Hypoplastic Epiglottis Research Articles

Majewski Syndrome, Short Rib Polydactyly Syndrome (SRPS) Type II - A Rare Case Report, with Review of Literature

Short Rib Polydactyly Syndrome (SRPS) type II also known as Majewski syndrome, is the rarest of the four subtypes of SRPS which is a rare inherited skeletal dysplasia. We report a case of Majewski syndrome in a neonate with brief review of literature. A 24 years old primigravida, with history of second degree consanguineous marriage underwent a Prenatal USG which revealed anhydramnios, bilateral enlarged kidneys, extremely narrow thorax and bilateral short limbs with polydactyly. Based on these findings a probable diagnosis of lethal skeletal dysplasia was made and termination of pregnancy advised. Refusing termination the mother delivered a male foetus at 30 weeks with severe respiratory distress and gross anomalies. The foetus succumbed to respiratory failure inspite of resuscitation. Gross findings were a male Case Study Andola et al.; BJMMR, 9(12): 1-8, 2015; Article no.BJMMR.18367 2 foetus with enlarged head, hydropic face, hypertelorism, short nose, depressed nasal bridge, pseudo cleft lip, cleft palate, low set posterior rotated ears, cystic hygroma, micrognathia, short and narrow chest, all the limbs showed mesomelic limb shortening, postaxial polydactyly, syndactyly and brachydactyly. Postnatal X-ray, CT scan and USG confirmed the above mentioned features and additional findings were extremely short horizontal ribs and disproportionately shortened ovoid tibia. Autopsy revealed a bell shaped thorax, small hypoplastic lungs, bilateral enlarged kidneys, atrial septal defect, hypoplastic epiglottis and larynx and short small intestine. Microscopic findings of pulmonary hypoplasia, renal cystic dysplasia, hepatic fibrosis and markedly retarded endochondral ossification correlate with the clinical, radiological and pathological findings of Short Rib Polydactyly Syndrome Type II -Majewski Syndrome.

Selected genetic aspects in the pathogenesis of the thyroid diseases

According to genetic ethiopathogenesis, thyroid diseases may be divided into monogenic and polygenic (multifactorial) thyroid diseases. Monogenic thyroid diseases are the following: 1. congenital defects of thyroid hormones biosynthesis as a result of dyshormonogenetic (majority goitrous) primary congenital hypothyroidism; 2. genetic familial defects of thyroid underdevelopment, including thyroid agenesis, thyroid hypoplasia and ectopia; 3. congenital protein-binding defects, including thyroxine-binding globulin (TBG) defects, albumin and prealbumin defects; 4. congenital resistance to thyroid hormone syndrome; 5. genetic non-autoimmune hyperthyroidism; 6. medullary thyroid carcinoma (MTC) (familial type of the MTC, and multiple endocrine neoplasia MEN 2 A and B), caused by RET gene mutations and inherited as the autosomal dominant mode. About 10-15% of all cases of primary congenital hypothyroidism (CH) are associated with either a goitre or a normal thyroid gland. This type of CH has been linked to a number of defects in thyroid hormonogenesis and is caused by mutations in the following thyroid-specific genes: hNIS, Tg, TPO, PDS, THOX2, DEHAL. It is inherited by the autosomal recessive mode. Only about 2% of primary congenital hypothyroidism cases (CH) due to the defects of the thyroid underdevelopment are familial with genetic background. This type of CH is associated with mutations in genes responsible for the growth or development of thyroid follicle cells such as TSHR, TTF1, TTF2, PAX 8, NKX2, or Hoxa3. Except for defect caused by a mutation of the TSHR gene, such inborn thyroid dysgenesis is associated with an increased incidence of birth defects (such as: respiratory distress, ataxia, muscle hypotomy, choreoathetosis, cleft palate, bilateral choanal atresia, hypoplastic epiglottis, spiky hair). In addition, mutations in the GNAS 1 gene may give congenital hypothyroidism associated with hypogonadisms and Albright’s osteodystrophy, which is the part of pseudohypoparathyroidism type IA and II (pseudopseudohypoparathyroidism). The next group of monogenetic thyroid diseases with less or more evident thyroid dysfunction form the following: 1. TBG partial or complete deficiency and TBG excess due to TBG gene defects with an X-linked inheritance pattern; 2. Generalized, peripheral and pituitary resistance to thyroid hormones mainly caused by TRbeta gene mutations, inherited by the autosomal recessive. The second group of thyroid diseases are the multifactorial (polygenic) ones. Among them the most frequent are: 1. Graves’ hyperthyroidism; 2. Autoimmune thyroiditis; 3. Thyroid carcinoma derived from thyroid follicle cells such as papillary and follicular thyroid carcinoma. Although autoimmune thyroid diseases (AITD), including autoimmune thyroiditis and Graves’ hyperthyroidism with thyroid ophthalmopathy (TAO), are still unclear, they are defined as polygenic diseases resulting from genetic and environmental factors. The environmental factors which play a role in the development of AITD include iodine excess (with amiodarone treatment), selenium deficiency, stress, interferon alpha, bacterial and viral infections and, in the case of Graves’ hyperthyroidism, and tobacco smoking. There are some genes whose polymorphisms have been confirmed in the development of and susceptibility to AITD. These are the following: 1. thyroid-specific genes such as the Tg gene and 2. genes modulating the immune system, such as HLA antigens, CTLA4, PTPN22, genes encoding proinflammatory cytokines, such as: IFN, TGF beta, IL 6, IL 4, IL1 beta, IL10, and others. On the other hand, among the many genes involved in the development of differentiated thyroid carcinoma derived from thyroid follicle thyroid cells (papillary and follicular one), BRAF and RET-PTC seem to be the most important.

