Hereditary neuralgic amyotrophy: a paediatric and familial presentation of Parsonage-Turner syndrome.]

Hereditary neuralgic amyotrophy is a rare disorder, characterized by recurrent attacks of pain in a brachial plexus distribution. We report the case of a 12-year-old boy with several attacks of pain and atrophy of the muscles of the shoulders. The age of onset of this disease is variable, most frequently in the second or third decade. Pediatric onsets, during the first decade are rare. The differences between the hereditary neuralgic amyotrophy and the sporadic Parsonage-Turner syndrome are painful recurrent episodes of weakness and similar familial cases. The analysis of several families has shown that hereditary neuralgic amyotrophy phenotype is heterogeneous and two different clinical courses can be discerned. Recent evidence indicates that HNA is genetically heterogeneous. Pathophysiology of the disease remains unclear, so the treatment is not clearly established.     

Familial vocal cord dysfunction

Vocal cord paralysis is a common cause of neonatal stridor. Familial vocal cord dysfunction, however, is unusual. All three siblings in one family had neonatal stridor. Vocal cord dysfunction was confirmed after endoscopic examination in two of the children; a temporary tracheotomy was required by one child. Results of evaluation, including pulmonary function tests, suggest discrete dysfunction localized to the neuromuscular pathway responsible for vocal cord abduction. Endoscopy is of prime importance in the diagnosis of vocal cord dysfunction. In considering therapy, the physician must weigh both the potentially life-threatening nature of vocal cord paralysis, as well as the likelihood of eventual spontaneous resolution of many familial and idiopathic cases.     

Stridor: intracranial pathology causing postextubation vocal cord paralysis

During an 18-month period in a pediatric intensive care unit, nine patients with vocal cord paralysis were identified using flexible bronchoscopy. When tracheally extubated, each child was found to have stridor. The children ranged in age from 17 days to 5 1/2 years. Two patients had unilateral paralysis, but neither required tracheostomy. Seven patients displayed bilateral abductor vocal cord paralysis. Of these, six patients required tracheostomy. Surgical injury to the recurrent laryngeal nerve was the probable cause in two patients. The other seven patients had neurologic disorders with documented or suspected increases of intracranial pressure. Four of the seven patients with bilateral abductor vocal cord paralysis regained cord mobility within 4 months. Both children with unilateral cord paralysis have no stridor and vocalize well 1 year later. Cord paralysis in the setting of intracranial hypertension probably results from compression or ischemia of the vagus nerve before it exits the skull. Early visualization of the larynx should be done in patients who become stridulous when extubated, especially those with prior thoracic procedures or with neurologic disorders associated with intracranial hypertension.     

Neonatal vocal cord paralysis following extracorporeal membrane oxygenation

Five cases of unilateral vocal cord paralysis/paresis were diagnosed following extracorporeal membrane oxygenation for newborn respiratory failure. All were right sided and transient in nature. None of the five patients had other findings commonly associated with vocal cord palsy. The extracorporeal membrane oxygenation procedure requires surgical dissection in the carotid sheath on the right side of the neck, an area immediately adjacent to both the vagus and recurrent laryngeal nerve. It is speculated that vocal cord paralysis in these infants was acquired as a result of the extracorporeal membrane oxygenation cannulation. Although the vocal cord paralysis resolved in all cases, two patients had difficult courses after extracorporeal membrane oxygenation. Therefore, laryngoscopic examination should be considered for patients after extracorporeal membrane oxygenation.     

