Discordant sex in monozygotic XXY/XX twins: a case report.

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.

Complex chromosomal rearrangements: origin and meiotic behavior.

BACKGROUND: Complex chromosomal rearrangements (CCRs) describe structural rearrangements, essentially translocations, involving at least three breakpoints on two or more chromosomes. Although they are rare in humans, their clinical identification is important since CCR carriers can display various phenotypes which include phenotypically normal subjects, infertile males and patients with mental retardation and/or congenital abnormalities. The rearrangement can be de novo or familial. The use of fluorescent in situ hybridization assays and molecular techniques for the characterization of CCRs have indicated that the rearrangements could be more complex than initially assumed. Accumulating data have revealed that the mechanisms underlying the genesis of CCRs remain elusive. METHODS: We performed a large PubMed search in order to summarize the current knowledge in this field and address important aspects of CCR formation and meiotic behavior, highlighting the complexity of these rearrangements at the chromosomal and genomic level. RESULTS: The review of published data indicates that the complexity of CCRs is becoming increasingly known, thanks to the application of more and more efficient molecular techniques. These approaches have allowed the precise sequence analysis of breakpoints and the identification of insertions, deletions, inversions and recombination events. New models have been proposed for the formation of CCRs, based on replication-based mechanisms and specific sequence elements. Their meiotic behavior has been discussed in the light of these new molecular data. CONCLUSIONS: Despite the increasing understanding of the mechanisms involved in their genesis, CCRs arise as unique, complex events for which the genetic and reproductive counseling of carriers remains a challenge.

Severe slipped capital femoral epiphysis: the Dunn's operation.

INTRODUCTION: Severe slipped capital femoral epiphysis inevitably results into arthritis, making surgical recovery of normal anatomy an attractive objective. This can be achieved by the procedure described by Dunn. However, all published studies report a risk of avascular necrosis. MATERIAL AND METHODS: The present series assembles 25 adolescent cases aged 10 to 15 years. There were 16 cases of chronic pure displacement with several months' evolution, including nine exacerbated by an acute accident. In all cases, epiphyseal slippage was severe, between 60 degrees and 90 degrees. Postoperative traction was systematic, for 15 to 21 days. As of 1979, bone scan was prescribed 2 weeks postsurgery to study femoral head vascularization. RESULTS: Reduction was anatomic, except in two cases in which the epiphysis was fixed, respectively in caput valgum and in 15 degrees varus. There were 15 good results, with clinically and radiologically normal hips, but also 10 immediate or late complications: i.e., a complications rate of 40%. The eight immediate complications (32%) comprised four necroses (16%), two of which rapidly evolved into arthritis, three chondrolyses, which all evolved into arthritis, and one mechanical complication. At less than 10 years' FU, two arthrodeses and three hip replacements were required. At long-term FU, there were two further late deteriorations, despite initial favorable clinical and X-ray outcomes. DISCUSSION: In theory, the procedure described by Dunn limits the vascular risk of the displacement correction. It does, however, involve certain tricky technical points: trochanterotomy may be excessive or insufficient; posterior cervical periosteal detachment may be aggressive; and the periosteum may be too tight during the reduction. In all series studying Dunn's operation, such risk of necrotic complication is reported, at rates up to 17%. The present series had a 16% rate of necrosis which, associated with chondrolysis, caused immediate loss of joint function--unacceptable, in our view, in adolescent patients. A direct approach to the displacement, after arthrotomy, with associated anterior cuneiform neck resection, corrects the slippage while avoiding the risky first two steps of Dunn's procedure, and is our current approach of choice.

[Proximal femoral resection in nonambulatory multiply handicapped child]. / Résection fémorale supérieure chez l'enfant polyhandicapé grabataire.

