Early mother-child interaction and later quality of attachment in infants with an orofacial cleft compared to infants without cleft.

Objective : The main objective of this study was to assess mother-child patterns of interaction in relation to later quality of attachment in a group of children with an orofacial cleft compared with children without cleft. Design : Families were contacted when the child was 2 months old for a direct assessment of mother-child interaction and then at 12 months for a direct assessment of the child's attachment. Data concerning socioeconomical information and posttraumatic stress symptoms in mothers were collected at the first appointment. Participants : Forty families of children with a cleft and 45 families of children without cleft were included in the study. Families were recruited at birth in the University Hospital of Lausanne. Results : Results showed that children with a cleft were more difficult and less cooperative during interaction at 2 months of age with their mother compared with children without a cleft. No significant differences were found in mothers or in dyadic interactive styles. Concerning the child's attachment at 12 months old, no differences were found in attachment security. However, secure children with a cleft were significantly more avoidant with their mother during the reunion episodes than secure children without cleft. Conclusion : Despite the facial disfigurement and the stress engendered by treatment during the first months of the infant's life, children with cleft and their mothers are doing as well as families without cleft with regard to the mothers' mental health, mother-child relationships, and later quality of attachment. A potential contribution for this absence of difference may be the pluridisciplinary support that families of children with cleft benefit from in Lausanne.

Factors influencing maternal mental health after the birth of a child with a cleft in benin and in Switzerland.

Objective: The main objective of the study is to identify practical and cultural factors influencing the mental health of mothers of children with an orofacial cleft in Benin and to compare it with a sample of Swiss mothers in the same conditions. Method: Thirty-six mothers of children with an orofacial cleft in Benin and 40 mothers of children with an orofacial cleft in Switzerland were interviewed about practical and emotional aspects concerning their child and their own lives. Then, they completed the Perinatal Postraumatic Stress Questionnaire and the Beck Depression Inventory. Results: Mothers in Benin had significantly higher posttraumatic stress and depression symptoms compared with mothers in Switzerland. Depression symptoms were higher in Beninese mothers coming from urban areas, in Beninese mothers with few or no other children, and in Beninese mothers whose child was operated on at a more advanced age. Discussion: This study stressed the importance of cultural differences in perceptions of orofacial clefts in order to provide appropriate care to patients and their families. In particular, wide campaigns of information should help parents to understand the cleft origin and the medical staff in small dispensaries to provide adequate support and care. This may diminish anxiety concerning the child's short- and long-term prognosis. Creation of a Beninese parental support group for children with clefts and their families could be another way to provide information and support where multidisciplinary care is not available.

Epidémiologie des fentes labio-maxillo-palatines dans le canton de Vaud [Epidemiology of lip-maxilla-palate clefts in the canton of Vaud]

Epidemiological variables in oral clefts were examined in a cohort of patients with congenital malformations from the canton of Vaud in Switzerland during the years 1990-1999. Among 77'259 newborns or foetuses, 144 cases of oral clefts were identified in the Registre Vaudois des Anomalies Congénitales (RVAC), yielding a total prevalence of 18.6 per 10'000. These clefts consisted of 84 (58%) cases of cleft lip with or without cleft palate (CL/P) and 60 (42%) cases of cleft palate only (CP). Associated anomalies were found in 45% of cases. Our results are compared with previous reports in other parts of Europe.

Complete bilateral facial cleft (Tessier 4) with corneal staphyloma: a rare association.

The oro-ocular cleft no. 4 according to the Tessier classification is one of the rarest facial cleft, and to this day, few cases have been reported in the literature. We describe the case of a 9-month-old girl with a complete bilateral facial cleft. On the right cornea protruded a hard lesion, a corneal staphyloma. We describe the 3 primary surgical steps used to restore the possibility of satisfactory feeding, to promote language acquisition, and to protect vision in the nonaffected eye. The psychological and social aspects of severe facial deformities in developing countries are also tackled.

Chondrodysplasia and Abnormal Joint Development Associated with Mutations in IMPAD1, Encoding the Golgi-Resident Nucleotide Phosphatase, gPAPP.

