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CASE REPORT
Year : 2015  |  Volume : 4  |  Issue : 1  |  Page : 51-53

Acrocallosal syndrome with additional features in a neonate


Department of Neonatology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion (East), Mumbai, Maharashtra, India

Date of Web Publication10-Feb-2015

Correspondence Address:
Deeparaj Ganapati Hegde
Department of Neonatology, LTMMC and Hospital, Sion (East), Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.151171

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  Abstract 

Acrocallosal syndrome (ACLS) is a rare genetic disorder having characteristic craniofacial abnormalities, distinctive limb malformations, and brain anomalies. Though the typical phenotypic features help the clinician to identify this syndrome at birth, few overlapping features with Joubert syndrome and hydrolethalus syndrome, could confuse the clinical picture. In this report, we describe a neonate with ACLS having additional features not described previously. The inheritance and overlapping clinical features with other disorders are also discussed.

Keywords: Acrocallosal syndrome, agenesis of corpus callosum, neonate, postaxial polydactyly


How to cite this article:
Hegde DG, Mondkar J, Manerkar S. Acrocallosal syndrome with additional features in a neonate. J Clin Neonatol 2015;4:51-3

How to cite this URL:
Hegde DG, Mondkar J, Manerkar S. Acrocallosal syndrome with additional features in a neonate. J Clin Neonatol [serial online] 2015 [cited 2020 Sep 30];4:51-3. Available from: http://www.jcnonweb.com/text.asp?2015/4/1/51/151171


  Introduction Top


Acrocallosal syndrome (ACLS) (Online Mendelian Inheritance in Man [OMIM] 200990) is an autosomal recessive disorder characterized by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. [1] The symptoms and physical findings can be quite variable and overlap with other disorders such as Joubert and hydrolethalus syndromes. KIF7 mutations have been now implicated in causing ACLS and have been classified under the category of ciliopathies - a group of disorders in which oligogenic inheritance is frequent. [2],[3] We herein, describe a case of ACLS in a neonate who had additional features not described previously.


  Case report Top


A term female neonate born out of consanguineous marriage at 37 weeks of gestation by normal vaginal delivery was admitted in our neonatal intensive care unit for evaluation of dysmorphic features immediately after birth. Antenatal history was uneventful, and the baby had cried immediately after birth. She weighed 2650 g (50 th percentile) with a head circumference of 36 cm (95 th percentile) and measured 46 cm (between 10 th and 25 th percentile). On examination, she had facial dysmorphism in the form of macrocephaly, wide forehead, epicanthal folds, posteriorly rotated low-set ears, broad nasal bridge, micrognathia and high arched palate [Figure 1]. Alveolar ridges in the mouth and wide-spaced nipples were also noted. Examination of the limbs were remarkable for postaxial polydactyly of hands and hallux duplication in the feet [Figure 1] and [Figure 2].
Figure 1: Photograph showing micrognathia, low-set ears, postaxial polydactyly of the hands, and wide-spaced nipples

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Figure 2: Photograph showing bilateral hallux duplication

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Computed tomography scan-brain revealed agenesis of corpus callosum with colpocephaly of both occipital horns of lateral ventricles. Though a diagnosis of ACLS was made in view of typical anomalies, bilateral microphthalmos, furrowed tongue and redundant skin folds over the nape were noted as additional phenotypic features [Figure 1] and [Figure 3]. A skeletal survey showed 11 pairs of ribs with sixth to eighth ribs on the left side being abnormally oriented, which were unusual findings [Figure 4]. A 4 mm ostium secundum-atrial septal defect was seen in two-dimensional-echo. Ultrasonography of the abdomen revealed bilateral polycystic kidneys, an additional anomaly not reported previously in ACLS. Baby developed seizures on 2 nd day of life and slipped into altered sensorium. She was put on mechanical ventilator for 1 day but expired on the 3 rd postnatal day. Genetic counseling of the parents was done and the autosomal recessive nature of the disorder was explained. Folic acid supplementation to prevent ACLS in further pregnancies was advised as ACLS is a milder variant of anencephaly.
Figure 3: Photograph showing alveolar ridges and furrowed tongue

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Figure 4: Radiograph showing 11 pairs of ribs with some ribs on the left side abnormally oriented. Also note the inferiorly displaced left scapula

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  Discussion Top


We describe a case of ACLS in a neonate who manifested with additional dysmorphic features. Also known as Schinzel ACLS, it is an extremely rare genetically heterogeneous autosomal recessive disorder characterized by agenesis of corpus callosum, hallux duplication, postaxial polydactyly, craniofacial anomalies and in most patients psychomotor retardation. The distinctive developmental anomalies and dysmorphism makes it easy to identify this syndrome at birth as in our case. However, during the last few years, new cases with unusual pre and postnatal phenotypic features are described. [4] The clinical spectrum has been broadened to include severe central nervous system (CNS) abnormalities like anencephaly and cystic malformations of brain. [1],[5]

