Branchio‐oto‐renal syndrome: Comprehensive review based on nationwide surveillance in Japan

Branchio‐oto‐renal (BOR) syndrome is an autosomal dominant disorder characterized by branchiogenic malformation, hearing loss and renal anomalies. The prevalence of BOR syndrome is 1/40 000 in Western countries, and nationwide surveillance in 2009–2010 identified approximately 250 BOR patients in Japan. Three causative genes for BOR syndrome have been reported thus far: EYA1, SIX1, and SIX5, but the causative genes for approximately half of all BOR patients remain unknown. This review article discusses the epidemiology, clinical symptoms, genetic background and management of BOR syndrome.     

Congenital unilateral facial nerve palsy as an unusual presentation of BOR syndrome

Congenital facial nerve palsy (CFNP) is a rare condition that can be generally categorized as developmental or traumatic. Though trauma during birth is the most common cause, sometimes CFNP is observed in association with genetic syndromes and congenital hearing loss and structural anomalies of the middle and inner ear. CFNP is infrequently reported in association with branchio–oto–renal (BOR) syndrome. We present a case of a 4-day-old infant girl with a familial history of renal disease, who was hospitalized because of congenital unilateral facial palsy, which subsequently appeared to be a part of BOR syndrome and led to the diagnosis of congenital bilateral renal hypoplasia, renal failure, and secondary arterial hypertension. This case proves that sometimes rare manifestations of BOR syndrome may be one of the first signs of an underlying syndrome. Issues regarding patterns of BOR syndrome inheritability and expressivity that we encountered are also discussed. Patients with a familial history of BOR syndrome should be carefully inspected after birth, especially in suspected cases such as newborns with preauricular pits and/or facial nerve palsy.     

Second branchial cleft anomalies in children: a literature review

Branchial cleft anomalies are the second most common head and neck congenital lesions in children. It may sometimes be a part of branchio-oto-renal (BOR) syndrome, so in patients with branchial cleft anomalies associated with a complaint of auricular deformity or a similar history and findings in other family members, we should take an additional examination to find the possibility of BOR syndrome. Complete excision is essential for good prognosis. For the management of branchial cleft anomalies, various methods have been reported. Endoscopically assisted dissection technique and transoral robot-assisted surgery were used in the management of fistula and allowed excellent visualization of the pharyngeal component of the lesion and a minimally invasive approach. It is essential for the surgeon to fully comprehend the congenital lesions to attain the correct preoperative diagnosis and plan for an appropriate surgical approach to prevent the most common complication and recurrence in these lesions. The following sections discuss the anatomy, common presentation, auxiliary examination, differential diagnosis, the current principles of surgical treatment and prognosis for second branchial cleft anomalies in children, and discussed the branchio-oto-renal syndrome.     

Familial interruption of the aortic arch

Summary Interruption of the aortic arch (IAA) is an important congenital cardiac malformation occurring in 1.4% of cases with a congenital cardiac malformation. Only two reports have described IAA in siblings, each with type B and an anomalous right subclavian artery. We report the occurrence of IAA type B with an anomalous right subclavian artery in two siblings and their half-sibling, each of whom had additional conotruncal cardiac malformations. Recent evidence suggests that conotruncal cardiac malformations, including IAA type B, are related to abnormalities of neural crest cell migration. Thus, the family reported herein may manifest a syndrome related to alterations in mesenchymal tissue/neural crest cell migration.     

Townes-Brocks syndrome

A 2-week-old male is presented with the clinical findings of the autosomal dominant Townes-Brocks syndrome in an otherwise unaffected family. The patient showed the full spectrum of anomalies including imperforate anus, perineal fistula, triphalangeal thumb, preaxial polydactyly, pre-auricular tags, and microtia. As there is considerable overlap with the VACTERL association, careful examination of the parents is necessary with regard to the genetic counselling risk.     

Multiple Pterygium Syndrome type Escobar in two brothers Follow-up data from childhood to adulthood

We present two brothers with Multiple Pterygium Syndrome type Escobar. Characteristic findings in this autosomal recessively inherited pterygium syndrome are, in addition to multiple pterygia, short stature, cleft palate, vertebral fusion defects and minor facial anomalies. The adult height in the two male siblings was below the third centile. Secondary sexual development and testicular size were normal, in contrast with the cryptorchidism and pubertal delay documented in most young patients.     