We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, a Golgi-resident nucleotide phosphatase that hydrolyzes phosphoadenosine phosphate (PAP), the byproduct of sulfotransferase reactions, to AMP. The mutations affected residues in or adjacent to the phosphatase active site and are predicted to impair enzyme activity. A fourth unrelated patient was subsequently found to be homozygous for a premature termination codon in IMPAD1. Impad1 inactivation in mice has previously been shown to produce chondrodysplasia with abnormal joint formation and impaired proteoglycan sulfation. The human chondrodysplasia associated with gPAPP deficiency joins a growing number of skeletoarticular conditions associated with defective synthesis of sulfated proteoglycans, highlighting the importance of proteoglycans in the development of skeletal elements and joints.

Success and Failure for Children Born with Facial Clefts in Africa: A 15-Year Follow-up.

BACKGROUND: This study reviews the 15 year program of our Department of Pediatric Surgery for the treatment and follow-up of children born with a cleft in Benin and Togo. METHODS: We analyzed files of children born in Africa with a cleft. They were referred to us through a nongovernmental organization (NGO) between 1993 and 2008 and assessed in Africa by local pediatricians before and after surgery. Operations were performed by our team. RESULTS: Two hundred files were reviewed: 60 cases of unilateral cleft lip, seven of bilateral cleft lip, 44 of unilateral cleft lip palate (UCLP), 29 of bilateral cleft lip palate (BCLP), 53 of cleft palate (CP), three of bilateral oro-ocular cleft, one of unilateral and two of median clefts (Binder), and one of commissural cleft. Sixty-nine (35 %) of these cases were not operated in Africa: 25 (12.5 %) had not shown up, 28 (15 %) were considered unfit for surgery (Down's syndrome, HIV-positive, malnutrition, cardiac malformation), and 16 (7.5 %) were transferred to Switzerland. Palatal fistula occurred in 20 % of UCLP, 30 % of BCLP, and 16 % of CP. Evaluation of speech after palate surgery gave less than 50 % of socially acceptable speech. CONCLUSIONS: Our partnership with a NGO and a local team makes it possible to treat and subsequently follow children born with a cleft in West Africa. Surgery is performed under good conditions. If aesthetic results are a success, functional results after palate surgery need further improvement to promote integration in school and social life.

Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, which is characterized by cleft palate and severe defects of the skin, is an autosomal dominant disorder caused by mutations in the gene encoding transcription factor p63. Here, we report the generation of a knock-in mouse model for AEC syndrome (p63(+/L514F) ) that recapitulates the human disorder. The AEC mutation exerts a selective dominant-negative function on wild-type p63 by affecting progenitor cell expansion during ectodermal development leading to a defective epidermal stem cell compartment. These phenotypes are associated with impairment of fibroblast growth factor (FGF) signalling resulting from reduced expression of Fgfr2 and Fgfr3, direct p63 target genes. In parallel, a defective stem cell compartment is observed in humans affected by AEC syndrome and in Fgfr2b(-/-) mice. Restoring Fgfr2b expression in p63(+/L514F) epithelial cells by treatment with FGF7 reactivates downstream mitogen-activated protein kinase signalling and cell proliferation. These findings establish a functional link between FGF signalling and p63 in the expansion of epithelial progenitor cells and provide mechanistic insights into the pathogenesis of AEC syndrome.

Prenatal diagnosis of dysmorphic syndromes by routine fetal ultrasound examination across Europe.

OBJECTIVES: Ultrasound scan in the mid-trimester of pregnancy is now a routine part of prenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of dysmorphic syndromes by fetal ultrasound examination. METHODS: Data from 20 registries of congenital malformations in 12 European countries were included in the study. RESULTS: There were 2454 cases with congenital heart diseases, 479 of which were recognized syndromes, including 375 chromosomal anomalies and 104 syndromes without chromosomal anomalies. Fifty-one of the 104 were detected prenatally (49.0%). One hundred and ninety-two of 1130 cases with renal anomalies were recognized syndromes, including 128 chromosomal anomalies and 64 syndromes without chromosomal anomalies; 162 of them (84.4%) were diagnosed prenatally, including 109 chromosomal anomalies and 53 non-chromosomal syndromes. Fifty-four of the 250 cases with limb defects were recognized syndromes, including 16 chromosomal syndromes and 38 syndromes without chromosomal anomalies; 21 of these 54 syndromes were diagnosed prenatally (38.9%), including 9 chromosomal syndromes. There were 243 cases of abdominal wall defects including 57 recognizable syndromes, 48 with omphalocele and 9 with gastroschisis; 48 were diagnosed prenatally (84.2%). Twenty-six of the 187 cases with diaphragmatic hernia had recognized syndromes, including 20 chromosomal aberrations and 6 syndromes without chromosomal anomalies. Twenty-two of them (84.6%) were detected prenatally. Sixty-four of 349 cases with intestinal anomalies were recognized syndromes; 24 were diagnosed prenatally (37.5%). There were 553 cases of cleft lip and palate (CL(P)) and 198 of cleft palate (CP) including 74 chromosomal anomalies and 73 recognized non-chromosomal syndromes. Prenatal diagnosis was made in 51 cases of CL(P) (53.7%) and 7 of CP (13.7%). Twenty-two of 188 anencephalic cases were syndromic and all were diagnosed prenatally. Of 290 cases with spina bifida, 18 were recognized syndromes, and of them 17 were diagnosed prenatally. All 11 syndromic encephaloceles were diagnosed prenatally. CONCLUSIONS: Around 50% of the recognized syndromes which are associated with major congenital anomalies (cardiac, renal, intestinal, limb defects, abdominal wall defects and oral clefts) can be detected prenatally by the anomaly scan. However the detection rate varies with the type of syndrome and with the different countries' policies of prenatal screening.

