The patient, a 4-year-old girl, was the second child of a healthy, nonconsanguineous couple. The family history was negative for genetic diseases, and the child was born after a normal gestation by vaginal delivery. Her birth weight was 2.600 g (5
th percentile), her length was 47 cm (10
th percentile), and her occipitofrontal circumference (OFC) was 30.5 cm (<3
rd percentile). The following features were noted at birth: a high palate, synophrys, low-set hairline, a small up-turned nose, a single transverse palmar crease, and hypertrichosis of the face and the back. No major hand malformations were detected, and an examination of the kidneys and urinary tract showed no anomalies. The phenotype was mild (total score 14) according to the clinical score suggested by Selicorni et al. [
6]. The standard karyotype was normal. A suspicion of CdLS was confirmed by molecular analysis of
NIPBL (NM_133433), which revealed a c.4920 G > A
de novo mutation. This variant has never been reported in the literature, ExaC, or the 1000 Genomes browser. The variant is considered disease-causing by prediction tools (i.e., mutation tester) with a high probability score. A perturbation of normal splicing is expected, in fact the mutation affects the last base of exon 24. Moreover, the variant was not present in the patient’s parents, confirming its pathogeneticity. A hyperechoic solid mass in the right kidney measuring approximately 3 cm at its maximum diameter was detected by renal ultrasound scan performed as part of a routine exam at the age of 2 years. The lesion lacked MRI contrast enhancement and initially thought to be benign. However, one year later, ultrasound showed that the mass had grown to a length of 5 cm. Computerized tomography (CT) characterized the lesion as a large enhanced mass protruding from the renal capsule that did not affect vessels or adipose tissue; these findings suggested that the lesion had a malignant nature. A Tru-Cut biopsy revealed non-anaplastic triphasic nephroblastoma, and the patient was treated pre-operatively according to the AIEOP-TW-2003 protocol (i.e., four courses of a regimen of vincristine and actinomycin D). Nephrectomy was then performed, followed by an additional 4 weeks of chemotherapy. At the last follow-up 19 months after treatment, the patient was healthy with no detectable disease, with hypertrophy of the contralateral kidney, 75
th percentile according to body surface area (BSA), and a normal glomerular filtration rate (128 mL/min/1.73 m
2 BSA). At that time, the patient’s weight was 11.5 kg (50
th percentile for CdLS), height 92 cm (50
th percentile for CdLS), and OFC 42 cm (50
th percentile for CdLS) [
18].