Clinical Profile:

A 15 month old baby boy born out of non consanguineous marriage was brought by parents with complaints of abnormal appearance of the head and facial features since birth.

Birth history: Full term forceps vaginal delivery with a birth weight of 3.5kg. The baby did not cry immediately after birth.

History of NICU stay for 19 days.

There is delay in developmental milestones.

For projectile nonbilious vomiting, he had been investigated elsewhere and diagnosed as hydrocephalus due to aqueductal stenosis.

A VP shunt had been done when the boy was 10 months of age.

On examination, the baby was found to have prominent orbits with exophthalmos, macrocephaly, cleft palate, depressed nasal bridge, frontal bossing, asymmetrical skull growth, hypertelorism, low-set ears and hypoplastic maxilla with relative mandibular prognathism (Fig. 1).

Frontal and lateral radiographs of the skull (Fig. 2) show beaten copper appearance indicating remodeling of the brain due to increased intracranial pressure due to fused sutures.

There siu elevation of the superolateral corners of the orbits on both sides giving “harlequin eye deformity”.

The biparietal diameter is wider than the anteroposterior diameter of the skull.

The above features are suggestive of brachycephaly due to coronal suture synostosis.

A VP shunt is seen.

Fig. 3

Axial sections of CT brain (Fig. 3) show increased biparietal diameter of the cranial vault with relatively decreased anteroposterior diameter suggestive of brachycephaly. Asymmetrical regions of thinning and thickening is seen in the calvarial bones. Brain parenchyma is normal.

3D reconstruction of CT images (Fig. 4) show complete fusion of the coronal sutures with brachycephaly. Open anterior fontanelle is seen. Maxilla is hypoplastic.Multiple lacunar defects are seen within the bony calvaria of varying sizes on both sides s/o craniosynostosis with lacunar skull.

Radiological Diagnosis:

The clinical and imaging observations were consistent with Crouzon syndrome with associated corpus callosal agenesis.

The diagnosis of Crouzon syndrome was further confirmed on genomic DNA, using Sanger sequencing, which showed heterozygous mutation in Exon 8 of Fibroblast Growth Factor Receptor 2 gene (FGFR 2), located on Chromosome 10.

Treatment:

A parasagittal craniotomy had been done at the previous treatment center. At our institution, a VP shunt was done. The baby is doing well and is on regular follow up.

Discussion:

Crouzon syndrome is the most common syndrome among the craniosynostosis group. It accounts for about 4.8% of all of them. It commonly has autosomal dominant inheritance with complete penetrance and variable expressivity from subtle to severe forms and characterized by craniosynostosis, exophthalmos, and hypoplastic maxilla with relative mandibular prognathism. The male to female preponderance is 3:1.[1,2]

The skull growth is arrested in perpendicular direction to the fused suture and compensatory overexpansion takes place in the parallel direction to the fused suture.

With the advent of molecular technology, the gene for Crouzon's syndrome could be localized to the fibroblast growth factor receptor II gene (FGFR 2) at the chromosomal locus 10q 25.3-q26, and more than 30 different mutations within the gene have been documented in separate families.

Differential diagnosis of Crouzon's syndrome includes Apert's syndrome, Carpenter syndrome, Pfeiffer syndrome, Saethre-Chotzen syndrome and Jackson Weiss syndrome. Patients with associated acanthosis nigricans can have FGFR3 mutation.[2]

The appearance of an infant with Crouzon's syndrome can vary in severity from a mild presentation with subtle midface deficiency to severe forms with fusion of multiple cranial sutures and marked midface and eye problems.

Upper airway obstruction can lead to acute respiratory distress.Mental retardation is rare in these children.[3,5]

Increased intracranial pressure leading to optic atrophy may occur, which can produce blindness if the condition is not treated.

Management of Crouzon's disease is multidisciplinary and early diagnosis is important. In the first year of life, it is preferred to release the synostotic sutures of the skull to allow adequate cranial volume thus allowing for brain growth and expansion.

Skull reshaping may need to be repeated as the child grows to give the best possible results.[4,5] If necessary, mid-facial advancement and jaw surgery can be done to provide adequate orbital volume and reduce the exophthalmoses to correct the occlusion to an appropriate functional position and to provide for a more normal appearance. Prognosis depends on severity of malformation.[4,5]

References:

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2. Gorlin RJ, Cohen MM, Levin LS. 3rd ed. Oxford: Oxford University Press; 1990. Syndromes of the head and neck; pp. 516–26. [Google Scholar]

3. Crouzon LE. Dysostose cranio-faciale héréditaire. Bulletin de la Société des Médecins des Hôpitaux de Paris. 1912;33:545–55. [Google Scholar].

4. Cohen MM., Jr Craniosynostosis update 1987. Am J Med Genet Suppl. 1988;4:99–148. [PubMed] [Google Scholar].

5. Jarund M, Lauritzen C. Craniofacial dysostosis: Airway obstruction and craniofacial surgery. Scand J Plast Reconstr Surg Hand Surg. 1996;30:275–9. [PubMed] [Google Scholar]