Craniodentofacial Manifestations in a Rare Syndrome: Orofaciodigital Type IV (Mohr-Majewski Syndrome).

Background. The orofaciodigital syndromes (OFDS) are a heterogeneous group of syndromes that affect the face, oral cavity, and the digits. OFDS type IV (OMIM %258860) is rare and characterized by broad nasal root and tip, orbital hypertelorism or telecanthus, micrognathia, hypoplastic mandible, and low-set ears. Oral symptoms may include cleft lip, cleft or highly arched palate, bifid uvula, cleft or hypoplastic maxillary and mandibular alveolar ridge, oral frenula, lingual hamartoma, and absent or hypoplastic epiglottis. Dental anomalies are common and generally include disturbances in the number of teeth. Case Report. This report presents a six-year-old girl, referred with the chief complaint of missing teeth. She was diagnosed as having OFDS type IV based on clinical findings. Her parents reported three deceased children and two fetuses that had the same phenotype. She was the seventh child of consanguineous parents who were first cousins. Conclusion. This is a very rare syndrome. Many reported OFDS type IV cases have consanguineous parents, consistent with an autosomal recessive trait. Manifestation of cleft palate in the healthy sibling may be mild expression of the disorder or an unrelated isolated cleft.

Hypoplastic Epiglottis in a Nonsyndromic Child

We describe a 2-year-old girl born out of a nonconsanguineous marriage who presented with dry cough since birth, which was often associated with feeding. She never had any choking or cyanotic/apneic spells. Her voice and cry were normal. She was born at term with no obvious congenital anomalies or perinatal problems. The child never had any other significant illness or respiratory distress to warrant hospital admission. On examination, she was a healthy-looking child without any abnormal syndromic facies or craniofacial or any other congenital anomaly. Flexible bronchoscopy done under sedation and local anesthesia revealed a rounded, short, stump-like hypoplastic epiglottis with a smooth contour. The rest of the laryngeal apparatus and the trachea-bronchial tree had normal appearance. The parents were advised to feed the child in a propped-up position and thickening of feeds to avoid aspirations. She remains well under follow-up. Hypoplastic epiglottis is a rare congenital anomaly of the upper airway, which can present with chronic cough. Endoscopic evaluation of the upper airway should be considered early in children presenting with cough associated with feeding problems.