Age of onset in hereditary lymphedema

OBJECTIVE: To characterize age of onset patterns and penetrance in hereditary lymphedema, including differences caused by sex and genetic heterogeneity. STUDY DESIGN: Kaplan-Meier analysis of three family cohorts with autosomal dominant lymphedema: (1) five families with unique mutations in FLT4, (2) 16 families with unique mutations in FOXC2, and (3) 77 families with no mutations yet identified in any gene (the heterogeneous group). RESULTS: Age of onset was typically congenital among FLT4 mutation families and pubertal among FOXC2 mutation families, with similar male and female penetrance in both groups. Age of onset was highly variable in the families with no identified mutation, with substantially higher penetrance among female patients than male patients. In addition, male patients and female patients in the heterogeneous group had very different overall age of onset profiles. CONCLUSIONS: The two genes identified to date that cause hereditary lymphedema have equal male and female effects, but each displays a different pattern of onset age and penetrance. The heterogeneous group represents a genetically heterogeneous population and has phenotypic overlaps with the FLT4 and FOXC2 mutation families.     

Ductus aneurysm as a rare cause of inspiratory stridor in the newborn infant

A paralysis of the left vocal cord was seen by laryngoscopy in a 3-days-old boy with inspiratory stridor. A ductus aneurysm was established by angiocardiography, which was believed to be the cause of the vocal cord paralysis. Within 8 days after the angiocardiography the aneurysm became smaller and the stridor disappeared. Twelfth months later the control-angiocardiography showed the total obliteration of the ductal aneurysm.     

Neonatal vocal cord palsy. Clinical and therapeutical approaches

Between 1998 and 2000, four newborns have been observed for laryngeal stridor occurred some hours after birth. Otorhinolaryngologic examinations, as well as cardiac, neuroradiologic and serologic investigations have been performed to formulate the diagnosis and verify the etiology. The fiberoptic laryngoscopy showed a bilateral paralysis of the vocal cord in two newborns, a monolateral paralysis of the left vocal cord in another and in the last one, instead, a bilateral cordal hypomobility. The follow-up performed till the age of one year showed a complete remission of the symptomatology in two newborns, respectively in the one with monolateral paralysis and in the other affected by hypomobility of the vocal cords; of the two newborns with bilateral paralysis, instead, one is dead because of Haemophilus Influenzae epiglottitis, three weeks after discharge without physicians' consensus, while in the other patient, affected by lobar holoprosencephaly, it was necessary to perform a tracheotomy because of a severe obstructive apnea. The lobar holoprosencephaly, is a cerebral malformation characterized by the partial separation of the cerebral hemispheres, and it is described for the first time associated with bilateral vocal cords paralysis.     

Vocal cord paralysis secondary to impacted esophageal foreign bodies in young children

Impacted foreign bodies in the esophagus can result in respiratory symptoms including stridor and aphonia. Several mechanisms have been proposed to explain these symptoms, but the possibility of vocal cord paralysis and its cause has not been adequately emphasized. Two cases of young children with esophageal foreign body are described; both presented with respiratory symptoms, 1 with aphonia and the other with stridor. In both cases, the symptoms were secondary to vocal cord paralysis. A possible mechanism of recurrent nerve injury is proposed.     

Treatment for neonatal neuralgic amyotrophy

We report a 15-day-old neonate with a brachial plexus neuropathy diagnosed as neuralgic amyotrophy concomitant with an osteomyelitis of the ipsilateral humerus. She was treated with intravenous antibiotics and oral dexamethasone and improved dramatically within days.     

遗传性远端肾小管酸中毒的临床特点和SLC4A1基因突变分析

目的研究两个原发性远端肾小管酸中毒(d RTA)家系的临床特征和致病基因SLC4A1突变情况。方法通过家系调查、病史采集和生化指标检测,分析d RTA临床表型和遗传特点。通过直接测序法检测SLC4AI基因突变。结果两个家系共有3例患者(其中两例为母子)确诊为d RTA,均有显著的临床特征,包括身材矮小、代谢性酸中毒、碱性尿、低钾血症和肾脏钙盐沉积。SLC4A1基因分析证实3例患者均存在致病性错义突变R589H(c.1766GA)。家系1的患儿为SCL4A1的新生突变,家系2患儿的SLC4A1基因突变遗传自其母,符合常染色体显性遗传特点。结论本研究首次在国内报道遗传性d RTA家系中SLC4A1基因R589H突变。对疑似遗传性d RTA患者进行基因检测可提高早期诊治率。     

