Multiple Congenital Anomalies Syndrome With Cloverleaf Skull

Sharony et al. (2002) described 3 sibs (2 females, 1 male), born of Arabic-Muslim consanguineous healthy parents, with an apparently 'new' lethal familial short-limb bone dysplasia associated with multiple congenital anomalies (MCA). Clinical abnormalities included short limbs and short hands, cloverleaf skull, frontal bossing, wide anterior fontanel, hypertelorism, bilateral microphthalmia, cataract, low-set ears, narrow chest, ambiguous genitalia, cardiac ventricular septal defect, and agenesis of the corpus callosum. Radiologic abnormalities included cloverleaf skull, hypoplastic clavicles and scapulas, thin and wavy cupped ribs, flat vertebral bodies with coronal clefting and several unossified vertebral pedicles, and hypoossification of the pubic bone. Long bones were short and bowed with abnormal metaphyses and unossified epiphyses. Degenerating chondrocytes with disorganization of the hypertrophied cartilage and short disorganized columns of hypertrophied areas were found. Sharony et al. (2002) postulated an autosomal recessive mode of inheritance.