INTRODUCTION: Hip dislocation in nonambulatory multiply handicapped children (particularly in cerebral palsy [CP]) is a common and severe problem involving painful transportation and uneasy positioning, usually resulting from major anatomical osteoarticular and soft tissue disorders. Therefore, proximal femoral resection is seen as a salvage procedure whose primary purpose is to provide children and their caregivers with better comfort during activities of daily living thus allowing improved sitting tolerance in the wheelchair and painless nursing care. MATERIALS AND METHODS: A series of 21 proximal femoral resections performed on 16 patients with a mean age at surgery of 12 years, and a follow-up period of 21 years (from 1984 to 2005) were retrospectively reviewed. All patients suffered from painful dislocation of the hip. Sixteen of the hips (76%) had been managed previously with bony and soft tissue surgery. Femoral resection was performed in the basicervical region in eight hips and distal to the lesser trochanter in 13 hips. RESULTS: At a mean follow-up of five years and eight months, 18 of the 21 painful hips reported to be painless (86%). All preoperative stiffness and deformity of the hip joints was corrected, resulting in floppy, mobile hips with an increased range of motion after surgery. Femoral stump, regarding the acetabulum was above in three hips, at the same level in 18 and never below. The proximal end of the femoral shaft could often been palpated but did not reveal any skin irritation. The formation of heterotopic bone was discernible in five hips (24%). However, it did not affect the functional outcomes. DISCUSSION: Soft-tissue releases combined with femoral and pelvic osteotomies have reported poor results with regard to their long-term inefficacy in children. The outcomes of our series support these findings, since surgical procedures had been performed previously in 76% of the hips. Therefore, we believe that proximal femoral resection is a promising and reliable surgical treatment option to address such failures, in case of severe and painful deformities of the hip. The success of our series corroborates Widemann, Mc Carthy and Abu-Rajab encouraging results on proximal femoral resection. Postoperatively, we advise placement of a hip spica cast immobilization with a soft cotton lining to prevent pressure sores from developing. This surgical procedure seems to be an appropriate management in nonambulatory multiply handicapped children reporting more promising results than other surgical treatment options such as rotational osteotomy, arthrodesis or even arthroplasty.

[Virilizing ovarian tumors in the menopausal patient]. / Tumeurs virilisantes de l'ovaire chez la femme ménopausée.

Virilizing ovarian tumors are rare and can occur at any age. In postmenopausal women, they commonly present with signs of masculinization. These tumors should be suspected in any patient with virilization and high testosterone levels (>1ng/mL). Tumor localization is sometimes difficult. These tumors are usually benign; surgical resection is the accepted treatment. Masculinizing consequences of hormonal secretions may be managed by cosmetologic treatments which should not be overlooked.

[Multiple myxomata: about one case]. / Myxomes multiples: à propos d'un cas.

Among the primitive cardiac tumours, myxoma is the most common. This benign tumour is sometimes described in the context of Carney's syndrome, in which cardiac myxoma, cutaneous myxoma, lentigo and pigmentary nevus cutaneous lesions, endocrine disorders, and testicular, thyroid and hypophyseal tumours are associated. The cardiac myxomata observed are multiple, recurrent, and involve the four cardiac chambers, with a peak incidence at 25 years of age. These observations may exist in a familial context, linked to an autosomal dominant genetic factor, localized on the 17q2 chromosome with polymorphism of the PRKAR1a gene. As in the case of sporadic myxoma, rapid surgical treatment with cardio-pulmonary bypass is indicated, bearing in mind the increased risk of thromboembolic phenomena and sudden death from valvular encroachment. We report a case of bi-atrial myxoma observed in the context of Carney's syndrome.

Breakpoint characterization: a new approach for segregation analysis of paracentric inversion in human sperm.

Paracentric inversions (PAI) are structural chromosomal rearrangements generally considered to be harmless. Nevertheless, cases of viable recombinants have been reported, indicating the interest of studying the meiotic behaviour of these chromosomal abnormalities. To date, the few studies reported have been performed using either the human-hamster fertilization system or fluorescence in situ hybridization with centromeric or telomeric DNA probes. In order to improve the assessment of meiotic segregation in PAI, we present a new strategy based on the use of bacterial artificial chromosome (BAC) probes which allow a precise localization of chromosome breakpoints and the identification of all meiotic products in human sperm. Sperm samples from carriers of an inv(5) and an inv(14) were used to test this new high-resolution procedure.