Complete Maxillo-Mandibular Syngnathia in a Newborn with Multiple Congenital Malformations.

Syngnathia is an extremely rare condition involving congenital fusion of the maxilla with the mandible. Clinical presentations vary from simple mucosal bands (synechiae) to complete bony fusion (synostosis). Most cases are unilateral incomplete fusions. We report the case of a severely growth-retarded newborn infant with complete synostosis of the mandible with the maxilla and the zygoma associated with cleft palate, choanal atresia, deafness, delayed cerebral white matter development, and genital and limb malformations. Extensive genetic analysis did not reveal any mutations. This association of multiple congenital malformations may represent an entity distinct from previously described syndromes associated with syngnathia.

Speech prognosis and need of pharyngeal flap for non syndromic vs syndromic Pierre Robin Sequence

BACKGROUND: The aim of this retrospective study was to evaluate speech outcome and need of a pharyngeal flap in children born with nonsyndromic Pierre Robin Sequence (nsPRS) vs syndromic Pierre Robin Sequence (sPRS). METHODS: Pierre Robin Sequence was diagnosed when the triad microretrognathia, glossoptosis, and cleft palate were present. Children were classified at birth in 3 categories depending on respiratory and feeding problems. The Borel-Maisonny classification was used to score the velopharyngeal insufficiency. RESULTS: The study was based on 38 children followed from 1985 to 2006. For the 25 nsPRS, 9 (36%) pharyngeal flaps were performed with improvements of the phonatory score in the 3 categories. For the 13 sPRS, 3 (23%) pharyngeal flaps were performed with an improvement of the phonatory scores in the 3 children. There was no statistical difference between the nsPRS and sPRS groups (P = .3) even if we compared the children in the 3 categories (P = .2). CONCLUSIONS: Children born with nsPRS did not have a better prognosis of speech outcome than children born with sPRS. Respiratory and feeding problems at birth did not seem to be correlated with speech outcome. This is important when informing parents on the prognosis of long-term therapy

Atelosteogenesis Type 2

Disease characteristics. Clinical features of atelosteogenesis type 2 (AO2) include rhizomelic limb shortening with normal-sized skull, hitchhiker thumbs, small chest, protuberant abdomen, cleft palate, and distinctive facial features (midface hypoplasia, depressed nasal bridge, epicanthus, micrognathia). Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. AO2 is lethal at birth or shortly thereafter because of pulmonary hypoplasia and tracheobronchomalacia. Diagnosis/testing. The diagnosis of AO2 rests on a combination of clinical, radiologic, and histopathologic features. SLC26A2 (DTDST) is the only gene currently known to be associated with AO2. The diagnosis can be confirmed by molecular genetic testing of SLC26A2, which is clinically available. Management. Treatment of manifestations: palliative care for liveborns. Genetic counseling. AO2 is inherited in an autosomal recessive manner. At conception, each sib of a proband with AO2 has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Prenatal diagnosis for pregnancies at 25% risk is possible. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both disease-causing alleles in the family are known and the carrier status of the parents has been confirmed. Ultrasound examination early in pregnancy is a reasonable complement or alternative to molecular genetic prenatal diagnosis.

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice.

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1(tm1a)) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.

Descriptive epidemiology of Cornelia de Lange syndrome in Europe.

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed <or=2,500 g. Low birth weight correlated with a more severe phenotype. Severe limb anomalies were significantly more often present in males.