | − | NA |
| Abnormal nasal bridge | wide | depressed | narrow | − | NA |
| Low columella | − | − | + | + | NA |
| Tooth abnormalities | + | + | + | − | NA |
| Micrognathia and/or retrognathia | − | + | + | + | NA |
| Short and/or broad neck | − | + | + | − | NA |
| Thorax and/or Spine | |||||
| Rib abnormalities | − | 11 rib pairs | Hypoplastic 12th rib pair; abnormal articulation of the costovertebral junction and ribs | − | NA |
| Abnormalities in vertebra and/or pelvis | coxa valga | hip dysplasia | Subtle narrowing interpediculate distance lumbosacrally, increased cartilage pelvis, widening symphysis pubis, scoliosis | − | NA |
| Extremities | |||||
| Short hands | − | + | + | + | NA |
| Short feet | + | + | + | − | NA |
| Pes valgus | + | − | − | + | NA |
| Brachydactyly | + | + | + | + | NA |
| Broad thumb and/or big toe | + | ± | ± | − | NA |
| Clinodactyly in digit 2 of the hands and feet | + | + | − | − | NA |
| Hypoplastic end phalanges of the fifth digit and/or toe and clinodactyly | + | + | + | + | NA |
| Eye Abnormalities | |||||
| Abnormal retina | − | Pale retina, pale papillae | − | Pale retina | NA |
| Oculomotor defects | − | − | + | − | NA |
| Nystagmus | − | + | − | − | NA |
| Hypermetropia | + | − | + | − | NA |
| Strabismus | + | + | + | − | NA |
| Others | |||||
| Hearing loss | − | − | − | − | NA |
| Laryngomalacia | − | + | ± | − | NA |
| Feeding difficulty | + | ++ | ++ | + | NA |
| Precocious puberty | + | suspected | − | − | NA |
| Hirsutism | + | + | + | − | NA |
A list of the molecular variants in HNRNPR and the clinical features described in four unrelated individuals (P1–P4) in this study, plus one previously reported individual (P5).23 NA = not available and VSD = ventricular septal defect.