Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity.

Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation ("handshake"), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.

Garlic-induced face burn.

There is inadequate research and study into the use of garlic and other herbal medicine in clinical practice; accordingly, the general population should be cautious when using such complementary and herbal treatments. We report a case which highlights the potential complications following the application of garlic-related naturopathic remedies mostly on skin burns.

Downregulation of the GHRH/GH/IGF1 axis in a mouse model of Börjeson-Forssman-Lehman syndrome.

Börjeson-Forssman-Lehmann syndrome (BFLS) is an intellectual disability and endocrine disorder caused by plant homeodomain finger 6 (PHF6) mutations. Individuals with BFLS present with short stature. We report a mouse model of BFLS, in which deletion of Phf6 causes a proportional reduction in body size compared with control mice. Growth hormone (GH) levels were reduced in the absence of PHF6. Phf6-/Y animals displayed a reduction in the expression of the genes encoding GH-releasing hormone (GHRH) in the brain, GH in the pituitary gland and insulin-like growth factor 1 (IGF1) in the liver. Phf6 deletion specifically in the nervous system caused a proportional growth defect, indicating a neuroendocrine contribution to the phenotype. Loss of suppressor of cytokine signaling 2 (SOCS2), a negative regulator of growth hormone signaling partially rescued body size, supporting a reversible deficiency in GH signaling. These results demonstrate that PHF6 regulates the GHRH/GH/IGF1 axis.

Hyperbaric Oxygen Therapy for Large Composite Grafts: An Alternative in Pediatric Facial Reconstruction.

BACKGROUND: Management of pediatric facial defects can be challenging, as reattachment of large composite grafts is usually unsuccessful. Hyperbaric oxygen therapy (HBO) has been researched to augment composite graft survival, but clinical use for this application remains anecdotal. The authors present their successful experience managing select cases with large composite grafts and HBO as an adjunct. METHODS: A retrospective chart review identified children presenting with facial defects and managed operatively with large composite grafts (≥1.5 × 1.5 cm) and HBO therapy. Records were reviewed for defect characteristics, management details, and outcomes at last follow-up. RESULTS: Nine children (avg. 8.4 years, range 1.6-15.1) presented with ear or nose defects secondary to dog bites (n=7), falls (n=1), or congenital causes (n=1). Three experienced ear amputations, and six suffered nasal avulsions of varying degrees. All avulsed ears were reattached. Three cases of nose avulsions were reattached; the other three underwent secondary reconstruction with composite ear grafts. HBO was initiated immediately and continued for 8-10 days. All grafts survived at least 80% with no postoperative complications. At last follow-up (avg. 30.1 months; 0.8-63.9), all patients demonstrated good cosmetic results with minimal residual deformity. CONCLUSION: When reconstruction of pediatric facial defects warrants a large chondrocutaneous graft, immediate postoperative HBO therapy can increase survival. Particularly when reattaching amputated segments, if successful, this approach offers an anatomically ideal result without donor site morbidity. If unsuccessful, it does not "burn bridges" and decreases the extent of secondary reconstruction. The authors present their HBO protocol along with a review of available literature.

Latrodectus Facies After Latrodectus Hesperus Envenomation in a Pediatric Patient.

BACKGROUND: Black widow spider (Latrodectus spp) envenomation represents the most medically significant spider envenomation in the United States, prompting more than 2500 calls to poison centers annually. The female spider, which is responsible for symptomatic envenomations, is classically described as a shiny black spider with a red hourglass-shaped marking on the ventral abdomen. Clinical features of envenomation include painful muscle cramping, abdominal pain, and autonomic disturbances, such as tachycardia, hypertension, and diaphoresis. "Latrodectus facies" or "facies latrodectismica" is an additional distinctive but rarely described clinical finding characterized by periorbital edema, lacrimation, and blepharospasm. CASE REPORT: A 6-year-old female developed the typical clinical features of Latrodectus envenomation after being found in bed with a Western black widow spider (Latrodectus hesperus) with no ventral marking. She initially improved with opioid analgesia, but 6 h later her symptoms worsened again, and concurrent with this worsening she developed Latrodectus facies. She received additional opioid analgesia and all her symptoms resolved within 24 h. Her mother provided informed and written consent for the acquisition and publication of the facial photographs presented. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A high degree of clinical suspicion is necessary to correctly diagnose Latrodectus envenomation, especially when the spider escapes unnoticed or in young children in whom the bite is not witnessed. To our knowledge, Latrodectus facies has not been reported previously in a young child, and recognition of this finding will aid clinicians in limiting unnecessary interventions and administering appropriate therapy.

