Table 1.
Clinical description and comparison of affected individuals carrying a homozygous mutation in ICK
| Clinical features | Present fetus | Affected individuals combined/updated from Lahiry et al. [1] |
|---|---|---|
| Pt I | IV-1, 2, 3, 4, 7, 8, new | |
| Age at delivery (weeks) | 33 | Range 24–34 |
| Karyotype | 46, XY | 46 (6/6), XY (4/6), XX (2/6) |
| Height (centile) | 41 cm (10–25th) | 3rd–10th (3/5), 90th–97th (2/5) |
| Weight (centile) | 2450 g (90–97th) | 90th–98th (5/7), 10th–25th (2/7) |
| Head circumference (centile) | 34 cm (>97th) | 90–>98th 4/6), 3rd–20th (2/6) |
| Autopsy | − | + (3/6) |
| Oral | ||
| Cleft palate | Cleft soft palate | Midline (5/6), notch in alveolar (1/6) |
| Cleft lip | Midline notching | Midline (5/7), bilateral (2/7) |
| Presence of premaxilla | + | + (2/6) |
| Prominent upper lip region | − | + (2/6) |
| Hypoplastic/absent epiglottis | Unknown | + (2/3) |
| Hypoplastic/absent larynx | Unknown | + (2/3) |
| Craniofacial | ||
| Dolichocephaly | − | + (3/6) |
| Midface hypoplasia | + | + (6/6) |
| Microphthalmia | + | + (4/6), cystic (2/6) |
| Retinal dysplasia | Unknown | + (1/3) |
| Deep set eyes | + | + (5/5) |
| Fused eyelids | − | + (1/6) |
| Hypotelorism | − | + (1/1) |
| Flat and wide nasal bridge | + | + (6/6) |
| Dysplastic and low-set ears | + | + (5/5) |
| Micrognathia | + | + (6/6) |
| Excess skin below chin | − | + (4/6) |
| Single nostril | − | + (1/1) |
| Natal teeth | + | + (1/6) |
| Limbs-thorax | ||
| Micromelia | +, severe | + (7/7) |
| Polydactyly (postaxial) | Upper limbs, heptadactyly | + (6/6) |
| Polydactyly (preaxial) | Lower limbs, heptadactyly | − |
| Brachydactyly | +, Severe | + (6/6) |
| Syndactyly | 4 limbs, total syndactyly | + (7/7) |
| Hitch-hikers’ thumbs | − | + (1/6) |
| Palmar creases abnormalities | Irregular, vertical creases | + (3/3) |
| Ulnar deviation of hands | − | + (6/6) |
| Bowing of forearms | + | + (6/6) |
| Bowing of lower legs | − | + (2/6) |
| Abducted hips | + | + (6/6) |
| Sandal gap | − | + (6/6) |
| Talipes equinovarus | + | – |
| Chest width | Narrow | Broad (1/6), narrow (1/6) |
| Prominent xyphoid | − | + (1/6) |
| Radiography | ||
| Abnormal long bones (radius, ulna, tibia, fibula) | Very short with bowed radii and more severe involvement of the lower limb | Short diaphysis (1/1) |
| Short and incurved ulnae | + | + (1/1) |
| Short and ovoid tibiae | Very short, with very short fibula | + (1/1) |
| Abnormal humerus | Very short | Short diaphysis (1/1) |
| Abnormal femur | Very short, torpedo-like | Short and ovoid (1/1) |
| Spondylar involvement | +, Mildly defective ossification | Unknown |
| Premature epiphyseal ossification | +, Knees | Unknown |
| Abnormal ilium | Small ilia with normal contour | + (1/1) |
| Abnormal/hypoplastic acetabular roof | − | + (1/1) |
| Central nervous system | ||
| Evidence of holoprosencephaly | − | + (4/4) |
| Corpus callosum | + | + (3/3) |
| Absence of septum pellucidum | + | + (2/2) |
| Hydrocephalus (ventriculomegaly) | + | + (2/2) |
| Dysmorphic cerebral aqueduct | Unknown | + (2/2) |
| Olfactory bulbs | Unknown | + (2/2) |
| Cerebral cortex malformation | Unknown | + (3/3) |
| Brainstem malformation | Unknown | + (3/3) |
| Cerebellar abnormalities | − | + (2/2) |
| Hippocampus agenesis | Unknown | + (2/2) |
| Leptomeningeal glioneuronal heterotopia | Unknown | + (1/1) |
| Spinal cord malformation | Unknown | + (1/2) |
| Endocrine system | ||
| Pituitary gland | Unknown | + Absent (2/2) |
| Adrenal glands | Unknown | + Absent (1/3), hypoplastic (2/3) |
| Other | ||
| Polyhydramnios | − | + (1/6) |
| Fetal hydrops | + | − |
| Pulmonary hypoplasia | Unknown | + (1/1) |
| Congenital heart defect | +, VSD | − |
| Gastrointestinal anomalies | Unknown | + (2/3) |
| External genitalia abnormalities | Sex reversal with hypoplastic labial folds | + (4/7) |
| Cryptorchidism | n/a | + (1/6)c |
| (Hyper)echogenic kidneys | + | + (3/6) |
| Large kidneys | + | + (1/6)d |
| Squamous metaplasia of bladder | Unknown | + (1/3) |
Blank cells indicate that information was unavailable
a Information gathered from attending-physician reports
b Report from International Skeletal Dysplasia Registry (Cedars-Sinai Medical Center) for patient 1
c Feature is reported as patient had ambiguous external genitalia
d Large kidneys displayed cystic tubules