[Osteochondritis dissecans of the femoral condyles: report of 892 cases]. / L'ostéochondrite disséquante des condyles fémoraux.

PURPOSE OF THE STUDY: Osteochondritis rarely involves the femoral condyles. Discovery in this localization raises several questions concerning the nature of the articular cartilage, the potential for spontaneous healing, and, in the event of a free fragment, the outcome after its loss or repair. MATERIAL AND METHODS: This multicentric study included 892 pediatric and adult cases, the cutoff between two series being defined by fusion of the inferior growth plate. We excluded medical or surgical osteochondritis, cases involving the patella, osteochondral fractures, juvenile polyosteochondrosis, adult osteonecrosis, and osteochondritis beginning after the age of 50 years. RESULTS: Mean age at diagnosis was 16.5 years. Mean age at treatment onset was 22 years. Pain was the predominant symptom. 80% of cases were unilateral and 70% involved the medial condyle. The anatomic lesions were different in adults, showing more advanced degradation. At diagnosis, Bedouelle stages Ia and IIb constituted 80% of the cases observed among children while in adults, 66% were Bedouelle stages IIb to IV. Outcome was very good for the majority of children with Hughston clinical stage 4 while half of the x-rays were Hughston stage 3 and 4. There were thus a large percentage of children with abnormal xrays whose disease history was not yet terminated. In the adult series, the percentages of Hughston 3 and 4 was about the same as clinically. The x-rays were rarely perfectly normal since half of the clinical stage 3 patients were noted in stage 4. An abnormal x-ray with a very good clinical presentation was observed in a very large proportion of patients. DISCUSSION: It is difficult to interpret the plain x-ray and identify patients with a potentially unfavorable prognosis. We defined three radiographic classes: defect, nodule and empty notch. The Bedouelle classification uses information from all available explorations, particularly MRI and arthroscopy. Numerous therapeutic methods are used. Interruption of sports activities is the first intention treatment for children. Data in the literature and the findings of this symposium do not demonstrate any beneficial effect of immobilization on healing compared with simple abstention from sports activities. Transchondral perforation is a simple operation with low morbidity. In 85% of cases, it was used for lesions with an intact joint cartilage considered stable in 96% of cases. Healing was achieved in six months for 48% if the growth plate had not fused. The fragment was fixed in 43% of the cases with a loose cartilage fragment. Outcome was fair but degraded with the state of the joint cartilage and thus the stability of the fragment. Fixation must stabilize the fragment but not prevent further consolidation via osteogenesis. This is why deep perforations are drilled beyond the ossified area and additional osteochondral grafts are used. The Wagner operation gives less satisfactory results than more complicated procedures. Removal of a sequestrum is a simple, minimally invasive procedure with an uneventful postoperative period, but in the long term it favors osteoarthritic degradation, especially when performed in adults. Mosaic grafts give good mid term results. Morbidity is low especially if the grafts are harvested above the notch. The question of chondrolysis around the grafts was beyond the scope of this study. Chondrocyte grafting is difficult to accomplish and is expensive. The mid term results are good for large lesions. Osteotomy is logical only in the event of early stage osteoarthritic degradation. DECISION ALGORITHM IN CHILDREN AND ADOLESCENTS: If the plain x-ray reveals a defect (class I), simple interruption of sports activities should be proposed. Two situations can then develop. First, in a certain number of patients, the pain disappears as the defective zone ossifies progressively. Complete cure is frequent before the age of 12 years. In the second situation, the knee remains painful and the x-ray does not change or worsens to a class II nodular formation. In this case an MRI must be obtained to determine whether the joint cartilage is normal. There are two possibilities. First, the osteochondral fragment is viable and most probably will become completely re-integrated, particularly if the lesion is far from the growth plate. Necrosis is the other possibility. Transchondral perforations are needed in this case. If on the contrary the cartilage is altered, there is little hope for spontaneous cure. Arthroscopy may be needed to complete the exploration. Fragments, especially if there is a large surface area, must be fixed. Perforations to favor revascularization are certainly useful here. In the last situation (class III), the fragment wobbles on a thin attachment or has already fallen into the joint space. This is the type of problem generally observed in adults. The decision algorithm in adults is the same as in children for the rare nodular aspects (class II). There could be a discussion between transcartilage perforation and fixation. If there are a large number of fragments, fixation may not be fully successful and the lesion might be considered class III. For class III lesions, three operations can be used: removal of the sequestrum, mosaic bone-cartilage grafts, or autologous chondrocyte grafts. At the same follow-up, mosaic grafts give better results than excision of sequestra. It may be useful to remove sequestra in a limited number of situations: if there is just a small area of osteochondritis, the lesion is old and partially healed, or the zone is non weight-bearing. For other lesions, we favor mosaic grafts. We still do not have enough follow-up to assess the long-term outcome with these mosaic grafts, but simple excision clearly favors osteoarthritic degradation. Can chondrocytes grafts be compared with mosaic grafts? Chondrocyte grafts have been used for very large lesions and have given results similar to mosaic grafts. It might also be possible to combine fixation of a loose fragment and a mosaic graft. LESSONS FROM THIS STUDY: 1) The prognosis of osteochondritis is better before than after fusion of the growth plate but the lesion does not always heal in children. 2) Presence of osteochondritis requires complementary anatomic and functional exploration to determine the stability and the vitality of the fragment. 3) Attention must be taken to perform transchondral perforations early enough, particularly in children. 4) Screw fixation is not always sufficient. The trophicity of the fragment and its blood supply must be improved. 5) Mosaic grafts are preferable to excision of the fragment. 6) Chondrocyte grafts will be more widely used in the future.

