Callosal agenesis in craniofrontonasal dysplasia

Clinical History

An 8-year-old female patient from Pakistan, with thick, wiry hair, came to our attention for facial asymmetry, ocular hypertelorism, and mental retardation.

Imaging Findings

Skull X-rays (Fig. 1) showed disproportion between the vault and the base and diastasis of the facial bones. These findings have been confirmed by CT scan (Fig. 2a) which showed malformation of craniofacial complex with global hypoplasia of the facial bones, orbital hypertelorism and frontal bossing. The anterior cranial fossa was shorter but larger than normal, with hypoplasia of the ethmoidal air cells (Fig. 2b). MRI demonstrated several intracranial anomalies (Fig. 3): callosal agenesis, Probst bundle fibres, enlargement of the occipital horns of the lateral ventricles. T1-W images (Fig. 4) showed a focal hyperintensity in the median eminence not attentuated in FAT-SAT sequences, suggesting an ectopic neurohypophysis. The posterior fossa was smaller than normal with displaced cerebellar tonsils.

Discussion

A cranial or craniofacial dysmorphism clinically recognized in infancy could be a consequence of the premature fusion of one or more cranial sutures (craniosynostosis) [1]. A rare condition in the category of craniosynostosis is Craniofrontonasal dysplasia (CFND) first described by Cohen in a female child with coronal synostosis, orbital hypertelorism, broadened nasal root, digital anomalies, longitudinally groved nails and wiry hair. [2] Patients with CFND show many of the same clinical features as those with Frontonasal dysplasia (FND) but imaging findings document a coronal synostosis [3]. Premature closure of a suture retards growth perpendicular to the affected suture but permits parallel growth. Thus the coronal synostosis may account for the clinically observed brachicephaly and frontal bossing. Acrocephaly and dolichocephaly have also been noted [2].
Inheritance plays a significant role in CFND. The EFNB1 gene, encoding ephrin-B1, maps at Xq13.1. Ephrin-B1 plays a guiding role in neural crest cell migration and its mutations cause defects in craniofacial morphogenesis [4]. CFND exhibits an unusual pattern of X-linked inheritance, with a paradoxically greater severity in heterozygous females than in hemizygous males, likely for a random X-inactivation in females. The diagnostic certainty of CFND is established after the presence of a mutation in EFNB1 gene but physical manifestations can guide in the right direction as well as the radiological findings [5]. Radiographic findings have been described as primary (indistinctness of the pathological suture; presence of bony spur along the suture) or secondary (craniofacial deformities as a direct consequence of suture synostosis). Nowadays plain X-ray films have been replaced by CT with three-dimensional reconstruction (3DCT) and maximum intensity projection (MIP) which optimally evaluates the presence and degree of sutural involvement (partial or complete disappearance of the suture, sclerosis along the inner and outer tables) and assesses the associated facial and intracranial abnormalities [5].
In patients who shows neurological impairment and in those with syndromic craniosynostosis, there is the need for an integrated approach based on an association of 3DCT and MRI to evaluate the associated intracranial anomalies like callosal agenesis.
The neuroimaging work-up is of utmost importance in surgical planning and in monitoring the reconstructive results [3].
There is no standard treatment for people with CFND due to a large heterogeneity regarding phenotypic expression. Each patient needs to be assessed and treated (surgical corrections of craniosynostosis, orbital hypertelorism, nasal deformity) based on their specific presentation, in order to restore the aesthetic and functional balance [6].

Differential Diagnosis List

Final Diagnosis

The diagnosis is CFND based on radiological and clinical findings

URL:	https://www.eurorad.org/case/10568
DOI:	10.1594/EURORAD/CASE.10568
ISSN:	1563-4086