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Laryngoscope ; 131(12): 2811-2816, 2021 12.
Article En | MEDLINE | ID: mdl-34117782

OBJECTIVES/HYPOTHESIS: Robin sequence (RS) consists of associated micrognathia, glossoptosis, and respiratory dysfunction, with or without cleft palate. Studies on how different patient characteristics impact the severity of respiratory dysfunction are scarce and contradictory; this study investigates how different features affect respiratory obstruction severity at diagnosis of RS in controlled analysis. STUDY DESIGN: Retrospective cohort study that enrolled 71 RS patients under 90 days old who received care in our institution from 2009 to 2020. METHODS: The primary outcome, respiratory dysfunction, was categorized into four severity groups and analyzed using a multinomial logistic regression model that considered age, sex, mandible length, cleft palate, syndromic diagnosis, other airway anomalies, and degree of glossoptosis. RESULTS: Mandible length, syndromic diagnosis, and Yellon grade 3 glossoptosis were related to poorer respiratory outcomes (need for respiratory support). In univariate analysis, for each additional 1 mm of mandible length at diagnosis, a mean reduction of 28% in the risk of needing respiratory support was observed (OR = 0.72; 0.58-0.89); syndromic diagnosis and grade 3 glossoptosis also raised the risk (OR = 6.50; 1.59-26.51 and OR = 12.75; 1.03-157.14, respectively). In multivariate analysis, only mandible length significantly maintained its effects (OR = 0.73; 0.56-0.96), a 27% reduction. CONCLUSIONS: Mandible length was an independent predictor for more severe respiratory dysfunction in RS patients, with larger mandibles showing protective effects. Syndromic diagnosis and Yellon grade 3 glossoptosis are also likely to be associated with poorer respiratory outcomes, although this was not demonstrated in multivariate analysis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2811-2816, 2021.

Glossoptosis/complications , Pierre Robin Syndrome/complications , Respiration Disorders/epidemiology , Female , Glossoptosis/diagnosis , Glossoptosis/pathology , Humans , Imaging, Three-Dimensional , Infant , Infant, Newborn , Male , Mandible/diagnostic imaging , Mandible/pathology , Organ Size , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/pathology , Prognosis , Protective Factors , Respiration Disorders/diagnosis , Respiration Disorders/etiology , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed
Muscle Nerve ; 63(4): 516-524, 2021 04.
Article En | MEDLINE | ID: mdl-33389762

INTRODUCTION: Congenital facial weakness (CFW) can result from facial nerve paresis with or without other cranial nerve and systemic involvement, or generalized neuropathic and myopathic disorders. Moebius syndrome is one type of CFW. In this study we explored the utility of electrodiagnostic studies (EDx) in the evaluation of individuals with CFW. METHODS: Forty-three subjects enrolled prospectively into a dedicated clinical protocol and had EDx evaluations, including blink reflex and facial and peripheral nerve conduction studies, with optional needle electromyography. RESULTS: MBS and hereditary congenital facial paresis (HCFP) subjects had low-amplitude cranial nerve 7 responses without other neuropathic or myopathic findings. Carriers of specific pathogenic variants in TUBB3 had, in addition, a generalized sensorimotor axonal polyneuropathy with demyelinating features. Myopathic findings were detected in individuals with Carey-Fineman-Ziter syndrome, myotonic dystrophy, other undefined myopathies, or CFW with arthrogryposis, ophthalmoplegia, and other system involvement. DISCUSSION: EDx in CFW subjects can assist in characterizing the underlying pathogenesis, as well as guide diagnosis and genetic counseling.

