First description of frequent occurrence of supernumerary lumbar ribs and transitional vertebrae in children with Williams-Beuren syndrome.

BACKGROUND: Williams-Beuren syndrome is a rare multisystemic genetic disorder with an incidence of 1 in 7,500 live births. Because these children often have scoliosis, they undergo routine radiographic examinations of the spine. During these examinations we have found many children with supernumerary lumbar ribs arising from the first lumbar vertebra, often associated with lumbosacral transitional vertebrae. OBJECTIVE: To describe the incidence of supernumerary ribs and transitional vertebrae in children with Williams-Beuren syndrome and compare it to the incidence in a general population. Our hypothesis is that these findings are common, but they have not been described in the literature concerning Williams-Beuren syndrome. MATERIALS AND METHODS: From January 2015 to October 2021, 308 patients (138 male) with Williams-Beuren syndrome were treated at our hospital. Of these, 106 (47 male) underwent diagnostic imaging, mostly for suspected scoliosis. Panoramic radiographs of the whole spine were performed in 88 patients and radiographs of regions of the spine, chest radiographs, CT, MRI or fluoroscopy in 18 patients. We retrospectively analysed the images concerning the number of ribs and vertebrae. We correlated the frequency of lumbar ribs and transitional vertebrae in comparison to a general population as described in the literature. RESULTS: After exclusions for insufficient imaging, we analysed imaging in 91 patients. Of these, 67 patients (73.6%) had 13 ribs, of which 85% were located on both sides, 9% on the right and 6% on the left side. Of the 67 patients with supernumerary lumbar ribs, 38 (57%) also had transitional vertebrae. CONCLUSION: Supernumerary lumbar ribs arising from the first lumbar vertebra, often accompanied by lumbosacral transitional vertebrae, are common in children with Williams-Beuren syndrome.

Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene.

Patients with pyridoxine dependent epilepsy (PDE) present with early-onset seizures resistant to common anticonvulsants. According to the benefit of pyridoxine (vitamin B(6)) and recurrence of seizures on pyridoxine withdrawal, patients so far have been classified as having definite, probable, or possible PDE. Recently, PDE has been shown to be caused by a defect of alpha-amino adipic semialdehyde (AASA) dehydrogenase (antiquitin) in the cerebral lysine degradation pathway. The accumulating compound piperideine-6-carboxylic acid (P6C) was shown to inactivate pyridoxalphosphate (PLP) by a Knoevenagel condensation. Pipecolic acid (PA) and AASA are markedly elevated in urine, plasma, and cerebrospinal fluid (CSF) and thus can be used as biomarkers of the disease. We have investigated 18 patients with neonatal seizure onset, who have been classified as having definite (11), probable (four), or possible (three) PDE. All patients had elevated PA and AASA in plasma (and urine) while on treatment with individual dosages of pyridoxine. Within this cohort, molecular analysis identified 10 novel mutations (six missense mutations, one nonsense mutation, two splice site mutations) within highly conserved regions of the antiquitin gene. Seven mutations were located in exonic sequences and two in introns 7 and 17. Furthermore, a novel deletion of exon 7 was identified. Two of the 36 alleles investigated require further investigation. A known mutation (p.Glu399Gln) was found with marked prevalence, accounting for 12 out of 36 alleles (33%) within our cohort. Pyridoxine withdrawal is no longer needed to establish the diagnosis of "definite" PDE. Administration of pyridoxine in PDE may not only correct secondary PLP deficiency, but may also lead to a reduction of AASA (and P6C) as presumably toxic compounds.