Rare association of cyclopia with craniospinal rachischisis.

Cyclopia is a severe form of holoprosencephaly which results in children being born with just one eye, absence of nose and presence of a proboscis above the median eye. Incidence of cyclopia is around 1.05 in 1, 00,000 births, including stillbirths. The association of anencephaly with spinal rachichisis varies from 17-50%. However, the existence of cyclopia with anencephaly and spinal rachischisis has been reported only in 9 cases till date. We report one more case of cyclopia with anencephaly and spinal rachischisis. Awareness of this spectrum of association with cyclopia, albeit rare, will help in early antenatal diagnosis by fetal ultrasonography. Public education and strict adherence to folic acid supplementation can prevent this unfortunate anomaly.

Prenatal features of Pena-Shokeir sequence with atypical response to acoustic stimulation.

A fetal sonographic screening examination performed at 23 weeks showed polyhydramnios, micrognathia, fixed postures of all long bones, but no movement and no breathing. The fetus showed fetal heart rate acceleration but no movement when acoustic stimulation was applied with artificial larynx. All these findings persisted on serial examinations. The neonate was stillborn at 37 weeks and a final diagnosis of Pena-Shokeir sequence was made. In addition to typical sonographic features of Pena-Shokeir sequence, fetal heart rate accelerations with no movement in response to acoustic stimulation suggests that peripheral myopathy may possibly play an important role in the pathogenesis of the disease. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:459-462, 2016.

[Clinico-biological and immunohaematological profile of patients with ß-thalassemia in Tunisia: about 26 cases]. / Profil clinico-biologique et immunohématologique des patients atteints de ß-thalassémie en Tunisie : à propos de 26 cas.

AIM OF THE STUDY: To study the clinical and biological profile of ß-thalassemic patients in our region, reflecting the quality of their care. PATIENTS AND METHODS: A retrospective study (2010-2011) on 26 ß-thalassemic patients followed in the pediatrics service at CHU Farhat Hached Sousse, Tunisia. Epidemiological, clinical and biological data were collected from medical records and transfusion files of patients. The transfusion protocol adopted was to maintain a hemoglobin level>10g/dL by regular transfusions every 3-4 weeks. Iron chelation therapy, in order to maintain serum ferritin<1500ng/mL, was introduced when serum ferritin exceeded 800-1000ng/mL. RESULTS: The mean age of patients at diagnosis was 15 months. The clinical impact of anemia had resulted in failure to thrive in 54% of patients and facial dysmorphism in 23%. The average transfusion requirement was estimated at 311.02mL/kg/year with 6 cases of hyperconsumption. The immunohaematological monitoring showed the appearance of anti-RBC alloimmunization in one patient and 4 cases of autoimmunization. Poor adherence of chelation therapy was 62% and causing 5 cases of cardiac complications, 4 cases of liver injury and 14 cases of endocrine complications. CONCLUSION: Improving the therapeutic care of ß-thalassemic children requires better monitoring of transfusion recovery and improved adherence to chelation therapy.

Rare ocular features in a case of Kabuki syndrome (Niikawa-Kuroki syndrome).

BACKGROUND: Kabuki syndrome is a multi-system disorder with peculiar facial features, and ophthalmic abnormalities are frequently involved. This case report of a child with Kabuki syndrome describes two new previously unreported ophthalmic conditions. CASE PRESENTATION: A 3-year-old Taiwanese boy with Kabuki syndrome had a short stature, spinal dysraphism, intellectual disability and typical facial features. Ophthalmic findings which have been previously reported in the literature and in this patient, included ptosis, esotropia, coloboma of the iris, retina, choroid and optic disc, and microcornea. The newly identified ophthalmic features in this patient included colobomatous microphthalmos and a dysplastic and elevated disc without central cupping. The genetic analysis identified an MLL2 gene mutation. CONCLUSION: The presentations of a dysplastic disc and colobomatous microphthalmia are rarely reported in patients with Kabuki syndrome, but these ophthalmic abnormalities may affect vision. Detailed ophthalmic evaluations in children with Kabuki syndrome are advised.

