The microcephaly-capillary malformation syndrome

Abstract

We report on three children from two families with a new pattern recognition malformation syndrome consisting of severe congenital microcephaly (MIC), intractable epilepsy including infantile spasms, and generalized capillary malformations that was first reported recently in this journal [Carter et al. (2011); Am J Med Genet A 155: 301-306]. Two of our reported patients are an affected brother and sister, suggesting this is an autosomal recessive severe congenital MIC syndrome.

FIG. 1

Images of Patient 1 (LR#07-155a1), (A–C) at 2.5 years of age, Patient 2 (LR#07-155a2) (D–F) at 9 months of age, and Patient 3 (LR10-168) at birth (G) and 2 months of age (H, I). Note severe microcephaly, bitemporal narrowing with a low-sloping forehead. Images (C, F, I) demonstrate generalized capillary malformations.

FIG. 2

Images of the feet of Patient 1 (LR07-155a1), (A, B) at 3.5 years of age, and Patient 2 (LR07-155a2), (C, D) at 1 year 8 months. Note the short toes and hypoplastic toe nails, with complete nail aplasia of the right first toe and marked overlapping of the left 3rd–4th toes in Patient 1 (A, B).

FIG. 3

EEG of patient 3 (LR10-168) at 7 months of age, showing high voltage (up to 200 µV) and multifocal sharp waves consistent with hypsarrhythmia. A generalized electrodecrement was associated with clinical spasms (marked).

FIG. 4

T1-weighted mid-sagittal and coronal and T2-weighted axial images of a normal patient (A–C) and Patient 1 (LR#07-155a1, D-F), T1-weighted mid-sagittal and T2-weighted axial and coronal images of Patient 2 (LR07-155a2, G–I), T1-weighted mid-sagittal and coronal and T2-weighted axial images of Patient 3 (LR10-168, J–M). Note obvious microcephaly, low-sloping forehead, with diffusely reduced number of gyri, shallow wide sulci consistent with microcephaly with simplified gyri, as well as moderately enlarged extra-axial space and thin cortex in all affected patients.

FIG. 5

Skin biopsy images of Patient 3 (LR10-168). Routine hematoxylin and eosin stained slides at 100× and 400× magnification show a punch biopsy of skin with an unremarkable epidermis and reticular dermis. The capillaries in the papillary dermis are increased in number and are dilated as compared to normal. These biopsy findings are diagnostic of capillary malformations.