Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Users Online: 235
 
About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Advertise Login 
     


 
 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 214-217

Otopalatodigital dysplasia type II: Uncommon skeletal disorder seen in Calabar, Nigeria


1 Department of Paediatrics, Faculty of Medicine, University of Calabar, Calabar, Nigeria
2 Department of Paediatrics, University of Calabar Teaching Hospital, Calabar, Nigeria
3 Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Calabar, Calabar, Nigeria
4 Department of Histopathology, University of Calabar, Calabar, Nigeria

Date of Submission10-Oct-2019
Date of Decision23-Mar-2020
Date of Acceptance30-Mar-2020
Date of Web Publication07-Aug-2020

Correspondence Address:
Dr. Sunday Oteikwu Ochigbo
Department of Paediatrics, Faculty of Medicine, University of Calabar, Calabar
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_110_19

Rights and Permissions
  Abstract 


Otopalatodigital (OPD) dysplasia type 2 is an X-linked rare congenital disorder causing severe skeletal and extraskeletal manifestations. This results from the gain of function mutations in the filamin A (FLNA) gene which is protein actin responsible for modulation and reorganization of the actin cytoskeleton. The baby's mother had polyhydramnios, delivered at 39 weeks, with low Apgar scores and weight 1.5 kg. Examination revealed aplasia of the humerus, ulnar, fibula, hypoplasia of the digits, hanging malformed thumb, thoracolumbar lordosis, short thoracic vertebra, and incomplete ribs with brittle bones. Extraskeletal anomalies were cleft lip and palate, hydrocephalus, and omphalocele. The diagnosis of OPD type 2 with intra-uterine growth retardation and severe birth asphyxia was made, the baby died 7 min after birth. The autopsy confirmed highlighted findings without abnormalities of the lungs, trachea, kidneys, and heart. We report this case to highlight the fact that the presence of polyhydramnios should raise a high index of suspicion for further diagnostic evaluation to exclude the otopalatoskeletal syndrome.

Keywords: Baby, brittle, omphalocele, phallus


How to cite this article:
Ochigbo SO, Adams EB, Akpan UB, Edem UD. Otopalatodigital dysplasia type II: Uncommon skeletal disorder seen in Calabar, Nigeria. J Clin Neonatol 2020;9:214-7

How to cite this URL:
Ochigbo SO, Adams EB, Akpan UB, Edem UD. Otopalatodigital dysplasia type II: Uncommon skeletal disorder seen in Calabar, Nigeria. J Clin Neonatol [serial online] 2020 [cited 2020 Dec 4];9:214-7. Available from: https://www.jcnonweb.com/text.asp?2020/9/3/214/291639




  Introduction Top


Otopalatodigital (OPD) dysplasia type 2 (OMIM 304120) is a genetic disorder characterized by craniofacial, skeletal, visceral, brain, auditory and palatal defects. OPD syndrome disorders include five phenotypical subtypes: OPD type 1, OPD type 2 (OPD2), frontometaphyseal dysplasia, Melnick–Needles syndrome (MNS), and terminal osseous dysplasia with pigmentary defects.[1],[2] The extraskeletal anomalies include hydrocephalus, hearing loss, craniofacial dysmorphism, cerebellar hypoplasia, obstructive uropathy, cardiac defects, and omphalocele.[1] OPD spectrum disorders are X-linked, caused by the gain of function mutations in the FLNA gene which is protein actin responsible for the modulation and reorganization of the actin cytoskeleton.[3] The severity of the presentation is severe in males with perinatal and early neonatal deaths, whereas females present with milder symptoms.[1] Prenatal diagnosis of male fetuses with omphalocele and multiple malformations involving the bones, palate, heart, brain, urinary tracts, and digits should raise the suspicion of this condition. Treatment for OPD is symptomatic and multidisciplinary.


  Case Report Top


A 37-year-old gravida 4 para 3 homemaker was delivered of 1.5 kg baby by elective cesearian section at gestational age of 39 weeks. Apgar scores at birth were 1 and 2 at 1 minute and 5 minutes respectively. The couple is married and nonconsanguineous from the lower socioeconomic class, with three other children without congenital malformations. Mother had neither exposure to any drug, mutagenic agent, nor had a rash during the first trimester. She is not a known hypertensive or diabetics and never had any medical illness. Both parents were physically normal and no history of congenital malformations in any member of both families as shown by the 3 generation pedigree [Figure 1]. The antenatal period was essentially uneventful apart from the ultrasound scan done 2 weeks before delivery which revealed polyhydramnios with some skeletal malformations.
Figure 1: Patients three generation pedigree

Click here to view


Immediately after the delivery, the baby was noticed to be gasping. The baby was small for gestational age, had dysmorphic features with multiple congenital malformations: cleft lip and palate, short neck, absence of nasal septum, and nipples, low-set ears, hypoplastic jaw beaked nose, sutural diastasis, hydrocephalus, umbilical defect (omphalocele), and rudimentary phallus without testicles. The baby had severe generalized skeletal malformations, which included absent humerus, ulnar, fibula, hypoplasia of the digits, hanging malformed thumb, thoracolumbar lordosis, short thoracic vertebra, and incomplete ribs with brittle bones. Talipes calcaneovarus with fanning of the lower digits [Figure 1], [Figure 2], [Figure 3], [Figure 4]. A diagnosis of OPD type 2 with intra-uterine growth retardation (IUGR) and severe birth asphyxia was made. Immediate resuscitation of the baby was instituted but the baby died 7 minutes after birth. The autopsy done confirmed the above findings without abnormalities of the lungs, trachea, kidneys, and heart.
Figure 2: Annotation of affected structures

Click here to view
Figure 3: (a) and (b) Facial dysmorphism and skeletal abnormalities of the limbs

Click here to view
Figure 4: Only the tibia (absence of fibula)

Click here to view



  Discussion Top


This is the first reported case of OPD dysplasia presenting at our center. There was difficulty classifying this index patient because of some cross-cutting features observed. However, the severe skeletal abnormalities, obvious cleft lip and palate, hydrocephalus, and omphalocele made the authors classify this condition as OPD type 2. The association of omphalocele with OPD 2 in a male infant was first described by Stillman et al.[4] The males present with a severe clinical manifestation due to X-linked inheritance, whereas the female carriers usually manifest a subclinical bony dysplasia and facial dysmorphism.[1] Our patient had micropenis with the absence of distinctive scrotum, testis, but the accompanying severe skeletal abnormality could suggest X-linked dominant inheritance, hence, the likelihood of being a genetic male.