The diagnosis of ACLS is based on the criteria laid by Courtens et al. (a) Total or partial absence of the corpus callosum on neuroimaging. (b) Minor craniofacial anomalies (prominent forehead, hypertelorism, short nose with anteverted nostrils and large anterior fontanel. (c) Moderate to severe psychomotor retardation (with hypotonia) and (d) polydactyly. The presence of three of the four criteria is suggestive of the diagnosis of ACLS. Our patient had all the four features. [6] Mutations in KIF7 gene located on chromosome 15q26.1, a key component of the sonic hedgehog pathway, as being seen as responsible for this syndrome. Putoux et al. reported that, despite the absence of two major features namely polydactyly/hallux duplication or agenesis of corpus callosum, ACLS could be diagnosed in 4/5 cases by sequencing KIF7 gene. [2] The most consistent findings were prominent forehead, hypertelorism, and CNS abnormalities such as vermis dysgenesis with brain stem anomalies (molar tooth sign).

KIF7 is known to regulate the function of primary cilia, and ACLS is now categorized as a ciliopathy - a group of disorders in which oligogenic inheritance is frequent. [3] It is noteworthy that mutations in KIF7 are also responsible for Joubert syndrome-12 (OMIM 200990), characterized by the hallmark finding of "molar tooth sign" on neuroimaging. This syndrome also has some overlapping phenotypic features with ACLS [Table 1]. [7] This again provides evidence for oligogenic inheritance in ACLS and might probably be responsible for phenotypic variability of KIF7 - related disorders. The index case did not show this classical sign on neuroimaging and hence the diagnosis of Joubert syndrome was ruled out.
Table 1: Overlapping features of acrocallosal syndrome Joubert syndrome and Hydrolethalus syndrome seen in the index case


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Hydrolethalus-2 (OMIM 614120) is an allelic disorder with more severe phenotype and death in utero. [8] It shares few features of ACLS like absent corpus callosum, preaxial polydactyly of feet, and postaxial polydactyly of hands. However, the gestation of most affected patients is complicated by polyhydramnios. Intrauterine growth deficiency is the rule. Most of the cases are still born, and few die within the first few hours. In the index patient, neither was there a history of polyhydramnios, nor was there hydrocephalus which is essential to diagnose hydrolethalus syndrome. [9] However, microphthalmia which was seen in our case, is frequently a described feature of hydrolethalus syndrome.

Our patient had some additional features hitherto not reported in the literature of ACLS. A genetic work up would have been desirable, but unfortunately could not be done due to nonavailability of facilities and short survival period of the index case.

 
  References Top

1.
Koenig R, Bach A, Woelki U, Grzeschik KH, Fuchs S. Spectrum of the acrocallosal syndrome. Am J Med Genet 2002;108:7-11.  Back to cited text no. 1
    
2.
Putoux A, Nampoothiri S, Laurent N, Cormier-Daire V, Beales PL, Schinzel A, et al. Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome. J Med Genet 2012;49:713-20.  Back to cited text no. 2
    
3.
Walsh DM, Shalev SA, Simpson MA, Morgan NV, Gelman-Kohan Z, Chemke J, et al. Acrocallosal syndrome: Identification of a novel KIF7 mutation and evidence for oligogenic inheritance. Eur J Med Genet 2013;56:39-42.  Back to cited text no. 3
    
4.
Gül D, Ulucan H, Unay B, Akin R, Gökçay E. Acrocallosal syndrome: Report of five Turkish patients. Clin Dysmorphol 2004;13:241-6.  Back to cited text no. 4
    
5.
Kedar I, Amiel A, Fejgin M, Drugan A. Recurrent anencephaly as a primary manifestation of the acrocallosal syndrome. Am J Med Genet 1996;62:415-6.  Back to cited text no. 5
    
6.
Courtens W, Vamos E, Christophe C, Schinzel A. Acrocallosal syndrome in an Algerian boy born to consanguineous parents: Review of the literature and further delineation of the syndrome. Am J Med Genet 1997;69:17-22.  Back to cited text no. 6
    
7.
Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, et al. Mutations in KIF7 link joubert syndrome with sonic hedgehog signaling and microtubule dynamics. J Clin Invest 2011;121:2662-7.  Back to cited text no. 7
    
8.
Putoux A, Thomas S, Coene KL, Davis EE, Alanay Y, Ogur G, et al. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet 2011;43:601-6.  Back to cited text no. 8
    
9.
Jones KL. Hydrolethalus Syndrome. In: Smith's Recognizable Patterns of Human Malformation. 6 th ed. Philadelphia: Elsevier Saunders; 2006. p. 204-5.  Back to cited text no. 9
    


    Figures

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

  [Table 1]



 

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