Multicolor PRINS and multicolor PNA.

Both PRimed IN Situ (PRINS) and Peptide Nucleic Acid (PNA) technologies have emerged as research techniques, but they have quickly evolved to applications in biological diagnosis assays. The two procedures now constitute efficient alternatives to the conventional fluorescence in situ hybridization (FISH) procedure for in situ chromosome identification and aneuploidy detection. They present several advantages (specificity, speed, discriminating ability) that make them very attractive for a number of cytogenetic purposes. Multicolor PRINS and PNA protocols have been described for the specific identification of human chromosomes. Various applications have already been developed in human genetics and new adaptations are ongoing.

Rare Robertsonian translocations and meiotic behaviour: sperm FISH analysis of t(13;15) and t(14;15) translocations: a case report.

t(13;15) and t(14;15) are two rare Robertsonian translocations. Meiotic segregation was studied in four males heterozygous for the rare Robertsonian translocations t(13;15) and t(14;15). Both locus-specific probes (LSPs) and whole chromosome painting (WCP) probes, specific to chromosomes 13, 14 and 15, were used in this study. The number of spermatozoa scored for each carrier ranged from 891 to 5000. The frequencies of normal and balanced sperm resulting from the alternate mode of segregation ranged from 77.6 to 92.8%, confirming the prevalence of alternate segregation over other segregation modes in all Robertsonian translocations. The incidences of unbalanced complements ranged from 6.7 to 20.4%, with a significant excess of disomy rates over the complementary frequencies of nullisomy. This variability might reflect differences in the location of breakpoints in translocated chromosomes, leading to the variable production of unbalanced gametes and the variable alterations of semen parameters in Robertsonian translocation carriers.

Meiotic segregation of rare Robertsonian translocations: sperm analysis of three t(14q;22q) cases.

BACKGROUND: The t(14;22) remains one of the rare Robertsonian translocations observed in human, with an occurrence estimated at 1.2%. Three cases of rare Robertsonian translocation t(14;22) were investigated for meiotic segregation in sperm samples from male carriers using the fluorescent in situ hybridization (FISH) procedure. The three carriers included two men with an abnormal semen analysis and one with normal semen parameters. METHODS: Both locus-specific probes and whole-chromosome painting probes, specific for chromosomes 14 and 22, were used in this study. The number of spermatozoa scored for each probe set ranged from 3279 to 10,024. RESULTS: In the three carriers, similar frequencies, ranging from 78.53 to 81.76%, were found for normal and balanced spermatozoa resulting from alternate segregation. The total proportion of unbalanced spermatozoa resulting from adjacent modes of segregation ranged from 17.59 to 20.94%. CONCLUSION: This finding confirmed the predominance of alternate segregation over other segregation types in all Robertsonian translocations and indicates a higher production of imbalances in the t(14;22) than in most of the Robertsonian translocations previously analysed. This could be related to the variable location of breakpoints in Robertsonian translocations. This breakpoint diversity could also play a role in the differences in reproductive status observed in male carriers of Robertsonian translocations.