Postmortem angiocardiography in newborn infants with congenital malformation of the heart and great vessels

In congenital malformations of the heart and great vessels with a fatal outcome a postmortem angiocardiography may contribute to diagnosis. In this technique the heart is not dissected and the topographical relationships remain unchanged. A postmortem angiocardiography is of particular interest if no autopsy is to be performed. Some patho-anatomical details are demonstrated in three selected cases: newborn infants with 1. hypoplastic left heart syndrome, 2. truncus arteriosus communis with interruption of the aortic arch, and 3. aottic-left ventricular tunnel.     

Bevacizumab treatment in multifocal lymphangioendotheliomatosis with thrombocytopenia

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disorder characterized by a proliferation of cutaneous and gastrointestinal (GI) lesions that have characteristics of both lymphatic and vascular lesions. Thrombocytopenia is associated with this syndrome and is thought to represent platelet destruction within the lesions. The natural history is one of multiple, life‐threatening episodes of GI bleeding. We report the successful use of bevacizumab in this disease, an antibody to the vascular endothelial growth factor. Pediatr Blood Cancer 2009;52:534–536. © 2008 Wiley‐Liss, Inc.     

Heptacarpo-octatarso-dactyly combined with multiple malformations

A case of heptacarpo-octatarso-dactyly combined with cheilo-gnatho-palato-schisis, hypertelorism, macroglossia, complex malformations of heart and great vessels, horse-shoe-kidney, micro-penis, and penis palmatus is described. To our knowledge, this syndrome has not yet been described in the literature. Some of the features of the case reported overlap with syndromes such as Grauhan syndrome and Meckel syndrome.     

Polysplenia with pulmonary arteriovenous malformations

Summary A patient with polysplenia syndrome, dextrocardia, left atrial isomerism, normal great vessel relationships, and no intracardiac shunts developed progressive cyanosis and clubbing. Pulmonary arteriovenous malformations (PAVMs) were diagnosed by angiography and confirmed by lung biopsy. Superior mesenteric arteriogram revealed hypoplasia of the intrahepatic portal vein branches and a portosystemic shunt. The possible etiologies of PAVMs are discussed.     

MULTIPLE HEREDITARY GASTROINTESTINAL ATRESIAS: STUDY OF A FAMILY

ABSTRACT. Two siblings with multiple gastrointestinal atresias, from stomach to rectum, are reported. The pathological findings obtained from surgical material and complete autopsies are stressed. This syndrome, first described in 1973, presents a unique combination of clinical, radiologic and pathologic findings and is probably secondary to a malformative process taking place early in intrauterine life and effecting the whole gastrointestinal tract.     

Imerslund syndrome with dolichocephaly

Imerslund syndrome is a rare autosomal recessive disorder of megaloblastic anemia as a result of selective vitamin B12 malabsorption associated with proteinuria. An Arabic Muslim family is described, with three children who had inherited selective vitamin B12 malabsorption with proteinuria. Dolichocephaly was noted in all the male children of this family in association with congenital megaloblastic anemia and proteinuria. The findings of this anemia are compatible with Imerslund-Gr?sbeck syndrome, and coexistence of this syndrome with dolichocephaly in a single family has not been previously reported.     

Gastrointestinal Malformations Associated with Prune Belly Syndrome: Three Cases and a Review of the Literature

Prune belly syndrome (PBS), a triad consisting of abdominal musculature hypoplasia, urinary tract malformations, and cryptorchidism, is frequently associated with other congenital malformations. Although it is acknowledged that gastrointestinal (GI) malrotation and mesenteric anomalies are frequent in PBS, other GI anomalies are generally considered to be exceedingly rare. Here we describe 3 autopsy cases with severe malformations of both midgut and hindgut derivatives and review the world literature to evaluate the spectrum of GI malformations associated with this syndrome. The relatively high frequency of distal stenoses and atrcsias suggests that the anomalous mesenteric attachments may predispose to prenatal volvulus and subsequent anatomic bowel obstruction. Postnatal volvulus is also occasionally observed. Infants with PBS also appear to be at a higher risk for persistence of the common fetal cloaca.     