Facial Paralysis/congenital , Facial Paralysis/diagnosis , Mobius Syndrome/diagnosis , Muscular Diseases/diagnosis , Pierre Robin Syndrome/diagnosis , Adult , Diagnosis, Differential , Facial Paralysis/genetics , Facial Paralysis/physiopathology , Female , Heterozygote , Humans , Male , Mobius Syndrome/genetics , Mobius Syndrome/physiopathology , Muscular Diseases/genetics , Muscular Diseases/physiopathology , Mutation/genetics , Pierre Robin Syndrome/genetics , Pierre Robin Syndrome/physiopathology
Laryngoscope ; 131(7): 1647-1651, 2021 07.
Article En | MEDLINE | ID: mdl-33300625

OBJECTIVES/HYPOTHESIS: The anatomy of children with severe Pierre Robin sequence can present a challenge for direct laryngoscopy and intubation. Advanced techniques including flexible fiberoptic laryngoscopic intubation have been described but require highly specialized skill and equipment. Rigid video laryngoscopy is more accessible but has not been described in this population. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective review was completed at a tertiary care center of all children between January 2016 and March 2020 with Pierre Robin sequence who underwent a mandibular distraction osteogenesis procedure. Intubation events were collected, and a descriptive analysis was performed. A univariate logistic regression model was applied to direct laryngoscopy and flexible fiberoptic laryngoscopy with rigid video laryngoscopy as a reference. RESULTS: Twenty-five patients were identified with a total of 56 endotracheal events. All patients were successfully intubated. Direct laryngoscopy was successful at first intubation attempt in 47.3% (9/19) of events. Six direct laryngoscopy events required switching to another device. Rigid video laryngoscopy was successful at first intubation attempt in 80.5% (29/36) of events. Two cases required switching to another device. Flexible fiberoptic laryngoscopy was found successful at first intubation attempt in 88.9% (8/9) of events. Direct laryngoscopy was 4 times more likely to fail first intubation attempt when compared to rigid video laryngoscopy (P < .05). There was no significant difference between rigid video laryngoscopy and flexible fiberoptic laryngoscopy for intubation. CONCLUSIONS: For children with Pierre Robin sequence rigid video laryngoscopy should be considered as a first attempt intubation device both in the operating room and for emergent situations. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1647-1651, 2021.

Airway Obstruction/surgery , Intubation, Intratracheal/methods , Laryngoscopy/methods , Pierre Robin Syndrome/complications , Adolescent , Airway Obstruction/etiology , Child , Child, Preschool , Equipment Failure , Female , Humans , Infant , Infant, Newborn , Intubation, Intratracheal/instrumentation , Laryngoscopes , Laryngoscopy/instrumentation , Male , Mandible/abnormalities , Mandible/surgery , Osteogenesis, Distraction , Pierre Robin Syndrome/diagnosis , Retrospective Studies , Severity of Illness Index , Treatment Outcome
Medicine (Baltimore) ; 99(45): e23033, 2020 Nov 06.
Article En | MEDLINE | ID: mdl-33157955

INTRODUCTION: Microdeletion syndromes occur from deletion of 5Mb of a chromosome in approximately 5% of patients with unexplained intellectual disability. Interstitial microdeletions at bands 1p33 and 1p32.2 of the short arm of chromosome 1 are rare and have not been previously reported in relation to disease. PATIENT CONCERNS: We present a case of a 39-month boy with Pierre Robin sequence, development delay/intellectual disability, growth retardation, short stature, leukoencephalopathy, craniofacial dysplasia, and speech delay. The child was referred to the Child health care department in October 2014 for his delayed language development and aggravated aggression. DIAGNOSIS: Molecular diagnostic testing with G-band karyotyping was normal but clinical microarray analysis detected a 10 Mb microdeletion at 1p33p32.2. INTERVENTIONS: The patient received rehabilitation. OUTCOMES: Three candidate genes were pinpointed to the deleted area, including ORC1, SCP2, and DAB1. Phenotype-genotype analysis suggested that these three genes are likely to be responsible for the main phenotypes observed in the patient, such as microcephaly, growth retardation, short stature, leukoencephalopathy, and development delay/intellectual disability. CONCLUSIONS: The spectrum of phenotypes this case presented with are likely to be caused by 1p33p32.2 deletion which could represent a new microdeletion syndrome.

