Subject 1 | Subject 2 | Subject 3 | Subject 4 | BOS | |
---|---|---|---|---|---|
Parental age, years | 45/44 | 30/29 | 24/29 | 26/26 | |
Gestation | 38 2/7 weeks; poor fetal growth; polyhydramnios | 39 weeks, breech birth | 38 weeks, C-section | 40 weeks, spontaneous vaginal delivery | |
Size at birth | ~1% | ~1% | 40% | Weight 50%; length 25 to 50% | Approximately 1% |
Gastrointestinal | Gastric tube feeds for 8 months, gastro-esophageal reflux | Gastric tube feeds first month | No obvious difficulties | Difficulty latching on from birth; poor oral feeding resulted in admission at age 8 weeks for failure to thrive; gastro-esophageal reflux; Nissen fundoplication and G-tube placed | Feeding difficulties |
Craniofacial features | Arched, thin eyebrows; high, narrow palate; low, posteriorly rotated ears; microcephaly; anteverted nares, large fontanels; retroganthia; long eyelashes | Arched eyebrows; high, narrow palate; low, posteriorly rotated ears; microcephaly; anteverted nares; hypertelorism; short nose; gingival hyperplasia; sparse hair; scaly scalp; hyperopia | Prominent forehead/frontal bossing; short nose with anteverted nares | Prominent forehead; arched eyebrows; hypoplastic alae nasi; low-set ears; high and narrow palate | High, narrow palate; low-set, posteriorly rotated ears; microcephaly; trignocephaly; anteverted nares; prominent eyes; upslanting palpebral fissures; depressed nasal bridge |
Somatic features | Ulnar deviation of hands at rest; deep palmar and plantar creases; hypertonia; bladder dysfunction; testes normally descended | Ulnar deviation of hands; deep palmar creases; hypotonia; clenched hands; undescended testes | Mild global hypotonia | Exotropia; hirsutism; supranumerary nipple; low truncal tone with abnormally fluctuating tone in limbs; no clonus; mild ulnar deviation of the hands; deep palmar creases and clenching of hands, less prominent over time | High myopia; hirsutism; 'BOS' posture: exorotation and/or adduction of the shoulders; flexion at the elbows; flexion at the wrists; and ulnar deviation of the hands and/or fingers at the MCP joints |
Post-natal growth & development | Weight, length & OFC all -4.5 to -5.0 SD; psychomotor delay. Died aged 9 months. | Size < 1%; a severe psychomotor delay | Normal growth; global developmental delay with intellectual disability | Age 41.5 months: OFC < 2nd%; 50th % for age 1 year; Length, weight 10 to 25 th percentile; unable to sit independently; non-verbal; no sign language; mostly G-tube fed | Growth retardationa; psychomotor delay; high rate of infant mortality |
Brain imaging results | Global mild white-matter volume loss with normal myelination; secondary brainstem hypoplasia; hypoplasia/dysplasia of bilateral cerebellar tonsils; mild inferior vermian hypoplasia; normal MR spectroscopy | Enlarged ventricles, agenesis of corpus callosum, Dandy-Walker malformation, delayed myelination and cortical atrophy | |||
Laboratory testing with non-diagnostic results | NIPBL sequencing (Cornelia de Lange) | aCGH; urine oligosaccharide; sequencing panel for Noonan, Prader-Willi, cardiofaciocutaneous, and Costello syndromes; thin-layer chromatography for fucosidosis, mannosidosis, aspartylglucosaminuria, GM1- and GM2-gangliosidosis, galactosialidosis, Schindler and Pompe disease; [AU What does 'M' stand for here? Are these Schindler disease and Pompe disease? Ms have been removed ] electrophoresis for congenital disorders of glycosylation | SNP aCGH; methylation for Angelman; plasma and urine creatine and guanidinoacetate; urine purine and polyol panels; plasma homocysteine | 46, XX; SNP aCGH; Sequencing panel for congenital disorders of glycosylation; N-glycans; methylation for Angelman syndrome; MECP2 sequencing; muscle biopsy gave normal electron and light microscopy results; urinary organic acids; plasma amino acids; CPK |