Investigation on maternal physiological and psychological factors of cheilopalatognathus.

OBJECTIVE: Case-control study on mothers of cheilopalatognathus children was conducted, to investigate the maternal physiological and psychological factors for occurrence of cheilopalatognathus. MATERIALS AND METHODS: One hundred ten mothers of cheilopalatognathus children who were scheduled for one-stage surgery were selected as a research group, and 110 mothers of normal children served as a normal control group at the same time. Trait Anxiety Inventory (T-AI), Life Events Scale (LES), Trait Coping Style Questionnaire (TCSQ), Type C Behavior Scale (CBS), adult Eysenck Personality Questionnaire (EPQ), and homemade general questionnaire survey were employed for the investigation. RESULTS: Compared with the control group, the scores for negative event tension value, anxiety, and depressive factors were higher in the study group (p < 0.05); while the scores for positive event tension value, intellect, optimism, and social support factors were lower (p < 0.05). Regression analysis found that physiological factors included were five: education, changes in body weight during pregnancy, the intake amount of milk and beans, and intake of healthcare products, and supplementary folic acid taken or not, while the psychological factors included were four: positive event stimulation, negative event stimulation, the amount of social support, as well as introvert and extrovert personalities. CONCLUSION: The study results suggest that pregnant women's physiological and psychological factors can cause changes in cheilopalatognathus incidence, which is expected to be guidance for healthcare during pregnancy, to prevent the occurrence of cheilopalatognathus.

Maternal diet supplementation with methyl donors and increased parity affect the incidence of craniofacial defects in the offspring of twisted gastrulation mutant mice.

Diets rich in methyl-donating compounds, including folate, can provide protection against neural tube defects, but their role in preventing craniofacial defects is less clear. Mice deficient in Twisted gastrulation (TWSG1), an extracellular modulator of bone morphogenetic protein signaling, manifest both midline facial defects and jaw defects, allowing study of the effects of methyl donors on various craniofacial defects in an experimentally tractable animal model. The goal of this study was to examine the effects of maternal dietary supplementation with methyl donors on the incidence and type of craniofacial defects among Twsg1(-/-) offspring. Nulliparous and primiparous female mice were fed an NIH31 standard diet (control) or a methyl donor supplemented (MDS) diet (folate, vitamin B-12, betaine, and choline). Observed defects in the pups were divided into those derived mostly from the first branchial arch (BA1) (micrognathia, agnathia, cleft palate) and midline facial defects in the holoprosencephaly spectrum (cyclopia, proboscis, and anterior truncation). In the first pregnancy, offspring of mice fed the MDS diet had lower incidence of BA1-derived defects (12.8% in MDS vs. 32.5% in control; P = 0.02) but similar incidence of midline facial defects (6.4% in MDS vs. 5.2% in control; P = 1.0). Increased maternal parity was independently associated with increased incidence of craniofacial defects after adjusting for diet (from 37.7 to 59.5% in control, P = 0.04 and from 19.1 to 45.3% in MDS, P = 0.045). In conclusion, methyl donor supplementation shows protective effects against jaw defects, but not midline facial defects, and increased parity can be a risk factor for some craniofacial defects.

The hypothetical role of congenital hypotonia in the development of early coronoid hyperplasia.

BACKGROUND: Coronoid hyperplasia (CH) is an abnormal bony elongation of a histologically normal coronoid process. Its definitive cause remains unknown. OBJECTIVES: To analyze the possible implication of congenital hypotonia in the pathogenesis of early coronoid overgrowth. PATIENTS AND METHODS: Two infants with congenital hypotonia were evaluated for limited mouth aperture. Bilateral CH was diagnosed. Transoral coronoidectomy was followed by an early dynamic physiotherapy program. RESULTS: Significant improvement of maximum interincisal opening was achieved. The review of the scientific literature proved the diagnosis of CH in the infant age group is extremely unusual and the etiology of the condition is still uncertain. CONCLUSIONS: Besides mouth opening restriction, clinical features of coronoid hyperplasia in infants can include suction or deglutition anomalies, failure to thrive and recurrent episodes of choking or aspiration pneumonia. The authors hypothesize reduced fetal mandibular movements and deglutition as a result of congenital hypotonia may lead to relative hyperactivity of the temporalis muscle that is not counterbalanced by the infra and suprahyoid muscles, thereby facilitating coronoid overgrowth.