The condition was not classified as OPD 1 because of its milder symptoms, hydrocephalus, and omphalocele, which are uncommonly seen in OPD 1. Although omphalocele is a common component of MNS, this condition characteristically does not present with cleft abnormalities which were quite obvious in our patient; however, the presence polyhydramnios and omphalocele may strongly suggest the OPD type 2 as earlier reported by Young et al.[5]

Several reports have shown an increased prevalence of central nervous system, and gastrointestinal tract congenital malformations associated with severe polyhydramnios but severe skeletal abnormalities as seen in the index patient are uncommon.[6],[7] The most affected males die during the perinatal or infancy usually from thoracic hypoplasia resulting in pulmonary insufficiency, and survivors suffer neurodevelopmental delay.[8] Unfortunately, our patient did not live beyond 7 minutes, which may be probably due to the severity of the condition which further strengthened our diagnosis and the gender.[1],[2]

The autopsy report revealed normal lungs, kidneys, and heart which are an unlikely cause of death, however, death could have resulted from placenta insufficiency and possible brain stem injury not unrelated to the IUGR with hydrocephalus.

The absence of fibula on both legs signifies a significant skeletal abnormality which is in keeping with OPD 2. A small or absent fibula and presence of only four toes were reported in a family by Kozlowski et al. as OPD 2, although our patient had four left fingers with the absence of fibula which is in keeping with their findings.[9] Although several associations with OPD 2 have been described, recently, Murphy-Ryan et al. described the presence of bifid tongue, corneal clouding, and Dandy-Walker malformation in a male infant with OPD2.[10] Melnick-Needles Syndrome (MNS), a close differential, was excluded because of the absence of cleft lip/palate and hydrocephalus in MNS.


  Conclusions Top


OPD 2 is a rare condition with multiple severe skeletal manifestations. This has not been reported previously in the region or at our center. The presence of polyhydramnios during the antenatal period should raise a high index of suspicion for further diagnostic evaluation to exclude the otopalatoskeletal syndrome-like OPD 2.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient's parent gave their consent for the images and other clinical information to be reported in the journal. The patient's parent understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We acknowledge the parents of this child who gave consent for autopsy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Verloes A, Lesenfants S, Barr M, Grange DK, Journel H, Lombet J, et al. Fronto-otopalatodigital osteodysplasia: Clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. Am J Med Genet 2000;90:407-22.  Back to cited text no. 1
    
2.
Robertson SP. Otopalatodigital syndrome spectrum disorders: Otopalatodigital syndrome types 1 and 2, frontometaphyseal dysplasia and Melnick-Needles syndrome. Eur J Hum Genet 2007;15:3-9.  Back to cited text no. 2
    
3.
Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, et al. Localized mutations in the gene encoding the cytoskeletal protein filamin a cause diverse malformations in humans. Nat Genet 2003;33:487-91.  Back to cited text no. 3
    
4.
Stillman SC, Davis JG, Meryash DL. Otopalatodigital syndrome 1 and omphaloceles. Dysmorph Clin Genet 1991;5:2-10.  Back to cited text no. 4
    
5.
Young K, Barth CK, Moore C, Weaver DD. Otopalatodigital syndrome type II associated with omphalocele: Report of three cases. Am J Med Genet 1993;45:481-7.  Back to cited text no. 5
    
6.
Kornacki J, Adamczyk M, Wirstlein P, Osinski M, Wender-Ozegowska E. Polyhydramnios-Frequency of congenital anomalies in relation to the value of the amniotic fluid index. Ginekol Pol 2017;88:442-5.  Back to cited text no. 6
    
7.
Lalchan S, Sharma P, Gurung SD. Prevalence of congenital anomalies in polyhydramnios: A hospital-based study from western Nepal. Nepal J Radiol 2018;8:25-9.  Back to cited text no. 7
    
8.
Robertson S, Adam MP, Ardinger HH, Pagon RA, Wallace, SE, Bean LJ, et al. editors. GeneReviews®. Seattle: University of Washington; 1993-2019. [Updated on 2 May 2013; 30 November 2005].  Back to cited text no. 8
    
9.
Kozlowski K, Donovan T, Masel J, Wright RG. Microcephalic, osteodysplastic, primordial dwarfism. Australas Radiol 1993;37:111-4.  Back to cited text no. 9
    
10.
Murphy-Ryan M, Babovic-Vuksanovic D, Lindor N. Bifid tongue, Corneal clouding, and Dandy-walker malformation in a male infant with Otopalatodigital syndrome type 2.. Am J Med Genet Part A 2011;155:855-9.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

Top
 
 
  Search
 
Similar in PUBMED
  Search Pubmed for
  Search in Google Scholar for
Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusions
References
Article Figures

 Article Access Statistics
    Viewed154    
    Printed15    
    Emailed0    
    PDF Downloaded37    
    Comments [Add]    

Recommend this journal