Distraction osteogenesis and glossopexy for Robin sequence with airway obstruction

We present six cases of infants with Robin sequence and severe obstructive sleep apnoea who failed treatment with nasal mask continuous positive airway pressure (CPAP). Surgical intervention with mandibular distraction osteoneogenesis with glossopexy meant tracheostomy was avoided. Polysomnography (PSG) was used to document the severity of the obstructive sleep apnoea. The aim of this report was to assess the value of mandibular distraction osteogenesis with glossopexy in children with Robin sequence using PSG preoperatively and post-operatively. Retrospective review of medical records to assess details of preoperative clinical progress, CPAP therapy, endoscopy, PSG and respiratory parameters. Between 2003 and 2008, 20 infants with Robin sequence were admitted to the neonatal intensive care unit of our tertiary paediatric hospital. Six infants (30%) failed a treatment trial of CPAP during that period, but were subsequently successfully managed with mandibular distraction osteoneogenesis and glossopexy. At endoscopy, all had associated airway problems which included congenitally hypoplastic epiglottis (n= 2), laryngomalacia (n= 2), unilateral choanal atresia (n= 1) and long-segment tracheal stenosis (n= 1). Mandibular distraction osteogenesis with glossopexy provides relief of severe upper airway obstruction for infants with Robin sequence. Epiglottic maldevelopment was present in two infants (33%). Endoscopy and PSG assisted clinical management, but highlighted ongoing respiratory issues.

Persistent dorsal displacement of the soft palate attributable to a frenulum of the epiglottis in a racing Thoroughbred

A 7-year-old sexually intact male Thoroughbred racehorse was evaluated because of exercise intolerance, respiratory tract noise, and coughing when eating. A persistent dorsal displacement of the soft palate was identified during endoscopic examination of the upper portions of the respiratory tract. Radiography of the pharyngeal and laryngeal regions revealed a hypoplastic epiglottis that was ventral to, and not in contact with, the soft palate. The horse was anesthetized, and an oral endoscopic examination revealed a subepiglottic frenulum that had resulted in the dorsal displacement of the soft palate. The frenulum was transected transendoscopically by use of a diode laser. Twenty-four hours following surgery, repeat endoscopic and radiographic examinations revealed that the epiglottis had returned to its correct anatomic position in relation to the soft palate. Four weeks after surgery, endoscopy of the upper portions of the airway revealed recurrence of the dorsal displacement of the soft palate. A subepiglottic frenulum should be considered as a cause of persistent dorsal displacement of the soft palate in horses. An endoscopic examination of the oropharyngeal region should be performed in horses prior to undertaking any surgical interventions to treat persistent dorsal displacement of the soft palate.

Correlation of performance with endoscopic and radiographic assessment of epiglottic hypoplasia in racehorses with epiglottic entrapment corrected by use of contact neodymium:yttrium aluminum garnet laser

Summary Epiglottic entrapment in 35 Thoroughbred and 44 Standardbred horses was corrected transendoscopically by use of a neodymium:yttrium aluminum garnet laser. Before surgery, the entrapped epiglottis was classified as hypoplastic or normal in each horse on the basis of endoscopic appearance alone. Using a digitizer, thyroepiglottic length was determined from lateral-view laryngeal radiographs. For 78 racehorses, earnings (<$5,000 or >$5,000) were compared before and after surgery. Earnings category and racing performance after surgery were tested for association with endoscopically determined epiglottic hypoplasia and radiographically determined thyroepiglottic length. Endoscopy and radiography were useful methods of evaluating the epiglottis in horses with epiglottic entrapment. Mean (±sd) thyroepiglottic length for both breeds of horses with epiglottic entrapment was significantly (P = 0.0001) smaller (Thoroughbreds, 7.28 ± 0.67 cm; Standardbreds, 7.21 ± 0.62 cm), compared with thyroepiglottic length measured from control groups composed of clinically normal Thoroughbred (8.56 ± 0.29 cm) and Standardbred (8.74 ± 0.38 cm) racehorses. Both breeds of horses with epiglottic entrapment that had endoscopically apparent hypoplastic epiglottis had significantly (P < 0.0001) smaller thyroepiglottic length (Thoroughbreds, 6.64 ± 0.60 cm; Standardbred, 6.93 ± 0.72 cm) than did horses with epiglottic entrapment that had endoscopically normal epiglottis (Thoroughbreds, 7.57 ± 0.47 cm, Standardbreds, 7.36 ± 0.50 cm). Significant difference was not detected in endoscopic appearance of the epiglottis among age, gender, or breed distributions. For either breed, earnings and performance were not significantly associated with endoscopically determined epiglottic hypoplasia or radiographically determined thyroepiglottic length. Prognosis for racing performance after laser correction of epiglottic entrapment should be based on assessment of the endoscopic and radiographic appearances of the epiglottis, pharynx, and larynx, determination of thyroepiglottic length, and a knowledge of the horse's earnings and racing performance prior to surgery.