Frontonasal dysplasia: clinical evaluation on audiological and brainstem electrophysiological profiles.

UNLABELLED: Frontonasal dysplasia (FND) is a rare malformative complex affecting the frontal portion of the face, the eyes and the nose; it may occur singly or associated with other clinical signs. No systematic studies describing hearing in this condition were found. AIM: To evaluate hearing sensitivity and sound stimulus conduction from cochlea to brainstem in patients with clinical signs of FND. METHODS: 21 patients with isolated or syndromic FND were submitted to a clinical (otological/vestibular antecedents and otoscopy) and instrumental (pure tone and speech audiometry, tympanometry and brainstem auditory evoked response) hearing evaluation. DESIGN: A clinical, cross-sectional observational prospective study. RESULTS: Hearing thresholds were normal in 15 (70%) patients, abnormal in 5 (25%), mostly with conductive hearing loss; one patient did not cooperate with testing. The tympanometric curve was type A in 30 (72%) ears, type C in 5 (12%), type As in 4 (9%) and type B in 3 (7%). The auditory brainstem response (ABR) showed no abnormalities. CONCLUSION: Patients with FND showed no abnormalities in the auditory system from cochlea to brainstem in this study. Mild conductive hearing loss found in some is probably related to cleft palate. Further evaluation of hearing pathways at higher levels is recommended.

Frontonasal dysplasia: clinical evaluation on audiological and brainstem electrophysiological profiles / Displasia frontonasal: avaliação clínica e eletrofisiológica da audição

Frontonasal dysplasia (FND) is a rare malformative complex affecting the frontal portion of the face, the eyes and the nose; it may occur singly or associated with other clinical signs. No systematic studies describing hearing in this condition were found. AIM: To evaluate hearing sensitivity and sound stimulus conduction from cochlea to brainstem in patients with clinical signs of FND. METHODS: 21 patients with isolated or syndromic FND were submitted to a clinical (otological/vestibular antecedents and otoscopy) and instrumental (pure tone and speech audiometry, tympanometry and brainstem auditory evoked response) hearing evaluation. DESIGN: A clinical, cross-sectional observational prospective study. RESULTS: Hearing thresholds were normal in 15 (70 percent) patients, abnormal in 5 (25 percent), mostly with conductive hearing loss; one patient did not cooperate with testing. The tympanometric curve was type A in 30 (72 percent) ears, type C in 5 (12 percent), type As in 4 (9 percent) and type B in 3 (7 percent). The auditory brainstem response (ABR) showed no abnormalities. CONCLUSION: Patients with FND showed no abnormalities in the auditory system from cochlea to brainstem in this study. Mild conductive hearing loss found in some is probably related to cleft palate. Further evaluation of hearing pathways at higher levels is recommended.

A displasia frontonasal (DFN) representa um complexo malformativo que afeta os olhos, o nariz e a região frontal da face. Estudos específicos com o objetivo de estudar a audição na DFN não foram encontrados na literatura. OBJETIVO: Avaliar o sistema auditivo em indivíduos com DFN quanto à acuidade e condução do estímulo sonoro até o tronco encefálico. MATERIAL E MÉTODO: 21 pacientes na faixa etária de 7 a 42 anos, sendo 14 do sexo feminino e 7 do sexo masculino, com DFN isolada ou sindrômica, foram submetidos à anamnese, meatoscopia, imitanciometria, audiometria tonal liminar e potenciais evocados auditivos de tronco encefálico (PEATE). FORMA DE ESTUDO: Estudo de série clínico prospectivo. RESULTADOS: Limiares audiométricos normais em 15 (70 por cento) indivíduos e alterados em 5 (25 por cento), sendo perda auditiva condutiva na maior parte. Na timpanometria, 30 orelhas (72 por cento) apresentaram curva tipo A, 5 (12 por cento) tipo C, 4 (9 por cento) tipo Ar e 3 (7 por cento) tipo B. Os valores das latências absolutas e interpicos do PEATE foram normais. CONCLUSÕES: Não foram encontradas alterações na via auditiva até o tronco encefálico. As alterações condutivas são provavelmente relacionadas às patologias de orelha média decorrentes da fissura de palato. Sugerimos a avaliação de níveis mais altos dentro do sistema auditivo.

