Table 2

Characteristics of the probands with breakpoints in genes with known impact on phenotype

Proband 6Proband 7Proband 8Proband 9
Current age8 years5 years10 months34 years
Karyotype46, XY,t(10;22)(q26.1;q12.3)46,XX,t(1;16)(p13.2;q13)46,XY,t(5;8)(p13;q21.2)46,XY,t(2;8)(q31;q24.1)
Implicated gene(s) EBF3, LARGE ZNF423 NIPBL TRPS1
MIM number* 607407 (EBF3), 603590 (LARGE)604557608667604386
WESNoNoNoNo
Physical parametersLow birth weight, currently normalNormal at birth, FTT, currently low weight and short for agePrenatal growth retardation, low birth weight (1840 g). Recently failure to thrive, low weight, low-pitched, growling cry in infancy, sensorineural hearing loss.Normal
ID/DDModerateModerateModerateNot observed
Other neurological featuresNeonatal hypotonia and later hypertonicity, speech delay, ADHD, fits of anger, abnormal EEGHypotonia, sound hypersensitivity, hyperactivity, speech delay, autistic featuresHypertonia in neonatal period, psychomotor developmental delayNone
Congenital anomaliesTotal anomalous pulmonary venous return (TAPVR)Hypoplastic thumbs, unilateral thumb symphalangism, strabismus and hyperopia, brain MRI (at 5 years): slightly dilated frontal horns and bodies of the lateral ventricles, small anterior pituitary lobeFour hypoplastic fingers and a single transverse palmar crease on the left hand; bilateral cryptorchidism; atrial septal heart defect (ASD), gastro-oesophageal reflux, hirsutismNone
DysmorphismTall forehead, straight eyebrows, narrow palpebral fissures, unilateral epicanthic fold.
Anteverted short nostrils, thin lips with downturned corners of the mouth, short and broad chin, short hands, pes planovalgus, square toes with sandal gap.
Short palpebral fissures, telecanthus, flat and wide nose, hypoplastic nasal alae, low-set ears, micrognathia, high palate, hypertelorism.Typical CdLS phenotype: microcephaly, synophrys, deep-set eyes, long eyelashes, long and prominent philtrum, microretrognathiaTypical frontal bulbous pear-shaped nose, broad philtrum, thin upper lip, large ears, hand and foot brachydactyly, broad thumbs and big toes, funnel chest
Diagnosis EBF3 delayed development syndrome (MIM: 617330)Atypical disease from the ZNF423 spectrum (MIM: 614844)?Cornelia de Lange syndrome (MIM: 122470)Trichorhinophalangeal syndrome (MIM: 190350)
OtherUrinary bladder malfunction, coprophiliaNoneNoneNone
  • *Online Mendelian Inheritance in Man (OMIM, https://www.omim.org/).

  • ADHD, attention-deficit/hyperactivity disorder; DD, developmental delay; EEG, electroencephalography; FTT, failure to thrive; ID, intellectual delay; WES, whole-exome sequencing.