Transendoscopic contact neodymium:yttrium aluminum garnet laser correction of epiglottic entrapment in standing horses

Summary Fifty-seven Standardbred and 44 Thoroughbred racehorses and 1 Thoroughbred polo mare with primary clinical signs of exercise intolerance or respiratory tract noise or combined exercise intolerance and respiratory tract noise were referred for laser correction of epiglottic entrapment. Significantly (P < 0.001) more Standardbred than Thoroughbred racehorses were affected, compared with the observed hospital population during the same period. At referral, 14 horses did not have evident epiglottic entrapment and were returned to exercise without development of entrapment after treatment, which consisted of 1 week of rest and administration of anti-inflammatory medication. In 88 standing horses under sedation and topical anesthesia, epiglottic entrapment was corrected transendoscopically by use of a contact neodymium:yttrium aluminum garnet laser. In these 88 horses, 98% of entrapments were persistent, 92% were thick, 97% were wide, and 45% were ulcerated. Thirty-one percent of the horses had endoscopic evidence of epiglottic hypoplasia, and 8% had deviated epiglottic axis. Complete correction was achieved in 97% of the horses, Persistent dorsal displacement of the soft palate in 1 horse and severe epiglottic hypoplasia with thick, chronic entrapping membranes in 2 horses precluded successful transendoscopic correction with the horses in standing position. Most horses were treated onan outpatient basis, and all were able to be returned to exercise after 7 to 14 days of rest and treatment with anti-inflammatory medication. Entrapment recurred in 4 horses (5%), 3 of which had hypoplastic epiglottis. Dorsal displacement of the soft palate developed after surgery in 9 horses (10%) and continued in 4 horses (5%) that had displaced soft palate before surgery. All these horses had epiglottic hypoplasia. Laser correction of epiglottic entrapment in standing horses was safe, well tolerated, and effective. Laser surgery was an alternative to conventional surgery, and eliminated the need for general anesthesia and laryngotomy. It also reduced convalescence and postoperative complications.

THE MOHR AND MAJEWSKI SYNDROMES: OVERLAPPING PHENOTYPES

The Mohr syndrome (oral-facial-digital syndrome, type II) and the Majewski syndrome (a form of short rib-polydactyly) are currently described as separate dysmorphic syndromes with autosonal recessive inheritance. The Mohr syndrome is characterized by median cleft of the upper lip, cleft tongue, oral hamartomas, bimanual polydactyly, hallucal reduplication and a normal lifespan. The Majewski syndrome is characterized by cleft lip, hypoplastic epiglottis, short ribs, genitourinary anomalies, mesomelic brachymelia, pre- and postaxial polydactyly and death in infancy.We studied two unrelated female infants with features common to both syndromes. One had median pseudocleft of the upper lip, lingual nodules, short ribs, urogenital sinus, hydrometrocolpos, short tibias and hallucal reduplication. She failed to thrive and died at 4 months of age. The second infant had median pseudocleft of the upper lip, lingual nodules, micrognathia, epiglottic hypoplasia, pre- and postaxial polydactyly and hallucal reduplication. Despite tracheostomy, she died at 11 months of age. On post-mortem exam a single atrium and ventricular septal defect were found. Both infants had orofacial and digital features typical of the Mohr syndrome. However, one had the skeletal and genitourinary abnormalities and the other, the hypoplastic epiglottis of the Majewski syndrome. The presence in our patients of anomalies typical of the Mohr and Majewski syndromes may indicate that these syndromes represent two extremes of the same disorder.