Developmental outcome of children with Robin sequence: How does the question arise?

Robin sequence (RS) is a heterogeneous congenital condition characterized by retrognathia, glossoptosis, upper airway obstruction, and very often, posterior U-shape cleft palate. Half the children with RS have an underlying syndrome, either identified (syndromic RS) or not (RS+). Long-term intellectual developmental outcome first depends on the underlying diagnosis and is often poor in syndromic cases. On the contrary, the rare studies that analysed the long-term developmental outcome of children with isolated RS who received effective treatment of their respiratory and feeding difficulties early in life, showed intellectual and academic results close to or within the normal range. Speech outcome in RS is often delayed with phonation disorders. Speech difficulties depend on intellectual level, hearing and velar function after palate repair. It affects most children with RS and deserves active monitoring and care.

The use of three-dimensional reconstructions of CT scans to evaluate anomalies of hyoid bone in Pierre Robin sequence: A retrospective study.

AIM: The aim of the study was to investigate hyoid bone anomalies in patients with Pierre Robin sequence (PRS) compared to the control group, using computed tomography (CT) examination and three-dimensional reconstruction of the hyoid bone and mandible. METHODS: A retrospective study was performed of patients between birth and 12 months old with isolated PRS (i-PRS) and syndromic PRS (ni-PRS), who had undergone CT examination, and whose results were compared to the control group of the same age. DICOM data was processed to highlight bone tissue. The mandible and hyoid bones were the main targets of the three-dimensional reconstruction. The study outcomes were the analysis of hyoid bone ossification, volume, and position (distance between hyoid and mandibular symphysis). Univariate and multivariate statistical analyses were performed with α=0.05 as level of significance. RESULTS: The study sample included 29 i-PRS and 21 ni-PRS patients, while 43 infants in the control group. Hyoid ossification was present in 26/50 (52%) PRS patients (14 i-PRS; 12 ni-PRS) but in 31/43 controls (72%). Statistical analysis showed that absence of hyoid ossification was significantly associated with the diagnosis of PRS (P<0.05). Only ni-PRS patients showed a significant reduction of the distance between hyoid and mandible compared to the control group (P<0.001). Hyoid volume was significantly lower only in the ni-PRS group than in controls (P<0.001). CONCLUSION: I-PRS and ni-PRS patients differ both etiologically and clinically. Ni-PRS patients confirmed their worst clinical condition than i-PRS with severe anomalies of hyoid development, helping for their ontogeny classification.

Pierre Robin sequence: A comprehensive narrative review of the literature over time.

Pierre Robin syndrome (PRS) is characterized of a triad of clinical signs: micrognathia, glossoptosis and obstruction of the upper airways frequently associated with palatal cleft. It is a heterogenic pathological entity and it can be found as isolated disease (nsPRS) or in association with other syndromes (sPRS), with more pronounced symptoms and systemic involvement. This review aims to summarize the principal features of PRS, analysing the different aspects of the disease. Epidemiological data highlight incidence, severity and mortality of PRS; pathophysiological mechanism reports the etiology and pathogenesis of the disease distinguishing between isolated and syndromic form. Because of the clinical importance of PRS, it's fundamental to describe the features of the Robin sequence to clearly define its primary and secondary clinical signs useful to diagnosis. A complete evaluation of the syndrome allows choosing the most appropriate therapeutic treatment, opting for conservative or surgical management, in order to improve the quality of life of the patient.

[Accidental mercury poisoning in a 12-year-old girl]. / Intoxication accidentelle au mercure chez l'enfant.

INTRODUCTION: Exposure to metallic mercury can cause severe accidental intoxications in children, whose clinical symptoms can vary depending on the route of administration, the dose, as well as the time and duration of the exposure. It has become unusual in France, yet it must be considered when taking a patient's medical history in cases of multisystemic involvement without a clear explanation. CLINICAL CASE: We report the case of a 12-year-old patient hospitalized because of a cough, poor general condition, chills, night sweats, psychomotor retardation, and skin lesions that had been developing for several weeks. The initial clinical examination also revealed sinus tachycardia, arterial hypertension, and abolition of osteotendinous reflexes. Complementary examination results were normal apart from a glomerular proteinuria without renal failure. When interviewing the mother, she reported that the child had played with mercury balls 3 months earlier. The suspicion of poisoning was confirmed by blood and urine analysis as well as renal biopsy showing an aspect of membranous glomerulonephritis with IgG and C3 depositions. An intoxication via a transdermal route being unlikely on healthy skin, the Regional Health Agency's survey concluded that chronic intoxication had occurred by inhalation of the mercury spread on the floor at the time of the exposure, which was then vacuum cleaned and released again by the contaminated vacuum cleaner. The patient's outcome was favorable within a few weeks after initiating DMSA chelation therapy. CONCLUSION: Mercury poisoning should be considered in cases of a multisystemic disorder without clear explanation, in order to intervene quickly and thus prevent irreversible renal and neurological consequences.

Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens.

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.

Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form.

Keratitis-ichthyosis-deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin.

[Acute poststreptoccocal chorea: an atypical postoperative reaction following cardiac surgery for mitral valvulopathy]. / Chorée aiguë post-streptococcique : une étrange réaction après chirurgie d'une insuffisance mitrale rhumatismale.

We report on a 12-year-old patient from Congo who presented acute chorea following cardiac surgery for poststreptococcal mitral valvulopathy. She showed severe and asymmetrical chorea, associated with motor impersistence and agitation. Biological investigations disclosed inflammatory signs and brain MRI was normal. Due to the negative results of the biological and morphological investigations, the diagnosis of Sydenham chorea was suspected. High doses of oral steroids resulted in a dramatic improvement of the chorea as well as the behavior disturbance within 1 month. Sydenham chorea is not an unusual complication of rheumatic fever. Usually, patients develop chorea a few weeks after beta-hemolytic streptococcal pharyngitis. Details on its pathophysiology remain to be determined. Our case highlights its possible onset in the postoperative period if alternative etiologies of infantile chorea have been excluded.

The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study.

This study aimed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride (6R-tetrahydrobiopterin or 6R-BH4) 10 mg/kg per day in patients with phenylketonuria (PKU), who have elevated blood phenylalanine (Phe) levels, and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level. Eligible patients were aged > or = 8 years, had blood Phe levels > or = 450 micromol/L and were not adhering to a Phe-restricted diet. Suitable patients were identified by a > or = 30% reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment. The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level (< 600, 600 to < 900, 900 to < 1200 and > or = 1200 micromol/L). In total, 485/490 patients completed the study and 20% (96/485) were identified as patients who would respond to sapropterin dihydrochloride. A reduction in Phe level was observed in all subgroups, although response was greater in patients with lower baseline Phe levels. Wide variability in response was seen across all baseline Phe subgroups. The majority of adverse events were mild and all resolved without complications. Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested. Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride cannot be predicted by baseline Phe level.

[Neonatal subcutaneous fat necrosis with hypercalcemia: efficiency of a low dose of corticosteroids]. / Cytostéatonécrose néonatale compliquée d'une hypercalcémie symptomatique: efficacité des corticoïdes à faible dose.

We report the case of a newborn with macrosomia, extensive subcutaneous fat necrosis and symptomatic hypercalcemia. Low doses of prednisone were efficient, while dietary intervention, hyperhydratation and furosemide were not. Treatment of hypercalcemia in this specific neonatal condition are discussed.

[Afebrile seizures in gastroenteritis: a Japanese peculiarity]. / Convulsions sans fièvre et gastroentérite aiguë: une spécialité japonaise.

Febrile seizures appearing during acute gastroenteritis have been described in japanese populations. These convulsions are not related to clinical signs of dehydration or electrolyte disorder. This entity was called CwG, benign Convulsions with mild Gastroenteritis. We report the case of a 19 month-old japanese boy who presented with a CwG. We described the characteristic clinical features of this entity and we reviewed the cases reported in literature. The evolution of the CwG is always simple without relapse or side effects. Better understanding will help pediatricians make more accurate diagnosis and avoid treatment even though initial signs might be severe.

CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development.