[Management of Lagrange and Rigault stage IV extension type supracondylar fracture of the humerus in children]. / Prise en charge des fractures supracondyliennes en extension stade IV de Lagrange et Rigault.

PURPOSE OF THE STUDY: Lagrange and Rigault stage IV extension type supracondylar fracture of the humerus (Gartland and Wilkins type III) involves major displacement, making treatment difficult. Several therapeutic methods have been described but indications vary considerably between teams. We conducted a retrospective analysis in order to evaluate the results of different methods, identify the most adapted technique, and detail the conditions necessary for good results with the collar and cuff immobilization method described by Blount. MATERIAL AND METHODS: Forty-four children (30 boys and 14 girls), mean age seven years six months, were treated between January 1990 and December 2001. The collar and cuff immobilization technique was used for sixteen children (including four who underwent open revision for early secondary displacement), percutaneous pinning for two, and open crossed pinning for thirty (including four who developed secondary displacement after collar and cuff immobilization). One out of two collar and cuff treatments was instituted within six hours of injury. The four secondary displacements after collar and cuff immobilization treatment occurred after fracture reduction more than six hours after injury. The proportion of open reductions increased with longer delay to reduction after injury. Mean immobilization was three and a half weeks. The Flynn criteria were used to assess outcome at mean seven years eight months follow-up. RESULTS: Outcome was satisfactory in all children treated with definitive collar and cuff immobilization and by percutaneous pinning; the rate was 97% after open procedures (persistent sequelae of radial palsy in one child). DISCUSSION: Early treatment before six hours increased the chances of success with the collar and cuff method which remains the technique of choice for Lagrange and Rigault stage IV extension type supracondylar fractures. In the event of failure or complications, other classical methods should be discussed, including percutaneous pinning or direct access for open osteosynthesis.

[Percutaneous rotational osteoclasis in management of congenital radio-ulnar synostosis]. / Ostéotomies percutanées de dérotation de l'avant-bras dans les synostoses radio-ulnaires congénitales de l'enfant.

PURPOSE OF THE STUDY: Congenital radio-ulnar synostosis blocks the wrist in a position of more or less pronounced pronation. The degree of pronation and possible bilateral involvement can compromise upper limb function. We propose percutaneous osteoclasis of the antebrachial skeleton to remedy this situation PATIENTS AND METHODS: We performed 12 percutaneous rotation osteoclasis procedures. The objective was to weaken the metaphysodiaphyseal cortical periosteum of one or both of the forearm bones by intermittent perforations. This enabled derotation of the wrist which was maintained for six to eight weeks in a brachiopalmar cast. RESULTS: Mean correction of pronation was 51 degrees. There were no cases of vascular or nervous complications and healing was uneventful. The esthetic outcome was very satisfactory. DISCUSSION: Surgery is not indicated for all cases of synostosis. We retain for surgery patients presenting pronation at 60 degrees or more. At this degree of pronation, function is greatly compromised in adolescence, particularly if there is a bilateral involvement. Compared with other techniques, percutaneous osteoclasis is a simple safe and reliable technique. Reoperation is not required to remove material. The procedure is easier in young children, preferably at the age of 3 to 7 years, before the development of a functional handicap.

[Capsular shift for voluntary dislocation of the shoulder: results in children]. / Capsulorraphie dans les instabilités volontaires de l'épaule: résultats chez l'enfant et l'adolescent.

