Beckwith-Wiedemann syndrome is an overgrowth disorder characterized by neonatal macrosomia, abdominal wall defects, macroglossia, renal anomalies, organomegaly, hypoglycemia, and cancer predisposition. Hepatoblastoma is the second most frequent tumor and periodic serum alpha-fetoprotein (αFP) dosage is the cornerstone of the tumor surveillance for its early detection. In this report, we describe the outstanding case of a Beckwith-Wiedemann syndrome (BWS) newborn with severe phenotype and paternal chromosome 11 uniparental disomy (UPD11) associated with a high tumor risk. Based on the clinical picture and previous reports, a close monitoring of αFP was commenced. The marker was normal immediately after birth, but rapidly raised in 20 days, leading to the diagnosis of an extremely aggressive hepatoblastoma. The latter was successfully treated with pre-surgical reductive chemotherapy, gross total mass resection, and subsequent chemotherapy. Based on this observation, the tumor surveillance routinely suggested every 3 months should be more intense and with closer time intervals in newborns with severe BWS phenotype. We suggest monitoring neonatal αFP every 20 days in such cases.

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This report emphasizes the role of the clinician in recognizing the clinical variability and the genetic heterogeneity of CL/P.

We report on a newborn boy with a bilateral cleft of the primary palate, duplicated triphalangeal thumbs, and a patent foramen ovale. During childhood he had moderate developmental delay. Brain MRI at 4 years was normal. The concurrence of non-syndromic clefts of the lip/palate (CL/P) and duplicated thumbs with triphalangeal component has, to our knowledge, not been reported so far. In our case, array-CGH analysis documented two de novo deletions (∼1.2 Mb and ∼400 Kb) of the long arm of chromosome 4, containing four genes: platelet-derived growth factor C (PDGFC), glycine receptor beta subunit (GLRB), glutamate receptor ionotropic AMPA2 (GRIA2), and F-box protein 8 gene (FBXO8). PDGFC codes for a mesenchymal cell growth factor already known to be associated with clefts of the lip. Pdgfc(-/-) mice have skeletal anomalies, and facial schisis resembling human cleft/lip palate. GRIA2 codes for a ligand-activated cation channel that mediates the fast component of postsynaptic excitatory currents in neurons, and may be linked to cognitive dysfunction. FBXO8, a gene of unknown function, is a member of the F-box gene family, among which FBXW4, within the minimal duplicated region associated with human split-hand/foot malformation type 3 (SHFM type 3). The presence of overlapping deletions in patients who do not share the same phenotype of our case suggests incomplete penetrance, and a possible effect of modifier genetic factors.

Aim: To determine the association between dental anomalies and type of facial cleft, gender, ethnicity and timing of hard palate repair surgery. Methods: This observational study comprised a total of 85 non-syndromic cleft children (mean age 9.7 ± 3.2 years) of different ethnicity (68 Caucasians, 7 Asians, 4 Africans, 5 Hispanics and 1 Indian). Sixty-four patients were affected by lip palate cleft, 11 by lip alveolus cleft and 10 by palate cleft. Sixty-one children underwent delayed palate repair at 4.3 years of age, while 21 underwent early palate periosteoplasty at 7.2 months of age. Patients were examined clinically and radiologically to assess dental anomalies. Dental cavities were registered using dmft/DMFT indexes in primary and permanent dentition, while enamel defects were evaluated only in permanent teeth using Aine index. Results: Tooth rotation and agenesis were the most common tooth anomalies affecting 59% and 42.2% of cleft patients, respectively. While a late closure of the cleft palate was associated with a higher number of rotations (P = 0.03), an early surgical correction was associated to a higher frequency of tooth agenesis (P = 0.02), number of carious lesions in primary dentition (P = 0.002) and more severe enamel defects in permanent teeth (P < 0.01). A late palate repair increased 3.5 times the likelihood of having at least one rotated tooth (P = 0.034), while decreased the odds of having agenesis by 70% (P = 0.029) compared to an early surgical repair. Conclusion: Early surgical approaches seem to have more detrimental effects on dental development in both primary and permanent dentition than late surgical protocols. Dental abnormalities in cleft patients have complex etiology combining genetic and external factors and their prevalence can also depend on timing of hard palate surgery.

A girl with oral, facial, and digital anomalies presented at birth with a large cleft palate filled by a nasopharyngeal mass and was found later to have several vertebral anomalies and mental retardation. A similar phenotype has been previously reported in a sporadic male patient [Gabrielli et al., 1994: Am J Med Genet 53:290-293], suggesting a new variant form of oral-facial-digital syndrome.

Craniofacial clefts have an incidence of 1/700 [...]

We report on an Italian boy, born to normal and nonconsanguineous parents with a prenatal diagnosis of ventriculomegaly and subependymal glial heterotopias. At birth bilateral macrostomia was diagnosed without other evident facial anomalies. Magnetic resonance imaging (MRI) showed triventricular hydrocephalus and aqueductal stenosis and confirmed the nodules of glial heterotopia. The bilateral macrostomia was surgically corrected with the vermilion square flap method and W-plasty technique and follow up MRI at 6 months showed mild increase of ventricular dilatation without signs of active hydrocephalus. The association between macrostomia and hydrocephalus has been reported only in rare cases of complex malformative syndromes but never with isolated macrostomia.