Karyotyping/methods , Microarray Analysis/methods , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Adaptor Proteins, Signal Transducing/genetics , Adolescent , Adult , Carrier Proteins/genetics , Child , Child, Preschool , Chromosome Deletion , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/genetics , Dwarfism/diagnosis , Dwarfism/genetics , Female , Humans , Infant , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Language Development Disorders/diagnosis , Language Development Disorders/genetics , Leukoencephalopathies/diagnosis , Leukoencephalopathies/genetics , Male , Microcephaly/diagnosis , Microcephaly/genetics , Nerve Tissue Proteins/genetics , Origin Recognition Complex/genetics , Phenotype , Pierre Robin Syndrome/rehabilitation
Acta Medica (Hradec Kralove) ; 63(2): 86-90, 2020.
Article En | MEDLINE | ID: mdl-32771075

Pierre Robin sequence (PRS) is characterized by the triad of retrognathia, glossoptosis, and airway obstruction. PRS may occur in isolation or in conjunction with other syndromes. Distinguishing isolated and syndromic forms of PRS helps clinicians decide the management plan. We describe two cases of PRS of Indian ethnicity and describe some of the difficulties that we faced while distinguishing isolated PRS from syndromic PRS. Both cases had a similar clinical presentation. However, one of the cases had a positive family history of congenital deafness and cleft palate, whereas the other case had apparent upper limb anomalies. These facts heightened the suspicion of an associated syndrome. However, based on the available facts and after thorough investigations, a tentative diagnosis of isolated PRS was made for both the patients. Both the cases were managed conservatively and were advised a long-term follow-up. When the associated anomalies are few, minor or concealed at birth, longitudinal follow-up of all PRS cases combined with thorough diagnostics including chromosomal analysis could help differentiate syndromic PRS from isolated PRS. Regardless, all cases of PRS require a multidisciplinary approach.

Pierre Robin Syndrome/diagnosis , Humans , Infant , Infant, Newborn , Male , Pierre Robin Syndrome/complications , Prone Position , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
J Neuromuscul Dis ; 7(3): 309-313, 2020.
Article En | MEDLINE | ID: mdl-32333597

Carey-Fineman-Ziter syndrome is a congenital myopathy associated with mutations in the MYMK gene. It is clinically defined by the combination of hypotonia, Moebius-Robin sequence, facial anomalies and motor delay. Historically it was considered a brainstem dysgenesis syndrome. We provide detailed information of a Spanish boy with compound heterozygous variants in MYMK gene. A muscle biopsy performed as a toddler only disclosed minimal changes, but muscle MRI showed severe fatty infiltration of gluteus muscles and to a lesser extent in adductors magnus, sartorius and soleus muscles. Clinical course is fairly static, but the identification of new well characterized genetic cases will help to delineate the complete phenotype.

Membrane Proteins/genetics , Mobius Syndrome/diagnosis , Mobius Syndrome/genetics , Mobius Syndrome/pathology , Muscle Proteins/genetics , Muscular Diseases/diagnosis , Muscular Diseases/genetics , Muscular Diseases/pathology , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/genetics , Pierre Robin Syndrome/pathology , Brain Diseases/diagnosis , Brain Stem/abnormalities , Child , Diagnosis, Differential , Humans , Male
Int J Pediatr Otorhinolaryngol ; 130: 109855, 2020 Mar.
Article En | MEDLINE | ID: mdl-31896499

OBJECTIVE: To provide recommendations for the comprehensive management of airway obstruction in patients with Robin Sequence. METHODS: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). RESULTS: The consensus statement provides recommendations for medical specialists who manage infants with Robin Sequence including: evaluation and treatment considerations for commonly debated issues in post-natal airway obstruction, assessment of antenatal obstruction and perinatal airway management. CONCLUSION: Consensus recommendations are aimed at improving management of airway obstruction in patients with Robin Sequence.

Airway Obstruction/therapy , Pierre Robin Syndrome/therapy , Airway Management , Airway Obstruction/diagnosis , Airway Obstruction/etiology , Consensus , Female , Humans , Infant , Infant, Newborn , Male , Otolaryngology , Pierre Robin Syndrome/complications , Pierre Robin Syndrome/diagnosis , Practice Guidelines as Topic
Am J Med Genet A ; 182(3): 431-436, 2020 03.
Article En | MEDLINE | ID: mdl-31769200

