Microcephaly-chorioretinopathy syndrome, autosomal recessive form. A case report

ABSTRACT CONTEXT: The autosomal recessive form of microcephaly-chorioretinopathy syndrome is a rare genetic condition that is considered to be an important differential diagnosis with congenital toxoplasmosis. CASE REPORT: Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis. However, his serological tests for congenital infections, including toxoplasmosis, were negative. He was the first child of young, healthy and consanguineous parents (fourth-degree relatives). The parents had normal head circumferences and intelligence. The patient presented microcephaly and specific abnormalities of the retina, with multiple diffuse oval areas of pigmentation and patches of chorioretinal atrophy associated with diffuse pigmentation of the fundus. Ophthalmological evaluations on the parents were normal. A computed tomography scan of the child’s head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications. We did not find any lymphedema in his hands and feet. He had postnatal growth retardation, severe mental retardation and cerebral palsy. CONCLUSIONS: The finding of chorioretinal lesions in a child with microcephaly should raise suspicions of the autosomal recessive form of microcephaly-chorioretinopathy syndrome, especially in cases with an atypical pattern of eye fundus and consanguinity. A specific diagnosis is essential for an appropriate clinical evaluation and for genetic counseling for the patients and their families.


INTRODUCTION
The findings of microcephaly and chorioretinopathy in a newborn usually lead to the hypothesis of congenital infection, especially in countries where some of these diseases, like toxoplasmosis, are prevalent. 1[4] The aim of our report was to describe a boy who presented microcephaly-chorioretinopathy syndrome that was compatible with an autosomal recessive form.This is a rare condition that is considered to be an important differential diagnosis with congenital toxoplasmosis.

CASE REPORT
Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis.He was the first child of young, healthy and consanguineous parents (fourth-degree relatives), and had a healthy sister of three years of age (Figure 1).
The mother had a history of one previous loss of pregnancy.She said that she had not smoked, consumed alcohol or made use of illicit drugs during the pregnancy.The family history was negative for similar cases.The parents had normal head circumferences and intelligence.The child was born from an uneventful pregnancy, by means of cesarean delivery, at eight months of gestational age, weighing 2,740 g (i.e.within the range of the 50-90 th percentiles), measuring 47 cm (50-98 th percentiles), with head circumference of 32 cm (10-50 th percentiles) and Apgar score of 9 at five minutes.Serological tests for congenital infections (toxoplasmosis, rubella, cytomegalovirus, herpes simplex and syphilis) were negative.No lymphedema was observed in his hands and feet and the patient also did not present anemia, petechiae, maculopapular rash or jaundice.
He was hospitalized due to pneumonia on four occasions, the first at four months of age.At four years and seven months, his weight was 11 kg (< 3 rd percentile), length 101 cm (< 3 rd percentile), head circumference 42 cm (< 2 nd percentile) and ear length 6.5 cm (> 97 th percentile).He had a high arched palate, prominent large ears, pointed chin, spasticity and atrophy of the upper and lower limbs, right-side cryptorchid testis and bilateral overlapping of the second and fourth toes over the third toes (Figure 2).In the neurological evaluation, he was hypertonic, presented little social interaction and had significant neuropsychomotor delay.He was not capable of supporting his head or speaking words, but he did not have seizures.A computed tomography scan of the head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications.Electroencephalographic evaluation showed a cerebral pattern with little organization and subcortical paroxysms.
In an eye examination, he did not fix on or follow objects and he was unable to perform the Snellen visual acuity test.
He did not have any relative afferent pupillary defect, ocular misalignment or abnormalities in the slit-lamp examination.
Significant blepharitis was observed in both eyes.His pupils were isochoric and, in an eye fundus examination, peripapillary retinal atrophy was observed.There was abnormality of the peripheral retinal pigment epithelium, typical of chorioretinopathy, with poorly defined borders and little perilesional pigmentation, along with a minor juxtapapillary lesion occupying the macula and multiple clumps of pigment spread across the retina (Figure 3).Ophthalmological assessments on his parents and sister were normal.
The radiological investigation showed microcephaly and bilateral hip dislocation.High resolution GTG-banded karyotyping was normal (46,XY).He developed chickenpox and died as a result of complications at 11 years of age, and no electroretinography could be performed at that time.No autopsy was performed.In our review of the literature, using the descriptors "Microcephaly" AND "Chorioretinopathy" AND "(Autosomal Recessive)", we found only two related articles (one case report and one original article) (Table 1). 4,8Th e case report was made by Cantú et al. 4 Th e authors described two sisters and their brother who presented microcephaly, microphthalmia, chorioretinal degeneration and optic atrophy.Similar to our patient, they also had delayed growth and development. 4Consanguinity, a feature seen in our family, was also suspected by Cantú

Figure 1 .
Figure 1.Pedigree of the family showing the consanguinity observed between the patient's parents.
microcephaly and specifi c abnormalities of the retina with multiple diff use oval areas of pigmentation and patches of chorioretinal atrophy associated with diff use pigmentation of the fundus, and a family history of consanguinity between the parents.Th e ophthalmological evaluations on these fi rst-degree relatives were normal.Our patient, similar to those described by Schmidt et al. 3 and Abdel-Salam et al., 5 also presented postnatal growth retardation, severe mental retardation and cerebral palsy.Th ese fi ndings are consistent with the autosomal recessive form of microcephaly-chorioretinopathy syndrome (OMIM #251270).6Lymphedema, a feature not seen in our patient, has also been described only in association with families presenting dominant inheritance.7

Figure 3 .
Figure 3. Images of the eye fundus examination showing peripapillary retinal atrophy; abnormality of the peripheral retinal pigment epithelium, typical of chorioretinopathy, with poorly defi ned borders and little perilesional pigmentation; and a minor juxtapapillary lesion occupying the macula and multiple clumps of pigment spread across the retina in the right eye (RE: right eye; LE: left eye).

Figure 2 .
Figure 2. Appearance of the patient at fi ve years of age showing microcephaly, prominent large ears, pointed chin (A and B), and spasticity of upper limbs (A).A B