Table 2.
Clinical features of individuals with predicted deleterious variants in PHIP
| Patient no. | 1 | 2 | de Ligt et al. (Trio 5) |
| Current age (yr) | 14 | 8 | UNK |
| Gender | Female | Female | Female |
| Variant | c.50T>C:p.F17S | c.779delT:p.L260Wfs*48 | c.3447T>G:p.Y1149* |
| Prenatal issues | N | N | Meconium stained amniotic fluid |
| Neonatal issues | N | N | Feeding problems |
| Congenital anomalies | Hip dysplasia | Laryngeal cleft | N |
| Dysmorphic features | Fleshy ears, full chin, micrognathia | Fleshy earlobes, small nose, deep-set eyes, up-turned upper lip, short and smooth philtrum, round face | Straight eyebrows, blepharophimosis, mild ptosis, long philtrum, full lips, tapered fingers, clinodactyly of the fifth finger, long toes |
| Birth weight | WT = 3.40 kg (64%) | WT = 3.35 kg (60%) | |
| Current BMI, HT, WT, OFC | At 12 yr 10 mo: BMI = 29.9 kg/m2 (z-score = 2.06) WT = 81.5 kg (99%) HT = 165 cm (89%) OFC = 57 cm (>97%) |
At 8 yr 2 mo: BMI = 23.6 kg/m2 (z-score = 2.08) WT = 39.8 kg (97%) HT = 129.9 cm (59%) OFC = 49.1 cm (4%) |
At UNK age: BMI = 25.4 kg/m2 WT = 56.8 kg (>+2 SD) HT = 149.5 cm (+0.5 SD) OFC = 57.6 cm (>+2.5 SD) |
| Obesity | Y | Y | Y |
| Insulin resistance | Y | N | |
| Developmental delay | Y | Y | Y |
| Age at sitting | 9 mo | 6 mo | 12 mo |
| Age at walking | 18 mo | 14 mo | 24 mo |
| Age at talking | 18 mo | First words at 16 mo, words together by 3 yr, sentences at 4 yr, could not be understood by most people until age 5 | First word at 5 yr |
| Intellectual disabilities | Y | Y | Y |
| Full-scale IQ | 60 | UNK | <50 |
| Current speech abilities | Speaks in full sentences | Nasal speech | |
| ADD | Y | N | |
| Anxiety | Y | Y | |
| Brain MRI/CT results | Unremarkable | Unremarkable | |
| Behavioral issues | N | Y, aggressive toward siblings | |
| Regression | N | N | |
| Hypotonia | Y | Y | |
| Balance/coordination | Poor | Poor | |
| Orthopedic issues | N | N | |
| Gastrointestinal | N | Diarrhea, constipation | |
| Ophthalmologic issues | N | Strabismus | Strabismus |
| Self-care abilities (e.g., dressing, feeding) | Began dressing herself at 9 yr, has trouble with buttons/shoes | Can dress, feed, and help herself but hates utensils, prefers her hands, is sloppy with brushing her hair | |
| Other significant medical problems | Polycystic ovarian disease, menstrual irregularities | Headaches, sleep problems | |
| Additional genetic variants | 5q23.2 duplication, inherited | ||
| Other notes: | Translucent skin on chest/abdomen |
Y, yes; N, no; UNK, unknown; mo, months; yr, years; BMI, body mass index; HT, height; WT, weight; OFC, occipital frontal circumference; %, percentile; ADD, attention-deficit disorder; SD, standard deviations.