Catel-Manzke syndrome, also known as micrognathia-digital-syndrome, is a rare autosomal recessive disorder characterized by the combination of the two cardinal features Pierre-Robin sequence and bilateral hyperphalangy leading to ulnar clinodactyly (ulnar curvature of the phalanges) and radial deviation (radial angulation at the metacarpophalangeal joint) of the index fingers. Individuals without one of these major hallmarks or with additional hand malformations have been described as atypical or Catel-Manzke-like syndrome. Biallelic TGDS pathogenic variants have thus far been detected in eight individuals with typical Catel-Manzke syndrome and in one fetus with additional features. Here we report on two individuals with TGDS pathogenic variants who presented with mild radial deviation and ulnar clinodactyly of the index fingers but without radiologic signs of hyperphalangy. Furthermore, both individuals have disproportionate short stature, a feature that has not yet been associated with Catel-Manzke syndrome. Our data broaden the phenotypic spectrum of TGDS-associated Catel-Manzke syndrome and expand the indication for diagnostic testing.

Hand Deformities, Congenital/genetics , Hydro-Lyases/genetics , Pierre Robin Syndrome/genetics , Polydactyly/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/physiopathology , Adolescent , Alleles , Child , Child, Preschool , Female , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/physiopathology , Humans , Male , Mutation/genetics , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/physiopathology , Polydactyly/physiopathology
Sleep Breath ; 24(1): 1-5, 2020 Mar.
Article En | MEDLINE | ID: mdl-31240543

There are no standardized management algorithms for neonates with Pierre Robin sequence. Currently available literature is variable in terms of outcomes assessed across studies. In this paper, we have aimed to summarize the currently available literature on longitudinal sleep and respiratory outcomes in Pierre Robin sequence neonates with a focus on identifying gaps in literature and areas for future research development.

Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/therapy , Respiratory Distress Syndrome, Newborn/diagnosis , Sleep Disorders, Intrinsic/diagnosis , Child, Preschool , Follow-Up Studies , Humans , Infant , Infant, Newborn , Longitudinal Studies , Mandibular Osteotomy , Polysomnography , Respiratory Distress Syndrome, Newborn/therapy , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/therapy , Sleep Disorders, Intrinsic/therapy , Tracheostomy , Treatment Outcome
Am J Med Genet A ; 182(3): 437-440, 2020 03.
Article En | MEDLINE | ID: mdl-31833187

Catel-Manzke syndrome is characterized by hand anomalies, Robin sequence, cardiac defects, joint hyperextensibility, and characteristic facial features. Approximately 40 patients with Catel-Manzke have been reported, all with the pathognomonic bilateral or unilateral hyperphalangy caused by an accessory bone between the second metacarpal and proximal phalanx known as Manzke dysostosis. Here we present the first case of molecularly confirmed Catel-Manzke syndrome with Robin sequence but without Manzke dysostosis.

Hand Deformities, Congenital/genetics , Hydro-Lyases/genetics , Mandibulofacial Dysostosis/genetics , Pierre Robin Syndrome/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Adolescent , Child , Child, Preschool , Female , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/pathology , Humans , Mandibulofacial Dysostosis/diagnosis , Mandibulofacial Dysostosis/pathology , Mutation/genetics , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/pathology
Am J Obstet Gynecol ; 221(6): B10-B12, 2019 12.
Article En | MEDLINE | ID: mdl-31787157
J Craniomaxillofac Surg ; 47(11): 1699-1705, 2019 Nov.
Article En | MEDLINE | ID: mdl-31477439

Various treatments, many of them considerably invasive, are currently applied to infants with Robin sequence (RS) and accompanying upper airway obstruction (UAO). We present a narrative review of our data on the Tübingen palatal plate (TPP) which show the following: a) in a randomized trial, the TPP was superior to a sham procedure in alleviating UAO; b) children treated with the TPP in infancy showed an intellectual development within the reference range; c) prone positioning is no alternative, as it is ineffective and associated with an increased risk of sudden death; d) the TPP reduces the mixed-obstructive apnea index to near-normal values, both in isolated and most (83%) syndromic RS, e) of 443 infants (129 syndromic) treated with the TPP in our center, 23 (5%) ultimately received a tracheostomy (all with syndromic RS), f) recent data suggest that the TPP may induce mandibular catch-up growth, g) the TPP may also help to reduce respiratory complications following cleft closure in RS, and h) TPP treatment is applied by various centers around the world, although it is unclear if its effectiveness is invariably controlled by endoscopy and sleep studies, although both are necessary. Given these data from peer-reviewed studies, it may be questioned whether the "First do no harm" principle is always adhered to when subjecting RS infants to more invasive procedures such as mandibular distraction osteogenesis or tongue-lip adhesion.