A new DAX-1 mutation in a family with a case of neonatal adrenal insufficiency and a sibling with adrenal hypoplasia and sudden death at 3 years of age

Adrenal hypoplasia congenita (AHC) is a hereditary disorder that leads to adrenal insufficiency and hypogonadotropic hypogonadism (HHG) in childhood. The gene responsible for the X-linked form of AHC, DAX1 (dosage-sensitive sex-reversal, AHC, on the X-chromosome, gene 1)/NR0B1, encodes for a nuclear factor which lacks the characteristic zinc finger DNA-binding domain that is highly conserved in nuclear receptors. Deletions and point mutations in the DAX1 gene have been described in more than 70 AHC families. We present the clinical and genetic data of two brothers affected by AHC. We report a new DAX1 gene mutation in a family with two affected members: one with neonatal adrenal insufficiency, and a sibling with adrenal hypoplasia and sudden death at 3 years old. The NR0B1/DAX1 gene was amplified in three PCR fragments from the patient's and mother's gDNA extracted from peripheral lymphocytes. Sequencing revealed a novel single nucleotide deletion in codon 419 from exon 2 that resulted in a frameshift and a stop codon 17 nucleotides downstream (c.1256 delA). The mother was heterozygous for this mutation. In conclusion, a novel DAX-1 mutation was detected in two family members with different phenotype: one live infant with adrenal hypoplasia, his mother, and probably his dead brother.     

Respiratory obstruction and apnea in infants with bilateral abductor vocal cord paralysis, meningomyelocele, hydrocephalus, and Arnold-Chiari malformation

This report describes 21 infants and children with bilateral abductor vocal cord paralysis and associated meningomyelocele, Arnold-Chiari malformation, and hydrocephalus. Two life-threatening forms of respiratory distress are distinguished: (1) upper airway obstruction due to bilateral abductor cord paralysis and (2) apnea. Clinically significant episodes of apnea were documented in 13 infants. Ten infants had evidence of aspiration and dysphagia. Vocal cord paralysis, apnea, aspiration, and dysphagia were frequently temporally related to increased intracranial pressure.     

Vocal cord paralysis in neuraxial malformation

Vocal cord paralysis can occur in children bom with spina bifida cystica who may have Arnold-Chiari malformation and hydrocephalus. Two cases are reported to illustrate this. In one, the vocal cord paralysis was of the bilateral abductor type and was due, most probably, to primary brainstem disease. In the other, vagal involvement and brainstem dysgenesis seem to operate in combination to cause a unilateral paramedian cord paralysis. Relevant literature is briefly reviewed.     

Stridor and airway compromise

A graduated approach to the diagnosis of airway lesion will rarely fail. The availability of state-of-the-art optical equipment, excellent anesthesia, and high-quality medical care have remarkably reduced the morbidity and mortality of airway diseases. Electrodiagnosis of vocal cord paralysis will differentiate fixed arytenoids from neurogenic paralysis in candidates for laryngeal repair and will help define the prognosis of neurogenic paralysis. The excellent results from epiglottoplasty in treating laryngomalacia and laryngotracheal reconstruction for stenosis make obsolete any management with tracheotomy and watchful waiting. Close cooperation and good communication between the pediatrician and the otolaryngologist remain the key points for successful management.     

