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Primary acalvaria an orphan disease: Case report and review of literature

1 Department of Pediatrics, LLRM Medical College, Meerut, Uttar Pradesh, India
2 Department of Pediatric Cardiology, LLRM Medical College, Meerut, Uttar Pradesh, India
3 Department of Radiology, LLRM Medical College, Meerut, Uttar Pradesh, India

Date of Submission13-Jun-2021
Date of Decision20-Nov-2021
Date of Acceptance14-Nov-2021
Date of Web Publication30-Jan-2023

Correspondence Address:
Munesh Tomar,
Department of Pediatric Cardiology, LLRM Medical College, Garh Road, Jai Bhim Nagar, Meerut 250002, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_134_21



Acalvaria is a very rare congenital anomaly; thus, it is considered to be an orphan disease and is characterized by complete or partial absence of flat calvaria bones, lax skull, dura mater, and associated muscles. In this report, we describe a case of female neonate with primary acalvaria finding on neuroimaging associated with cleft palate.

Keywords: Acalvaria, orphan disease, skull reconstruction

How to cite this URL:
Faizan R, Tomar M, Usmani Y. Primary acalvaria an orphan disease: Case report and review of literature. J Pediatr Neurosci [Epub ahead of print] [cited 2023 Dec 5]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=368796

   Case Report Top

A just-born female baby, product of natural conception with nonconsanguineous marriage, born to a 28-year-old mother via preterm vaginal delivery at 34 weeks of gestation. The baby is fourth in birth order. First two siblings are healthy, whereas third sibling was born as extremely preterm (24 weeks gestation) and could not survive. Mother was an unbooked case without any antenatal follow-up. With the onset of premature labor, she was referred from a nearby primary health center to the tertiary health care facility. Although the ambulance was on its way to medical college, baby got delivered. On receiving, baby’s heart rate was 158/min and respiratory rate was 68/min with subcostal and intercostal retractions. Baby weight was 1340 g and length was 40 cm, with a head circumference of 28 cm (<10 centiles). On general examination, there was no facial dysmorphism; upper limbs were normal but in lower limb saddle gap was seen between first and second toes. In oral cavity, complete cleft palate was seen. Neonatal reflexes and tone in all four limbs were normal for gestational age. There was no evidence of spinal dysmorphism. Head was very soft on palpation giving feeling of soft bogginess swelling over the scalp but was covered by healthy skin and hair [Figure 1]. Neuroimaging (cranial ultrasonography, noncontrast computerized tomography [CT] and magnetic resonance imaging [MRI]) was done for detailed evaluation. CT head revealed increased echogenic brain parenchyma, hypoplasia of body of corpus callosum, diffuse cerebral edema, and partial absence of frontal, occipital, and bilateral parietal bone [[Figure 2]A and B]. On MRI brain, there was hypoplasia of posterior body and splenium of corpus callosum, and hypoplasia of muscles of scalp [[Figure 2]C].
Figure 1: Photograph of baby showing healthy skin and hair over head

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Figure 2: (A) CT head with three-dimensional reconstruction showing bilateral partial frontal, parietal, and occipital absence. (B) CT head coronal section showing partial temporal and parietal bones. (C) MRI sagittal view showing hypoplasia of posterior body and splenium of corpus callosum along with hypoplasia of scalp muscles (frontalis and occipitalis)

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As part of anomaly scan, ultrasound abdomen and echocardiography were also done in which no other associated anomaly was detected.

In the neonatal intensive care unit (NICU), baby was managed by continuous positive airway pressure (CPAP) (at 40% FiO2 at 5 cm of water), intravenous fluid, empirical antibiotics, and maintenance of temperature. Gradually respiratory distress was settled and baby was shifted from CPAP to nasal prongs and further oxygen was weaned off. Simultaneously orogastric feed was initiated. Neurosurgical opinion was taken and was advised for medical follow-up. Baby was discharged on 12th day of life on orogastric feed with advice of close follow-up.

Karyotype was in the plan but the family did not give consent for same.

   Discussion Top

Term acalvaria and acrania are often used interchangeably but we prefer to use acalvaria because acrania is defined as complete absence of entire cranium including skull base.[1],[2] In our present case, there was partial absence of calvaria bones and scalp muscles hypoplasia with normal skull base. Acalvaria can be primary or secondary. Primary acalvaria is defined as complete or partial absence of calvaria bones, dura mater, scalp muscles with normal base of skull, and complete intracranial contents, whereas secondary acalvaria is defined as acalvaria associated with amniotic band syndrome, neural tube defect, or use of angiotensinogen-converting enzyme inhibitor during pregnancy.[2],[3] Our case fits into primary. Reported literature showed rarity of entity with an incidence of 1:1,00,000 with very few case reports[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] [Table 1]. This disorder is found to be heterogeneous without any genetic predilection with some female predominance.[5] The etiopathogenesis is unclear but it is considered due to post neurulation defect during embryological development, which implies that it may be due to impaired migration of mesenchyme (responsible for formation of muscles and bones) leading to covering of brain only with skin.[5]
Table 1: Reported cases of acalvaria

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By imaging, the acalvaria can be diagnosed as early as 12th weeks of gestation by transvaginal ultrasonography (TVS USG) and three-dimensional (3D) image reconstruction with ultrasonography. Although nonspecific, high alpha-fetoprotein (AFP) levels may help to support the diagnosis.[5],[6] In our case, the mother did not have any antenatal screening and so diagnosis could be made after birth only.

