Table I.
Patient Characteristics
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | NS-LAH [summarized Table I in Gripp et al., 2013] |
|
|---|---|---|---|---|---|
| PPP1CB mutation | De novo p.Pro49Arg |
De novo p.Ala56Pro |
De novo p.Pro49Arg | De novo p.Pro49Arg |
N/A |
| Sex | Male | Male | Female | Female | N/A |
| Age at last evaluation or contact |
5 3/12 years | 9 years | 4 7/12 years | 21 years | N/A |
| Polyhydramnios | - | - | - | - | 4/7 |
| Increased birth weight |
- | - | - | - | 3/7 |
| Short stature | + | + | + | - | 28/31 |
| Macrocephaly | Relative | Relative | Relative | + | 29/32 |
| Feeding difficulties | + | Neonatal | Neonatal | - | N/A |
| Feeding tube use | + | Neonatal | Neonatal | - | 3/5 |
| Delayed development |
+ | + | + | + | 5/5 |
| Hypotonia | - | Mild | + | - | 4/5 |
| ADHD/cognition and behavior |
Anxious | Slow processing | - | Very active, impulsive, anxious |
ADHD 14/22 |
| Down-slanted palpebral fissures |
+ | Mild | - | - | N/A |
| Hypertelorism | + | - | + | + | N/A |
| Epicanthus | - | - | + | - | N/A |
| Low-set, posteriorly angulated ears |
+ | + | + | + | N/A |
| Pulmonic valve stenosis |
- | - | + | N/A | 11/29 |
| Mitral/tricuspid valve anomaly |
Mitral valve thickening |
- | - | N/A | 9/28 |
| ASD/VSD | - | - | - | N/A | 10/25 ASD |
| Hypertrophic cardiomyopathy |
- | - | - | N/A | 6/29 |
| Pigmentation | Freckling | Café-au-lait lesions |
Irregular hypopigmentation on back |
- | 23/31 |
| Slow growing hair | + | - | + | + | 19/19 for any manifestation of LAH |
| Curly hair | + | - | - | - | |
| Unruly hair texture | + | + | - | + | |
| Hemangioma | - | - | Large, on chin | - | 2/5 |
| Eye anomalies | Proptosis, tear duct stenosis |
Strabismus repair |
- | Optic nerve hypoplasia, nystagmus, impaired vision |
N/A |
| Hearing loss | - | Possible | Mild | - | N/A |
| Webbed/short neck |
- | Short | - | - | N/A |
| Pectus anomaly | - | + | - | - | N/A |
| GU anomaly | cryptorchidism | - | N/A | N/A | N/A |
| Malignancy | - | - | - | - | Myelofibrosis in 1 |
| Other | Redundant arytenoid tissue; right bundle branch block |
N/A | prenatal edema of face and neck; hirsutism on back; coxa valga bilaterally |
Dandy-Walker malformation; preauricular pits (familial) |
N/A |
| Genetic testing with normal results |
46, XY Array CGH |
Array CGH Mitochondrial DNA |
SNP array, TSH and CK, urine oligosaccharide and free glycan, lysosomal enzymes |
N/A | N/A |
| Normal sequence results |
BRAF, HRAS KRAS, MEK1 MEK2, SHOC2 NRAS,PTPN11 SOS1, RAF1 CBL, RIT1 |
BRAF, HRAS KRAS, MEK1 MEK2, SHOC2 NRAS,PTPN11 SOS1, RAF1, CBL RIT1 |
BRAF, HRAS, KRAS MEK1, MEK2, SHOC2 NRAS, PTPN11, SOS1 RAF1, CBL (maternally inherited VUS in BRAF) NM_004333:c.967T>C(p. Ser323Pro) |
N/A | N/A |
ASD: Atrio-septal defect. N/A: Not available or not assessed. NS-LAH: Noonan syndrome with loose anagen hair. LAH: Loose anagen hair.VSD: Ventriculo-septal defect.