Distal arthrogryposis: clinical and genetic findings

Aim: Distal arthrogryposis is characterized by congenital contractures predominantly in hands and feet. Mutations in sarcomeric protein genes are involved in several types of distal arthrogryposis. Our aim is to describe clinical and molecular genetic findings in individuals with distal arthrogryposis and evaluate the genotype‐phenotype correlation. Method: We investigated 39 patients from 21 families. Clinical history, including neonatal findings, joint involvement and motor function, was documented. Clinical examination was performed including evaluation of muscle strength. Molecular genetic investigations were carried out in 19 index cases. Muscle biopsies from 17 patients were analysed. Results: A pathogenic mutation was found in six families with 19 affected family members with autosomal dominant inheritance and in one child with sporadic occurrence. In three families and in one child with sporadic form, the identified mutation was de novo. Muscle weakness was found in 17 patients. Ambulation was affected in four patients and hand function in 28. Fourteen patients reported pain related to muscle and joint affection. Conclusion: The clinical findings were highly variable between families and also within families. Mutations in the same gene were found in different syndromes suggesting varying clinical penetrance and expression, and different gene mutations were found in the same clinical syndrome demonstrating genetic heterogeneity.     

西北地区751例新生儿耳聋基因突变筛查

目的初步了解西北地区新生儿常见耳聋基因突变类型和携带率,探讨耳聋基因突变筛查对于辅助诊断和防治新生儿遗传性耳聋的临床价值。方法采集西北地区751例新生儿的足跟血,采用15项遗传性耳聋基因检测试剂盒(微阵列芯片法)对中国人群常见4种耳聋基因15个突变位点进行筛查。结果在751例新生儿中,检测到39例新生儿携带耳聋基因突变,总突变携带率为5.18%。其中GJB2基因突变19例,突变携带率为2.53%;SLC26A4基因突变16例,突变携带率为2.12%;线粒体12SrRNA 1555A>G均质突变4例,突变携带率为0.53%。新疆出生的新生儿279例中,检测到耳聋基因突变11例,突变携带率3.95%;甘肃省出生的新生儿277例中,检测到耳聋基因突变12例,突变携带率4.32%;陕西省出生的新生儿178例中,检测到耳聋基因突变12例,突变携带率6.74%;青海省出生的新生儿17例中,检测到耳聋基因突变4例,突变携带率23.52%。结论西北地区新生儿耳聋基因突变携带率偏高,但是GJB2基因235 del C位点的突变携带率偏低,可能与西北地区的地域特征和人口遗传学特点有关。新生儿耳聋基因筛查对于听力筛查具有很好的互补作用,可以从基因水平发现可能出现迟发性耳聋和药物敏感性耳聋的高危新生儿。     

Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott–Rallison syndrome

Wolcott–Rallison syndrome (WRS), caused by mutation in the EIF2AK3 gene encoding the PERK enzyme, is the most common cause of permanent neonatal diabetes mellitus (PNDM) in consanguineous families and isolated populations. Besides PNDM, it also includes skeletal abnormalities, liver and renal dysfunction, and other inconsistently present features. We present two siblings, who are WRS patients, and are Albanians from Kosovo born to unrelated parents. The older sister presented with PNDM, exocrine pancreatic insufficiency, short stature, microcephaly, normocytic anemia, delay in speech development, skeletal abnormalities, primary hypothyroidism, and hypoplastic nipples. Sequencing of the EIF2AK3 gene identified a homozygous mutation R902X in exon 13. The younger brother was diagnosed with PNDM and died from hepatic failure suggesting that he has been suffering from WRS as well. Including one previously reported patient from Kosovo carrying the same homozygous mutation, there are three WRS patients from this very small, ethnically homogenous region suggesting founder effect in this population. Conclusion: We postulate that thyroid hypoplasia with primary subclinical hypothyroidism already reported in two WRS patients and nipple hypoplasia could also be the phenotypic reflection of the mutation of pleiotropic EIF2AK3 gene in secretory cells.     