Acalvaria has been found to be associated with multiple anomalies such as holoprosencephaly, micro polygyria, facial clefts, cardiac anomalies such as atrial septal defect (ASD), transposition of great arteries (TGA), club foot, omphalocele, and amniotic band syndrome, hence making the thorough examination necessary to determine prognosis and predict the final outcome.[6],[7] Some differential diagnosis for acalvaria includes severe osteogenesis imperfecta, congenital hypophosphatemia, and anencephaly. The most common differential diagnosis is considered to be anencephaly. The acalvaria is differentiated from anencephaly by the presence of a normal cerebral hemisphere[5] [Table 2]. Currently, the initial management of acalvaria is mainly conservative, which aims at supportive care and management of associated anomalies if present. Acalvaria is very rare and fatal anomaly with only a few reported living cases. The spontaneous growth of bone has been observed in a few cases of scalp defect, for example, cutis aplasia, which has increased the importance of conservative management of acalvaria patient. These patients can further go for skull reconstruction by cranioplasty and bone grafting.[5] 3D printing is now used in medicine in various fields and there are reports of use of this technique in skull reconstruction in cases of skull trauma in adult patients.[8] Calvaria reconstruction was done by locating the cranial defect margin on a skull surface image generated from a 3D head CT scan. A right-to-left mirrored image of an average 3D skull surface template image was then fitted to the patient’s skull surface image. The area around the defect was cut out and stitched to the previously isolated defect margin. This defect-filling surface was then tapered and printed out in 3D. The 3D print implant model is then recasted in a biocompatible material.[8],[9] In future, this technique of 3D printing might be used for skull reconstruction in children with acalvaria. The presence of dura or its graft such as abdominal fascia or cerafix (Dura Substitute is a synthetic, porous polymer matrix composed of spun poly(lactic-co-glycolic acid) and poly-p-dioxanone) or surgicel (is a resorbable oxidized cellulose material in a sterile fabric meshwork) is must for retention of cerebrospinal fluid (CSF) in cranium. Probably the 3D-printed calvaria substitute would be used over dura or synthetic graft.
Table 2: Salient features of differential diagnosis of acalvaria

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The surgical correction of the skull defect has been recently reported in a child with partial acalvaria in which the operators used the present bone as a graft to cover the defect, giving a temporal but stable coverture.[12]

Our patient was managed conservatively in NICU and after detailed counseling and consultation with a neurosurgeon, the patient was discharged on the 12th day of life on orogastric feeding. Parents were trained for orogastric feeding. Baby is now 1-month-old and is being kept on close medical follow-up.

   Conclusion Top

Acalvaria is an extremely rare fatal anomaly. Very few cases are reported and to date documented management is nonsurgical. Use of 3D printing and calvaria reconstruction in patients with posttraumatic calvaria loss gives hope of surgical management of acalvaria.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients 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.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Kwon TH, King J, Jeanty P. Acrania: Review of 13 cases. Fetus 1919;1:1-4.  Back to cited text no. 1
Rios LTM, Martins MG, Simões VMF, Nunes MV, Marques PF, Godoy SHCS. Primary acalvaria: A case report. Radiol Bras 2010;43:273-4.  Back to cited text no. 2
Ri S, Shin J, Je B, Choi BM, Hypocalvaria of newborn infant: Intrauterine exposure to an angiotensin receptor blocker. Perinatology2017;28:103-7.  Back to cited text no. 3
Ouma JR. Acalvaria: Report of a case and discussion of the literature. Br J Neurosurg 2019;33:224-5.  Back to cited text no. 4
Gupta V, Kumar S. Acalvaria: A rare congenital malformation. J Pediatr Neurosci 2012;7:185-7.  Back to cited text no. 5
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Harris CP, Townsend JJ, Carey JC. Acalvaria: A unique congenital anomaly. Am J Med Genet 1993;46:694-9.  Back to cited text no. 10
Evans C, Marton T, Rutter S, Anumba DO, Whitby EH, Cohen MC. Cranial vault defects: The description of three cases that illustrate a spectrum of anomalies. Pediatr Dev Pathol 2009;12:96-102.  Back to cited text no. 11
Caycedo DJ, Castillo-Huila JP, Zapata-Copete JA, Santacruz LF. Novel surgical approach to acalvaria. J Craniofac Surg 2021;32:210-1.  Back to cited text no. 12
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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