Dysmorphological and pharmacological studies in 4q- syndrome.

The 4q- syndrome includes interstitial and terminal deletions of the long arm of chromosome 4. In this study 22 children with 4q- were evaluated through face-to-face assessments and/or two-dimensional digital photographs. In addition, 15 parents participated in a questionnaire survey regarding pharmacological and other treatments which their affected child received. A high forehead was seen in 73% of index cases and was the only facial feature consistently present in this group. There may be a link between this phenotypic characteristic and the increased incidence of autistic spectrum disorder in 4q deletion syndrome (33%). Two thirds of the subjects were taking long term prescription drugs and/or food supplements. Commonly used nutritional supplements were multivitamins, carnitine, coenzyme Q10 and omega-3 fatty acids. They were well tolerated by the probands but the literature evidence for their specific effectiveness was weak. Twelve out of 15 children had speech and language therapy, occupational therapy or physiotherapy, and 6/15 regularly saw a psychologist. Future 4q- research should focus on gene-phenotype correlations, 3D face analysis and drug treatment to improve global and medical functioning.

Malformaciones y parálisis faciales en la cerámica de las culturas precolombinas Moche y Lambayeque / Evidence of facial palsy and facial malformations in pottery from Peruvian Moche and Lambayeque pre-Columbian cultures

Introducción. Las culturas Moche (100-700 d.C.) y Lambayeque o Sicán (750-1100 d.C.) son culturas precolombinas pertenecientes al período de los estados regionales que se desarrollaron en el norte de Perú. Se ha obtenido abundante información sobre la vida cotidiana, la religión y la medicina mediante el estudio de las cerámicas encontradas en los entierros de los señores y sacerdotes Moche en las huacas, pirámides y templos sagrados. Objetivo. Describir las evidencias arqueológicas de la medicina Moche y las enfermedades neurológicas mostradas en sus restos cerámicos. Material y métodos. Estudiamos las representaciones de las enfermedades en la iconografía y cerámicas Moche y Lambayeque expuestas en el Museo Arqueológico Casinelli de Trujillo y el Museo Arqueológico Nacional Brüning de Lambayeque, Perú. Se documentaron fotográficamente los casos más llamativos previa autorización de las autoridades de los museos. Resultados. Observamos cerámicas que representan sujetos afectos de parálisis facial periférica, malformaciones faciales (labio leporino), un posible espasmo hemifacial, pacientes con amputaciones de brazos y pies, sujetos siameses y sujetos con cifoescoliosis. También observamos vasos ceremoniales de los médicos Moche, hombre y mujer, tratando a los enfermos. Conclusiones. Las principales entidades representadas en la cerámica Moche y Lambayeque son la parálisis facial periférica y las malformaciones faciales de tipo labio leporino. Estas representaciones constituyen uno de los primeros registros de estas patologías en las culturas precolombinas de Sudamérica (AU)

INTRODUCTION: Moche (100-700 AD) and Lambayeque-Sicán (750-1100 AD) are pre-Columbian cultures from Regional States Period, developed in Northern Peru. Information about daily life, religion and medicine has been obtained through the study of Moche ceramics found in lords and priests tombs, pyramids and temples. OBJECTIVE: To analyze archeological evidences of Moche Medicine and neurological diseases through ceramics. MATERIAL AND METHODS: Representations of diseases in Moche and Lambayeque iconography and Moche pottery collections exposed in Casinelli museum from Trujillo, and Brüning National Archeological museum from Lambayeque, Peru, were studied. The most representative cases were analyzed and photographed, previous authorization from authorities and curators of the museums. RESULTS: The following pathologies were observed in ceramic collections: peripheral facial palsy, facial malformations such as cleft lip, hemifacial spasm, legs and arm amputations, scoliosis and Siamese patients. Male and females Moche doctors were also observed in the ceramics in ritual ceremonies treating patients. CONCLUSIONS: The main pathologies observed in Moche and Lambayeque pottery are facial palsy and cleft lip. These are one of the earliest registries of these pathologies in pre-Columbian cultures in South-America (AU)

[Evidence of facial palsy and facial malformations in pottery from Peruvian Moche and Lambayeque pre-Columbian cultures]. / Malformaciones y parálisis faciales en la cerámica de las culturas precolombinas Moche y Lambayeque.