Airway Obstruction/therapy , Osteogenesis, Distraction , Pierre Robin Syndrome/therapy , Sleep Apnea, Obstructive/therapy , Airway Obstruction/diagnosis , Airway Obstruction/etiology , Child , Humans , Infant , Mandible/growth & development , Mandible/pathology , Pierre Robin Syndrome/complications , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/genetics , Polysomnography , Retrospective Studies , Sleep Apnea, Obstructive/diagnosis , Treatment Outcome
Neuro Endocrinol Lett ; 40(1): 5-9, 2019 Mar.
Article En | MEDLINE | ID: mdl-31184816

Pierre Robin sequence is defined by a triplet of clinical signs in newborns: micrognathia, glossoptosis and tongue-based airway obstruction often accompanied by U-shaped cleft palate. The reported incidence is ranging from 1 to 8.500 to 30.000 newborns. Therapeutic management of Pierre Robin sequence is based on the degree of the airway obstruction. A priori management of such cases can be extremely challenging due to the phenotypic plethora of Pierre Robin Sequence. A ten-day male newborn diagnosed with Pierre Robin was referred to our department for investigation and management of severe airway obstruction. Oxygen support was administered immediately and further examination revealed micrognathia and tongue profusion through the U-shaped cleft palate resulting total obstruction in the rhinopharynx and the nasopharynx resulting in severe dyspnea. Clinical examination and as well further investigation did not reveal further congenital abnormalities. Fiberoptic nasotracheal investigation that confirmed total obstruction of the upper part of respiratory tract was followed by tracheostomy due to signs of persistent respiratory insufficiency. Our report describes the successful algorithm for management of Pierre Robin syndrome as well as highlights the importance of fiberoptic intubation in such rare case.

Airway Obstruction/diagnosis , Pierre Robin Syndrome/diagnosis , Airway Obstruction/surgery , Humans , Infant, Newborn , Male , Pierre Robin Syndrome/surgery , Tracheostomy
Clin Plast Surg ; 46(2): 249-259, 2019 Apr.
Article En | MEDLINE | ID: mdl-30851756

Pierre Robin sequence consists of clinical triad of micrognathia, glossoptosis, and airway compromise with variable inclusion of cleft palate. Evaluation of airway obstruction includes physical examination, polysomnography for obstruction events, and a combination of nasoendoscopy and bronchoscopy to search for synchronous obstructive lesions. A multidisciplinary approach is required given the high rate of syndromic disease. Management of airway obstruction and feeding starts with nonsurgical maneuvers, such as prone and lateral positioning, nasopharyngeal stenting, and continuous positive airway pressure. Surgical management includes mandibular distraction and tongue-lip adhesion. Subglottic obstruction and central sleep apnea may best be treated with tracheostomy.

Airway Obstruction/therapy , Pierre Robin Syndrome/complications , Pierre Robin Syndrome/surgery , Airway Obstruction/diagnosis , Airway Obstruction/etiology , Female , Humans , Infant , Male , Mandible/surgery , Mouth/embryology , Osteogenesis, Distraction , Pierre Robin Syndrome/diagnosis , Polysomnography , Tracheostomy
Rev. bras. oftalmol ; 78(1): 46-48, jan.-fev. 2019. tab, graf
Article Pt | LILACS | ID: biblio-990797

Resumo A síndrome de Pierre Robin (PRS) consiste em uma tríade de anomalias caracterizada por micrognatia, glossoptose e fissura de palato, comumente associada com outras síndromes e ocasionalmente com alterações oculares. Na Síndrome de Duane (DRS), há uma falha na inervação do reto lateral pelo VI nervo, com inervação anômala do reto lateral por fibras do III nervo. Ainda que a PRS já tenha sido associada com mais de 50 outras síndromes, não existe na literatura relato de casos de associação com a DRS familiar. Dessa forma, esse trabalho tem por objetivo relatar um caso dessa associação em um paciente de 29 anos com recorrência das síndromes na família.

