16p13.11 microduplication in 45 new patients: refined clinical significance and genotype-phenotype correlations.

BACKGROUND: The clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype-phenotype correlations to improve genetic counselling and patients' medical care. METHODS: We retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents. RESULTS: Clinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype-phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype. CONCLUSION: Our study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.

Outcome of alimentary tract duplications operated on by minimally invasive surgery: a retrospective multicenter study by the GECI (Groupe d'Etude en Coeliochirurgie Infantile).

BACKGROUND: Alimentary tract duplications (ATD) are a rare cause of intestinal obstruction in childhood. There are many case reports but few series about laparoscopy or thoracoscopy for ATD. The aim of our study was to report the outcome of minimally invasive surgery (MIS) for ATD. METHODS: This was a retrospective multicenter study from the GECI (Groupe d'Etude en Coeliochirurgie Infantile). We reviewed the charts of 114 patients operated on by MIS for ATD from 1994 to 2009. RESULTS: Sixty-two patients (54 %) had a prenatal diagnosis. Forty-nine patients (43 %) were symptomatic before surgery: 33 of those patients (63 %) with postnatal diagnosis compared to 16 (25 %) with prenatal diagnosis (P < 0.01). In this last group, the median age at onset of symptoms was 16 days (range = 0-972). One hundred and two patients had laparoscopy (esophageal to rectal duplications) and 12 patients had thoracoscopy for esophageal duplications. The mean operative time was 90 min (range = 82-98). There were 32 (28 %) resection anastomoses, 55 (48 %) enucleations, and 27 (24 %) unroofings. The conversion rate was 32 %, and in a multivariate analysis, it was significantly higher, up to 41 % for patients weighing <10 kg (P < 0.01). Ten patients (8 %) had unintentional perioperative opening of the digestive tract during the dissection. Eight patients had nine postoperative complications, including six small bowel obstructions. The median length of hospital stay was 4 days (range = 1-21) without conversion and 6 days (range = 1-27) with conversion (P = 0.01). The median follow-up was 3 months (range = 1-120). Eighteen of the 27 patients who underwent partial surgery had an ultrasound examination during follow-up. Five (18 %) of them had macroscopic residue. CONCLUSION: This study showed that MIS for ATD is feasible with a low rate of complications. Patients with prenatal diagnosis should have prompt surgery to prevent symptoms, despite a high rate of conversion in small infants.

Laparoscopic gastropexy for the treatment of gastric volvulus associated with wandering spleen.

A 2.5-year-old boy was referred to the emergency room for a sudden onset of diffuse and increasing abdominal pain with lethargy, abdominal distension, and vomiting, all in the past 24 hours. A plain abdominal X-ray showed gastric distension. Two liters of gastric contents were evacuated by suction. The abdominal sonogram showed an unusual position of the spleen in the left-lower quadrant, with no splenic ischemia. The diagnosis of gastric volvulus associated with a wandering spleen was then evoked. Laparoscopic exploration revealed a nonischemic spleen, absence of normal supporting ligaments for the spleen, and gastric distension with flaccid gastric walls. The spleen was then easily moved in the left-under quadrant. A parietal peritoneal posterolateral incision was made, opposite the large gastric curve, up to the diaphragm (7 cm). This delimitated a sharp demarcation zone between the two edges of the incised peritoneum. The stomach was fixed to the peritoneal incision, covering and anchoring the spleen in a good position. Recovery was uneventful, and an abdominal sonogram performed 4 years after the surgery shows a viable spleen in its correct location. The rarity of gastric volvulus associated with a wandering spleen and its fast clinical improvement with medical treatment often delays the diagnosis and the surgical treatment. Laparoscopy in this case has a dual relevance: diagnosis and therapeutic management (splenectomy or gastropexy). Laparoscopic gastropexy for the treatment of gastric volvulus associated with a wandering spleen is an easy procedure and combines the advantages of all the surgical techniques previously described.

Cleft palate and bilateral congenital cataract: a familial observation: a new syndrome?

We report a family with a rare association of congenital bilateral cataract and cleft palate that has not to our knowledge been previously reported. The lineage has unveiled abnormalities over four generations affecting 21 people with congenital bilateral cataract, with or without cleft palate. The transmission seems autosomal dominant. Four brothers and sisters presented with this defect, and a fifth sister is healthy. The mother has facial dimorphism, congenital bilateral cataract, submucous cleft palate, clinodactyly, and scoliosis. The propositus' karyotype was normal. Array comparative genomic hybridisation (CGH) analysis showed an interstitial amplification in Xp21.1, found in the mother, in all the affected siblings but one, and in the healthy girl. Thisl association is not rare and has been reported in over 50 syndromes but rarely in familial observations. Based on the genetic-clinical discordance we wonder about the deleterious impact of the Xp21.1 amplification that might be a copy number polymorphism.