CONTEXT: CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities, and/or hearing loss defect) syndrome consists of a combination of congenital malformations including genital hypoplasia and retarded growth. OBJECTIVE: The objective of the study was to study gonadotropic axis function and growth parameters in CHARGE syndrome. DESIGN: This was a retrospective study. PATIENTS: The study included 32 children with CHARGE syndrome. RESULTS: Nineteen of 20 affected boys had micropenis and/or cryptorchidism, consistent with hypogonadotropic hypogonadism during fetal life. None of the boys was of pubertal age. Seven of nine boys tested before the age of 5 months during the neonatal peak period had extremely low testosterone levels. LH response to GnRH stimulation was variable during the first year of life and not correlated with existing clinical abnormalities. None of the girls over the age of 12 yr (n = 7) had begun puberty spontaneously, and a lack of response to GnRH stimulation was documented in five of them. Olfactory evaluation (n = 10) and magnetic resonance imaging (n = 18) of the forebrain revealed defective sense of smell and abnormal olfactory bulbs in all cases. Cardiorespiratory and nutritional problems were corrected, but the mean height of the 25 children who had reached 5 yr of age was -2 +/- 0.2 sd score. Height was not correlated with birth length or body mass index. GH deficiency was diagnosed in only three children. CONCLUSION: These findings suggest that CHARGE syndrome includes the main features of Kallmann syndrome, which is defined by hypogonadotropic hypogonadism combined with a defective sense of smell and abnormal olfactory bulb development. This forebrain abnormality, if confirmed in a larger group of patients, could serve as a major new criterion for the diagnosis of CHARGE syndrome.

[Infantile rumination]. / Mérycisme infantile.

Infantile rumination can be defined as self-induced regurgitation of previously swallowed food. Because it can lead to potential somatic complications and because it implies dysfunctional mother-child bonding, both a pediatric and psychiatric approach is needed. The treatment must be somatic (nutritional) and psychological (intensive nursing, mother-baby psychotherapy). Two case studies illustrate this rare but impressive picture.

[Management of phenylketonuria and hyperphenylalaninemia: the French guidelines]. / Consensus national sur la prise en charge des enfants dépistés avec une hyperphénylalaninémie.

Phenylketonuria (PKU) is an inherited metabolic disease affecting about one birth out of 15 000. From 1978, a national systematic neonatal screening was set up in France with a regional organisation. French rational and guidelines have been established by the national PKU group with the collaboration of all the physicians responsible for the regional centres. These guidelines specify the minimal diagnosis procedures leading to an optimal treatment of all patients. A low-phenylalanine diet must be started as soon as possible in the neonatal period for all newborns whose phenylalanine levels are above 10 mg/dl. The dietary control must keep the phenylalanine plasma levels between 2 and 5 mg/dl until 10 years of age. After this age, several data argue for a progressive and controlled relaxation of the diet, keeping the phenylalanine level below 15 mg/dl until the end of the adolescence and below 20 to 25 mg/dl in adulthood. All PKU patients must be followed up for life, in order to screen those who may not bear the diet relaxation and in order to strictly prevent maternal PKU deleterious consequences.

Early prognostic factors for intellectual outcome in CHARGE syndrome.

CHARGE syndrome (coloboma, heart disease, atresia of the choanae, retarded growth and mental development, genital anomalies, and ear malformations and hearing loss) is a heterogeneous condition for which early prediction of intellectual outcome is important but difficult. The psychomotor milestones and intellectual outcome of a consecutive series of children with CHARGE syndrome who were observed by the same team from the neonatal period to the time of study were analyzed retrospectively. Twenty-one children (11 males and 10 females, aged from 5 to 12 years, mean 8 years 7 months, SD 2 years 5 months) were included. The influence of 19 early identifiable parameters that could be considered as deleterious for intellectual outcome was recorded. Generally, the main psychomotor milestones (0 to 4 years) were severely delayed, although intellectual outcome (at primary-school age) was satisfactory for half the children in this series. We show that extensive bilateral coloboma resulting in low vision, microcephaly, and brain malformation were the only three parameters that were predictive of poor intellectual outcome. Conversely, severe neonatal medical conditions, such as tracheotomy, conditions requiring long stays in hospital, or cardiac surgery were not predictive of poor intellectual outcome. Severe hearing loss was not found to be negatively correlated with intellectual outcome once coloboma had been taken into account.

Adrenal insufficiency and abnormal genitalia in a 46XX female with Smith-Lemli-Opitz syndrome.

OBJECTIVE: To report the first case of a 46XX female infant with Smith-Lemli-Opitz syndrome (SLOS), adrenal insufficiency and abnormal genitalia. METHODS: The patient was assessed for hormonal status on day 4 and 6 months later and was followed-up from the study time (2.5 years of age). RESULTS: The patient had a persistent urogenital sinus, posterior labial fusion without clitoromegaly. She presented with a salt-wasting syndrome on day 4. Adrenal insufficiency was confirmed. Adrenal androgen levels, including 17-hydroxyprogesterone and 11-deoxycortisol were moderately elevated. CONCLUSION: Children with SLOS should be assessed for adrenal insufficiency. In female infants, abnormal external genitalia can be observed even if the precise mechanism behind these abnormalities is yet to be determined.