Table 1. Clinical features of patients.
ASD, atrial septal defect; IUGR, intrauterine growth retardation; SGA, small for gestational age; OFC, occipito-frontal circumference; PCC, premature chromosome condensation; cMRI, cranial magnetic resonance imaging, ID, intellectual disability; IQ, intelligence quotient; SNP, single-nucleotide polymorphism; CGH, comparative genomic hybridization; MLPA, multiplex ligation-dependent probe amplification.
| P1 | P2 | |
| BUB1 variants: NM_004336.4 | c.[2T>G];[2T>G] | c.[2625+1G>A] mat;[c.2197dupG] pat |
| Protein | p.[?];[?] | p.[V822_L875del];[D732fs*11] |
| Zygosity | Homozygous | Compound heterozygous |
| Mutation detected by | Exome | Exome |
| Gender | Male | Female |
| Age at last assessment | 3 years 10 months | 16 years 10 months |
| Prenatal | Enlarged nuchal translucency, IUGR, Pierre-Robin sequence |
No complications |
| Birth | ||
| Delivery | Normal | Sec. caesarean section due to fetal distress |
| Gestational week | 39 + 4 | 38 + 5 |
| Length in cm (SD*) | 45 (−3) | 46 (−2,8) |
| Weight in g (centiles†) | 2400 (0.4th–2nd) | 2825 (9th–25th) |
| OFC in cm (SD*) | 32 (−2,8) | 31 (−2,9) |
| Growth | ||
| Stature | SGA, short stature | Slight growth retardation |
| Length in cm (SD*) | 89 (−3) under growth hormone substitution since age 3 years 4 months |
152,8 (−2) |
| Weight in kg (centiles) | 11 (<0.4th) | 74.5 (91st–99th) |
| OFC in cm (SD*) | 41.5 (−7 SD) | 49.5 (−4,9) |
| Head and neck | ||
| OFC | Microcephaly | Microcephaly |
| Ear | Asymmetric ears, uplifted earlobes | No abnormality |
| Eye | Epicanthic folds, long palpebral fissure | Axenfeld Rieger anomaly both eyes, also present in father (posterior embryotoxon–anterior synechiae) |
| Face | Pierre-Robin sequence | No abnormality |
| Mouth | Clefting of soft palate, thin upper lip, small mouth, difficulties with chewing |
No abnormality |
| Cardiovascular | Small ASDII | Small ASDII |
| Respiratory | Long tracheal stenosis, tracheostoma | Bronchial obstruction after viral infection |
| Genitourinary | Hypospadia | No abnormality |
| Skeletal | ||
| Scull | Choanalstenosis | No abnormality |
| Hands | Clinodactyly fifth finger | No abnormality |
| Feet | Sickle feet as baby, sandal gaps | Broad feet, sandal gaps |
| Skin, nails, and hair | ||
| Skin | No abnormality | Acanthosis nigricans neck, two cafe au lait spots |
| Hair/teeth | No abnormality | Small teeth, remarkably light hair color compared to parents |
| Neurologic | ||
| Brain imaging | cMRI at age 1 year: symmetrical supratentorial cortical atrophy, enlarged ventricles |
Not available |
| Developmental delay/ID | Yes | IQ 68, mild intellectual disability |
| Age of walking | 1 year 10 months | 18 months |
| First words/current speech | 3 active words at the age of 4 years, communication with gestures |
Started talking “late,” had speech therapy. With help, she is able to write a few simple words, but reading is difficult (she does not understand what she reads). |
| Behavior | Happy and friendly | Normal, quiet mental state |
| Endocrine feature | Growth hormone deficiency, supplemented since age 3 years and 4 months |
Obesity |
| Other | Hernia inguinalis | |
| Normal laboratory findings | Normal results for: invasive prenatal diagnostics (SNP array) and postnatal array CGH from blood |
Normal results for: MLPA telomeres; array CGH; SNP array; PCC; metabolic investigations in urine and blood and DNA analysis of PITX2, GREM1, FOXD3, and FOXC1 |
*Height and head circumference charts: primary microcephaly and primordial dwarfism.
†Centiles from the child growth foundation 1996/2001.