INTRODUCTION: Moche (100-700 AD) and Lambayeque-Sicán (750-1100 AD) are pre-Columbian cultures from Regional States Period, developed in Northern Peru. Information about daily life, religion and medicine has been obtained through the study of Moche ceramics found in lords and priests tombs, pyramids and temples. OBJECTIVE: To analyze archeological evidences of Moche Medicine and neurological diseases through ceramics. MATERIAL AND METHODS: Representations of diseases in Moche and Lambayeque iconography and Moche pottery collections exposed in Casinelli museum from Trujillo, and Brüning National Archeological museum from Lambayeque, Peru, were studied. The most representative cases were analyzed and photographed, previous authorization from authorities and curators of the museums. RESULTS: The following pathologies were observed in ceramic collections: peripheral facial palsy, facial malformations such as cleft lip, hemifacial spasm, legs and arm amputations, scoliosis and Siamese patients. Male and females Moche doctors were also observed in the ceramics in ritual ceremonies treating patients. CONCLUSIONS: The main pathologies observed in Moche and Lambayeque pottery are facial palsy and cleft lip. These are one of the earliest registries of these pathologies in pre-Columbian cultures in South-America.

Coumarin embryopathy in an extremely low birth weight infant associated with neonatal hepatitis and ocular malformations.

Coumarin embryopathy (CE) is a well-documented sequelae of prenatal exposure to vitamin K antagonists. We report on a female premature infant (25 weeks' gestation) born to a mother who had received phenprocoumon during pregnancy following mechanical heart valve replacement. The infant presented with impaired coagulation, intraventricular and minor parenchymal cerebral haemorrhages and midface hypoplasia typical of CE. In addition, there was hepatopathy with conjugated hyperbilirubinemia, elevated liver enzymes and repeated episodes of hypoglycemia upon attempts to discontinue glucose supplementation, all lasting for 4 months. There was corneal opacity with anterior segment dygenesis in the left eye, and persistent pupillary membrane, cataract and persistent hyperplastic primary vitreous in the right eye. While liver disease is an uncommon but serious side effect of vitamin K antagonists, this is the first report describing neonatal hepatopathy as part of CE. In anticoagulation of pregnant women with mechanical heart valves, vitamin K antagonists should be used with utmost restraint.

Striking facial dysmorphisms and restricted thymic development in a fetus with a 6-megabase deletion of chromosome 14q.

During routine ultrasound screening at 12 weeks 5 days of gestation, a nuchal translucency of 7 mm, an omphalocele, and fetal hydrops were found and prompted chorionic villus sampling at 13 weeks 2 days. Chromosome analysis showed an unbalanced karyotype with an abnormal chromosome 14. The mother was a carrier of a translocation karyotype 46,XX,t(13;14) (q34;q32.2). In the fetus this gave rise to a partial trisomy 13q and partial monosomy 14q (fetal karyotype: 46,XX,der[14]t[13;14][q34;q32.2]). By Array-CGH on DNA extracted from a postmortem skin culture, a duplication of approximately 1.7 Mbp of the distal part of chromosome 13q34 and a deletion of approximately 6.0 Mbp of the distal part of chromosome 14q32.2 was demonstrated. Postmortem findings after termination of pregnancy at 14 weeks 6 days included, among others, a severe hypoplasia of the median part of the maxilla, no recognizable nose, a broad median palatoschisis, nonlobulated lungs, a horseshoe kidney with multicystic dysplasia, and decreased development of cortical cellularity in the thymus. These clinical manifestations and autopsy findings of the fetus are compared with those of previously published cases and the possible involvement in this pathology of the YY1 and JAG2 transcription factors and the BCL11b and SIVA-1 regulators of thymic development is discussed.

Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome in triplets.

We report female triplets with the clinical and biochemical manifestations of hypoparatyroidism-retardation-dysmorphism (HRD) syndrome also known as Sanjad-Sakati syndrome. They were born at 35 weeks gestation after assisted pregnancy (in vitro fertilization). The parents are first degree cousins from Saudi Arabia.