PURPOSE OF THE STUDY: Chronic shoulder instability is uncommon in patients with an immature skeleton. Some of these pediatric patients can produce their dislocation voluntarily raising the question of the traumatic or constitutional nature of the condition as well as its direction and tolerance. We report our experience with 29 patients. MATERIAL AND METHOD: Over a period of 28 years, 29 children aged 5 to 15 years were treated for voluntary shoulder dislocation. The dislocation was painful and poorly tolerated in 19, affecting daily life and sports activities. Posterior dislocation was observed in 15 patients and anterior dislocation in 4, but the direction was not always easy to establish, particularly in children with ligament laxity; multiple directions were not uncommon. Rehabilitation for at least eight months did not relieve pain in 11 patients who had a sensation of a blocked, unreliable shoulder which could not be controlled voluntarily. Posterior capsulorrhaphy was performed in 8 patients and anterior capsulorrhaphy in 3. RESULTS: Mean follow-up was 8 years. At last follow-up, all shoulders were stable and shoulder motion was normal with no loss of function. More than half of the children had resumed sports activities. Capsulorrhaphy was proposed when the pre-operative explorations did not reveal any bone or rim anomaly. The only preoperative finding in the operated patients was increased capsule volume, particularly in the inferior portion. Intraoperatively, ulceration of the humeral cartilage was found in two patients. Anatomic reconstruction of the capsuloligamentary structures enabled recovery of passive stability and active stability of the scapulohumeral joint, preventing further voluntary dislocation.

Ultra-rapid multicolor PRINS protocol for chromosome detection in human sperm.

We report a new multicolor PRINS procedure for chromosome identification on human sperm. Based on the direct in-situ mixing of the colors of the fluorochromes (FITC, TRITC, Cascade Blue) incorporated in sequential PRINS reactions, this method facilitates rapid distinct labeling of 3 or 4 chromosomes. Each PRINS reaction consists of a unique 4 minute step for annealing and elongation. The method was successfully tested on lymphocytes and spermatozoa. Estimates of disomy were performed for chromosomes 7, 9 and 16 on sperm samples from 2 healthy donors. There was no significant difference between the disomy rates obtained with the conventional two-color PRINS technique and this new three-color procedure. By simplifying the multicolor PRINS protocol, this new protocol should facilitate the use and adaptation of PRINS to various cytogenetic applications.

[Primary thyroid lymphoma: report of 8 cases]. / Lymphome malin primitif de la thyroïde: à propos de huit cas.

PURPOSE: Primary thyroid lymphoma (PTL) is a rare disease. Few patients are reported in the literature. We report eight new cases of PTL with long-term follow-up. RESULTS: The clinical presentation was usually an enlarging neck mass squeezing surrounding structures. The diagnosis was established after thyroidectomy with histopathologic and immunohistochemical studies. Histology showed infiltrates of chronic lymphocytic thyroiditis in all cases. Three patients had thyroid lymphoma arising from mucosa-associated lymphoid tissue. One patient died postoperatively. The other seven were treated with combined chemotherapy and radiotherapy. They were still in remission after a 6-year follow-up. CONCLUSION: Diagnosis of PTL should be suspected when there is a recent thyroid enlargement. Surgery associated with chemotherapy and radiation gave good results in our study with long-term follow-up, though surgery was not always recommended in previous reports.

Neurological presentation of three patients with 22q11 deletion (CATCH 22 syndrome).

Chromosome 22q11 deletion (CATCH 22 syndrome or velocardiofacial syndrome) is one of the most frequent chromosomal syndromes. Neurological features other than cognitive disorders are probably the least-described part of the expanding phenotype of the 22q11 deletion. We report the neurological features of three unrelated children with a de novo deletion: one patient with an autistic disorder, a second patient with hypocalcaemic neonatal seizures and unusual persistent epileptic focus at electroencephalographic follow-up, and a third patient with atypical absence epilepsy. These observations enlarge the clinical and neurological spectrum of the 22q11 deletion. Awareness of such cases is necessary, and a diagnosis of the 22q11 deletion should be suspected in children with common neurological features associated with severe or mild dysmorphism. Diagnosis of the 22q11 deletion should be confirmed by fluorescence in situ hybridization analysis associated with standard chromosomal analysis.