History
A 2560g female with intrauterine growth restriction was delivered vaginally at 37 weeks to a 26-year-old G3P2002 obesefemale with a history of tobacco and marijuana use in pregnancy. She had no other significant past medical history. APGARS were 8 and 8, at 1 and 5 minutes respectively.
She initially had respiratory distress and desaturations treated with oxygen therapy but was gradually weaned to room air over 9 days. She then developed apneic episodes with bradycardia and desaturations during feeding requiring low flow oxygen supplementation and was transferred to our institution for management of respiratory insufficiency and feeding difficulty.
ENT evaluation showed no evidence of subglottic stenosis or tracheomalacia, however, required low flow oxygen to maintain due to obstructive events. She continued with poor feeding, emesis and poor weight gain despite caloric fortification and speech therapy. Pantoprazole trial for reflux did not yield results. She subsequently required a Nissen fundoplication with placement of a gastrostomy tube on DOL 21 and 27kcal/oz formula with improved weight gain.
No pertinent family history.
Admission physical examination:
Vital signs: Temp: 36.8C HR: 133 RR: 46 BP: 64/37
Weight: 2460g (<3%) Length: 49cm (8.2%) Head circumference: 31cm (<3%)
Physical exam revealed a microcephalic infant with low set and posteriorly rotated ears, long/smooth philtrum, retrognathia and high-arched palate. She was comfortable on non-invasive respiratory support without signs of respiratory distress. Breath sounds were clear and equal bilaterally. Heart sounds were normal with no murmurs. Truncal hypotonia and bilateral varus talipes equinovarus noted.
Investigations:
CBC
WBC 12.1 x10-3 cells/mcL (6-18)
Hb 12.4 g/dL (10.6-16.4)
Hct 33.3% (32-50)
Platelets 436 x 10-3 cells/mcL (150-450)
Retic 1.1% (0.8-2.8)
BMP
Na 136 mmol/L (134-142)
K 5.1 mmol/L (3.5-5.6)
Cl 99 mmol/L (96-110)
CO2 29 mmol/L (20-28)
BUN 10 mg/dL (4-14)
Creatinine 0.4 mg/dL (0.2-0.4)
Glucose 89 mg/dL (70-105)
Calcium 9.5 mg/dL (8.9-10.5)
Chest Xray: normal
ECHO: small patent foramen ovale vs atrial septal defect with left to right shunt, normal biventricular function.
Renal ultrasound: Normal
Head ultrasound: Normal
Pneumogram: 1 central apnea, periodic breathing and 166 obstructive respiratory events associated with desaturations.
Video fluoroscopic swallowing study: Weakness, penetration but no aspiration.
Karyotype: Presence of extra structurally abnormal isochromosome for short arm of chromosome 18, i(18) (p10) in all metaphase cells.
Final Diagnosis:
Tetrasomy 18p
Discussion:
Tetrasomy 18p is a rare genetic abnormality caused by the presence of isochromosome 18p. Affected individuals have 4 copies of 18p. The true incidence is unknown and it affects males and females equally. Only about 40 cases have been described in literature and in most cases it is known to arise from a de novo mutation in early embryonic development. In the extremely rare presentation of a chromosomal mosaic pattern, it is thought to be inherited.
Clinical features vary widely and include neonatal feeding problems, craniofacial, skeletal and renal and muscle tone abnormalities. Craniofacial abnormalities include dolicocephaly, microcephaly, high arched palate, micrognathia, dysplastic low-set ears, ocular hypotelorism, cleft palate and gingival hypertrophy. Skeletal abnormalities include scoliosis, kyphosis, coxa, valga, clinodactyly, syndactyly. Neurologic findings include hypertonia, hyperreflexia, ankle clonus, spasticity and seizures. Renal anomalies like hydroureter, hydronephrosis, ectopic ureters and vesicoureteral reflux can also be present. This case exhibited typical craniofacial abnormalities and feeding difficulties. Additionally, she had varus talipes equinovarus bilaterally which is not frequently reported as well as respiratory insufficiency, likely a result of central hypotonia and upper airway obstruction.