Respiratory distress in neonates

Respiratory distress due to either medical or surgical causes occurs commonly in neonates. It is the most common cause of admission to a neonatal surgical intensive care facility in a tertiary care hospital. The distress can be caused by a variety of clinical conditions; common conditions treated in medical intensive care units are transient tachypnea of the new born, respiratory distress syndrome, pulmonary air leak and pneumothorax. In surgical causes of respiratory distress in neonates the underlying mechanisms include airway obstruction, pulmonary collapse or displacement and parenchymal disease or insufficiency; the common causes are congenital diaphragmatic hernia, congenital cystic adenomatoid malformation, congenital lobar emphysema and esophageal atresia with or without tracheo-esophageal fistula. Obstructive lesions of the new born airway include choanal atresia, macroglossis, Pierre-Robin syndrome, lymphangioma, teratoma or other mediastinal masses, cysts, subglottic stenosis and laryngo tracheomalacia. Imaging plays a very major role in the pre-operative diagnosis of these conditions and proper pre-operative resuscitation helps in improving the results of surgery dramatically.     

Strangulation of the Umbilical Cord by Amniotic Bands: Report of 6 Cases and Literature Review

The amniotic band syndrome is the triad of amnion-denuded placenta; fetal attachment to or entanglement by amniotic remnants; and fetal deformation, malformation, or disruption. Theories of pathogenesis and etiology of the syndrome are discussed.

Amniotic bands occur in 1 of every 5000-15,000 births and are demonstrable in 1-2% of malformed infants. Nearly 10% of cases include umbilical cord strangulation. Six cases of umbilical cord strangulation by amniotic bands are presented, and 57 previously reported cases are reviewed. Two of the 63 were liveborn and 61 were stillborn, 3 of whom died intrapartum. Thirty had associated fetal abnormalities. Five were from multiple gestations. Outcome of the co-twin was determined by its presence within the same amniotic sac. Four fetuses beyond 28 weeks had short cords and were the only malformed fetuses in this age group. The earlier in gestation that amniotic bands form, the greater the likelihood of associated fetal abnormalities. All but 2 of 28 less than 32 weeks and only 4 of 35 greater than 32 weeks were malformed. A marked male predominance was noted in the former group, perhaps because the larger size and/or more vigorous movements of male fetuses promote early amnion rupture.     

Asplenia syndrome and isolated total anomalous pulmonary venous connection in siblings

We report on a family with asplenia syndrome in one and total anomalous pulmonary venous connection (TAPVC) in the other sib. Both conditions are rare, may have a genetic cause and belong to a spectrum of laterality disorders. This suggests that both asplenia syndrome and TAPVC in this family are the clinical expression of a single genetic disorder.     

Decrease in size of intrathoracic meningocele following insertion of a ventriculo-venous shunt

A nine day old boy who had the Pierre Robin syndrome also had an unusual associated hand malformation consisting of bilateral clinodactyly of the index finger. A supernumerary phalanx was inserted between the second metacarpal and the proximal phalanx of both index fingers with a radial deviation of the same phalanx. The same hand malformation has been previously described in three patients who had either the Pierre Robin syndrome or isolated cleft palate. On the basis of ours and the three previous cases, the existence of a new palato-digital syndrome is suggested.     

Oral rapamycin in the treatment of patients with hamartoma syndromes and PTEN mutation

Bannayan-Riley-Ruvacalba syndrome (BRRS) belongs to the PTEN hamartoma tumor syndromes and is characterized by a high risk of malignancy in early adulthood added to local destructive effects of hamartomas in childhood. There is no standard treatment for this condition and patients are usually offered symptomatic surgical relief. Rapamycin has been reported to be effective in the management of other conditions associated with PTEN mutation. We report here a case of BRRS in a 6-year-old male with progressive loss of function of left hand and forearm associated with pain. He was treated with oral rapamycin and regained pain-free full mobility.     

Marshall-Smith Syndrome: Report of a Case and Review of the Literature

ABSTRACT Marshall-Smith syndrome is a rare disorder characterized by accelerated skeletal maturation, bullet-shaped proximal and middle phalanges, dysmorphic facial features, and failure to thrive, and is often associated with mental retardation of variable degree. We describe an 8-month-old female with this syndrome, who has a hypoplastic corpus callosum and extreme upper airway obstruction requiring tracheostomy. Also, we review the previous reports of this syndrome since 1971 (Marshall et al., 1971).     

Phenotype heterogeneity in Gitelman's syndrome

A family with three offspring affected of Giltelman's syndrome is reported. The phenotypic variability of this entity is emphasized. Moreover, the diagnosis criteria of the syndrome, phathophysiology, and genetics and clinical differences with Bartter's syndrome are stated.