Abstract The Pierre Robin Syndrome (PRS) consists of a triad of anomalies characterized by micrognathia, glossoptosis and fissure of the palate, usually associated with other syndromes e occasionally associated with ocular variations. In Duane Retraction Syndrome (DRS), there is a failure in the lateral rectus innervation by the VI cranial nerve, with anomalous innervation of the lateral rectus by fibers of the III nerve. Even though PRS has already been associated with more than 50 other syndromes, there is not any report in literature of association with familial DRS. Thus, this work aims to report a case of this association in a 29 years old patient with recurrence of the syndromes in the family.

Humans , Male , Adult , Abducens Nerve/abnormalities , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/genetics , Eye Diseases, Hereditary/diagnosis , Duane Retraction Syndrome/diagnosis
Otolaryngol Head Neck Surg ; 160(2): 246-254, 2019 02.
Article En | MEDLINE | ID: mdl-30325698

OBJECTIVE: To assess the dental class occlusion and lateral cephalometry of children with conservatively treated Pierre Robin sequence (PRS) and to identify associations between these findings and prepalatoplasty cleft palate measurements. STUDY DESIGN: Retrospective cohort study. SUBJECTS AND METHODS: Among 22 patients with PRS, the following data were prospectively collected: demographics and preoperative cleft palate measurements. After patients reached age 6 years, an orthodontist assessed dental occlusion class and performed a lateral cephalometric analysis. PRS cephalometric data were compared with reference population values. Bivariate logistic regression was used to test the association with malocclusion class. Results are presented as odds ratios with 95% profile likelihood confidence intervals. The association between cleft measurements and cephalometric parameters was tested with Spearman's correlation ( rs). RESULTS: All 22 patients had bimaxillary hypoplasia and were prone to hyperdivergency, with a 41% rate of dental class III malocclusion. An increased anterior growth of the still retrusive mandible mostly accounts for the occurrence of the class III malocclusion in PRS (class II SNB = 74.3° vs class III SNB = 77.6°, P = .04). A larger cleft at the time of the cleft repair (mean, 11 months) was associated with increased mandibular retrusion (smaller SNB angle, rs = -0.5, P = .02). CONCLUSIONS: The 41% rate of class III malocclusion among these conservatively treated patients needs to be considered in the choice of the initial airway approach. The future impact of early mandibular advancement will have to be determined.

Cleft Palate/surgery , Malocclusion, Angle Class III/surgery , Orthognathic Surgical Procedures/methods , Pierre Robin Syndrome/surgery , Cephalometry/methods , Child , Cohort Studies , Confidence Intervals , Female , Hospitals, University , Humans , Logistic Models , Male , Malocclusion, Angle Class III/etiology , Odds Ratio , Pierre Robin Syndrome/complications , Pierre Robin Syndrome/diagnosis , Predictive Value of Tests , Prognosis , Quebec , Retrospective Studies , Risk Assessment , Treatment Outcome
Cleft Palate Craniofac J ; 56(3): 298-306, 2019 03.
Article En | MEDLINE | ID: mdl-29791187

OBJECTIVE: The workup of patients with Pierre Robin sequence (PRS) consists of a physical examination, O2 saturation, and polysomnography to determine the severity of respiratory obstruction and need for surgery. We suggest that capillary blood gas (CBG) may be a better physiologic representation of airway obstruction and should be routinely used in the management of patients with PRS. DESIGN: This is a multicenter study based on a retrospective review of medical records. SETTING: The study was performed at tertiary care centers. INTERVENTIONS: Patients with PRS <1 year old underwent mandibular distraction osteogenesis. MAIN OUTCOME MEASURE: Using successful treatment outcome as a reference standard, receiver operating characteristic (ROC) curve was used to determine the accuracy of the diagnostic test and values for the best sensitivity and specificity to determine the need for surgical intervention. RESULTS: Of 73 patients, 48 had sporadic PRS, 23 had syndromes, 2 had micrognathia, not otherwise specified. Mandibular distraction osteogenesis was performed in 62 patients at a mean age of 39 days. The mean initial Apnea-Hypopnea Index (AHI) in nonsurgical versus surgical groups was 10 versus 31 ( P = .063), pH 7.41 versus 7.34 ( P = .003), pCO2 43 versus 56 ( P < .001), and HCO3 27 versus 30 ( P = .022). The ROC curve showed that pCO2 of 49.5 has the best specificity (100%) and sensitivity (72.6%) profile in terms of need for definitive airway. CONCLUSION: A simple CBG heel stick may better predict the physiologic effects of obstructive apnea; therefore, it should be added to the algorithm of PRS workup.

