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Table 1 Parental age at conception and gestation, and phenotypes of affected subjects and of typical BOS.

From: De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome


Subject 1

Subject 2

Subject 3

Subject 4


Parental age, years







38 2/7 weeks; poor fetal growth; polyhydramnios

39 weeks, breech birth

38 weeks, C-section

40 weeks, spontaneous vaginal delivery


Size at birth




Weight 50%; length 25 to 50%

Approximately 1%


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

  1. aCGH, array-comparative genomic hybridizationl BOS, Boehring-Opitz; CPK, creatine phosphokinase; G-tube; gastric tube; MCP, metacarpophalangeal; MECP, methyl CpG binding protein; MR, magnetic resonance; OFC, occipitofrontal circumference; SD, standard deviation; SNP, single-nucleotide polymorphism.
  2. Features shared by at least two subjects and BOS are in italics.