遗传性果糖不耐受1例及其父母常见基因突变检测

目的检测1例中国人的常染色体隐性遗传的遗传性果糖不耐受患儿及其父母的3种最常见致病基因。方法对2006年3月于吉林大学第二医院儿科就诊的疑患遗传性果糖不耐受的患儿进行了尿代谢产物分析,采集患儿及其父母外周血,提取全基因组DNA,使用等位基因特异性寡核苷酸分析法检测了A149P、A174D和N334K这3种最常见的基因突变。结果患儿临床诊断为遗传性果糖不耐受,进行PCR扩增,等位基因特异性寡核苷酸分析法显示患儿及其父母的A149P、A174D和N334K均为阴性。结论结合临床资料及尿中代谢产物分析,可以在临床上确诊遗传性果糖不耐受。PCR结合等位基因特异性寡核苷酸分析可用于遗传性果糖不耐受病例的基因诊断,中国人群中遗传性果糖不耐受的基因突变分型有待于进一步探索。     

The upper airway: congenital malformations

The upper airway extends from the nasal aperture to the subglottis and can be the site of multiple types of congenital malformations leading to anatomical or functional obstruction. This can cause severe respiratory distress. Newborns are obligate nasal breathers; therefore nasal obstruction can lead to airway compromise and respiratory distress. The etiologies are varied and include, choanal atresia, pyriform aperture stenosis, and rarely tumors such as glioma, encephalocele, teratoma, or dermoid. More common upper airway congenital anomalies include laryngomalacia, vocal cord paralysis, and subglottic stenosis. Laryngolmalacia is the most common congenital laryngeal anomaly. Inspiratory stridor often does not present until two weeks after birth and resolves by 18 months of age. Most cases are managed with watchful waiting. Severe cases require a surgical intervention. Bilateral vocal cord paralysis is usually idiopathic. In certain cases, paralysis may occur secondary to central nervous system abnormality including Arnold-Chiari malformation, cerebral palsy, hydrocephalus, myelomeningocele, spina bifida, or hypoxia. Severe cases may necessitate endotracheal intubation and tracheostomy. Congenital subglottic stenosis is the third most common laryngeal anomaly. It is defined as a diameter of less than 4mm of the cricoid region in a full-term infant, and less than 3mm in a premature infant. This condition is the most common laryngeal anomaly that requires tracheotomy in newborns. Laryngotracheoplasty may be required to achieve decanulation. Knowledge of the upper airway embryological development and congenital anomalies is off prime importance in assessing the newborn with respiratory distress. In most cases flexible endoscopy establishes the diagnosis. Management is tailored to each condition and its degree of severity.     

Recurrent laryngeal nerve monitoring during thyroid surgery in childhood.

INTRODUCTION: Diseases of the thyroid gland are one of the most common endocrinopathies in childhood. Neither benign nor malignant thyroid diseases are often treated surgically. But if surgical treatment is carried out, intraoperative damage of the recurrent laryngeal nerve (RLN) is a common and severe complication. In adult surgery, therefore, intraoperative monitoring (IOM) of the RLN is a method which has been used since several years. The question is whether this method can be used in paediatric surgery for the identification and functional control of the integrity of the RLN. METHODS: Surgical treatment of benign (9 x) or malignant (1 x) thyroid diseases was performed in ten children (median age: 13 years) with 16 nerves at risk (NAR). The function of the vocal cord was controlled in all children before and after surgery. Intraoperative identification and functional control of the recurrent nerve was performed using the Neurosign 100, placing a needle electrode transligamentously into the vocal muscle. All results before and after resection were documented. RESULTS: A clear and reliable identification of the RLN was possible in all cases. All NAR showed a constant physiological nerve signal before and after surgical resection of the thyroid gland. However in one young patient the postoperative control of the vocal cord revealed a partial paralysis despite the constant intraoperative signal of the RLN. The control on this patient after a period of six months showed a normal function. CONCLUSION: IOM of the RLN as used in adult surgery could easily be used in paediatric surgery as well. A clear and positive identification of the RLN was possible in all these patients. Therefore, IOM of the RLN could develop into a helpful and easy method for the prevention of intraoperative damage of the recurrent laryngeal nerve during thyroid surgery in childhood.