Pierre Robin Syndrome , Airway Obstruction , Humans , Infant , Mandible , Osteogenesis, Distraction , Pierre Robin Syndrome/diagnosis , Polysomnography , Retrospective Studies , Treatment Outcome
Am J Med Genet A ; 176(12): 2911-2914, 2018 12.
Article En | MEDLINE | ID: mdl-30450804

TARP syndrome (talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava) is a rare X-linked condition. As more patients are identified through genetic testing, it is increasingly clear that the original TARP acronym does not fully describe the complete phenotypic spectrum of this syndrome. The presented patient had genetically confirmed TARP syndrome and demonstrated new findings of hydronephrosis and hemodynamically significant hypertrophic obstructive cardiomyopathy. The patient also had physical findings common with previously reported individuals with TARP syndrome in the literature but not described by the TARP acronym. These features include central nervous system dysfunction, renal abnormalities, cardiac lesions other than atrial septal defect or persistent left superior vena cava, and distal limb defects other than talipes equinovarus. By adding to the known spectrum of the TARP phenotype, this report will aid clinicians as they care for patients with this rare condition.

Clubfoot/diagnosis , Clubfoot/genetics , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/genetics , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/genetics , Cause of Death , Genetic Association Studies , Genetic Predisposition to Disease , Genetic Testing , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Mutation , Phenotype , Prognosis , RNA-Binding Proteins/genetics
Am J Med Genet A ; 176(12): 2915-2918, 2018 12.
Article En | MEDLINE | ID: mdl-30462380

TARP syndrome (talipes equinovarus, atrial septal defect, Robin sequence, and persistence of the left superior vena cava) is a rare X-linked syndrome often resulting in pre- or post-natal lethality in affected males. In 2010, RBM10 was identified as the disease-causing gene, and we describe the first adult patient with TARP syndrome at age 28 years, hereby expanding the phenotypic spectrum. Our patient had Robin sequence, atrial septal defect, intellectual disability, scoliosis, and other findings previously associated with TARP syndrome. In addition, he had a prominent nose and nasal bridge, esotropia, displacement of lacrimal points in the cranial direction, small teeth, and chin dimple, which are the findings that have not previously been associated with TARP syndrome. Our patient was found to carry a hemizygous c.273_283delinsA RBM10 mutation in exon 4, an exon skipped in three of five protein-coding transcripts, suggesting a possible explanation for our patient surviving to adulthood. Direct sequencing of maternal DNA indicated possible mosaicism, which was confirmed by massive parallel sequencing. One of two sisters were heterozygous for the mutation. Therefore, we recommend sisters of patients with TARP syndrome be carrier tested before family planning regardless of carrier testing results of the mother. Based on our patient and previously reported patients, we suggest TARP syndrome be considered as a possible diagnosis in males with severe or profound intellectual disability combined with septal heart defect, and Robin sequence, micrognathia, or cleft palate.

Clubfoot/diagnosis , Clubfoot/genetics , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/genetics , Pierre Robin Syndrome/diagnosis , Pierre Robin Syndrome/genetics , Adult , Clubfoot/therapy , DNA Mutational Analysis , Facies , Genetic Association Studies/methods , Genetic Predisposition to Disease , Heart Defects, Congenital/therapy , Humans , Loss of Function Mutation , Male , Open Reading Frames , Pedigree , Phenotype , Pierre Robin Syndrome/therapy , RNA-Binding Proteins/genetics