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Autosomal Recessive Microcephaly with Severe Psychomotor Retardation By 1. E. Schefferl, M. Baraitser2,j. Wilson l, c. GOdfrey3 and E. M. Brettl IDepartment of Neurology, 2Department of Clinieal Geneties, The Hospital for Siek Children, Great Ormond Street, London, U.K., and 3Department of General Paediatries, North Middlesex Hospital, Edmonton, London, U.K.
Autosomal recessive microcephaly has long been recognized in association with normal early motor development and mild to severe mental retardation. We report three sibling pairs with microcephaly and severe neurological impairment. These cases and other sibling pairs reported in the literature illustrate that microcephaly with spasticity and severe mental retardation mayaIso have autosomal recessive inheritance. Furthermore this severely affected group of patients forms a significant proportion of cases of genetic microcephaly. We looked for specific morphological features to identify these forms of genetic microcephaly for genetic counselling, but failed to find characteristic abnormalities among our group of patients.
Case reports
Case 1 These identical male twins (Fig. 1) were born at 37 weeks gestation to unrelated Indian parents. There was a normal 8-year-old daughter. The pregnancy was complicated by a moderate bleed at 2 months gestation. Twin 1 weighed 2.61 kg at birth with a head circumference of 33 cm, and twin 2 weighed 1.96 kg with a head circumference of 33.5 cm. There were no neonatal problems. Concern was raised when microcephaly was recognised at 6 months.
Keywords Autosomal recessive Psychomotor retardation, severe
microcephaly
Introduction Microcephaly is defined as a head circumference which is beyond 3 standard deviations below the mean for age and sex. Genetically determined autosomal recessive microcephaly is a diagnosis of exclusion after thorough investigation for an underlying cause such as prenatal exposure to an infectious or chemical agent, irradiation, chromosomal abnormalities, metabolic causes, structural malformations of the brain and birth trauma. The classical picture of "microcephalia vera" is associated with relatively normal early motor milestones and mild to severe mental retardation. The incidence of genetic microcephaly has been quoted as ranging from 1:25,000-1:50,000 (1) to 1:250,000 (12) live births. Recurrence risks have been considered small when microcephaly is associated with severe neurological problems and investigations
Received November 20, 1990; aeeepted January 8, 1991 Neuropediatries 23 (1992) 53-56 © Hippokrates Verlag Stuttgart
Fig. 1
Twins described in Case 1.
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Abstract
have not shown an aetiology. We report 3 sibling pairs with microcephaly and severe neurological problems to emphasize that genetic microcephaly may differ from the classical picture of microcephaly "vera", and we advocate caution in genetic counselling in the former group.
Neuropediatrics 23 (1992)
By 9 months, the development of the twins was obviously delayed. Neither child could roll over, sit up or reach for an object. They had cooed at 5 to 6 months and laughed, but were not babbling. They had impaired hearing on formal testing. Their head circumferences had fallen from the 10th centile at birth to 5 standard deviations below the mean (5 SD < M) by 9 months 39 cm. On examination at 9 months, each twin was ahle to follow a light through 180 degrees and had an alternating convergent squint. Both had generalised hypertonia and hyperreflexia with poor head contro!. They showed persistence of primitive reflexes with a partial M oro response and retained bilateral palmar grasp reflexes. There were no dysmorphic features. The twins were monozygous on blood zygosity testing. Skull x-rays and congenital infection screens were unremarkahle. CT head scans on both children showed an asymmetrie skull vault with generalised dilatation of the ventricular system and prominent cerebral and cerebellar sulci.
1. E. Scheffer et al
her parents were concerned as she was not socially responsive when called, followed only briefly, and was not grasping or sitting. On examination at 6 months her weight was 6 kg (3rd centile), length 71.5 cm (above 90th centile) and head circumference 39.5 cm (2.3 SD
Autosomal Recessive Microcephaly with Severe Psychomotor Retardation By 1. E. Schefferl, M. Baraitser2,j. Wilson l, c. GOdfrey3 and E. M. Brettl IDepartment of Neurology, 2Department of Clinieal Geneties, The Hospital for Siek Children, Great Ormond Street, London, U.K., and 3Department of General Paediatries, North Middlesex Hospital, Edmonton, London, U.K.
Autosomal recessive microcephaly has long been recognized in association with normal early motor development and mild to severe mental retardation. We report three sibling pairs with microcephaly and severe neurological impairment. These cases and other sibling pairs reported in the literature illustrate that microcephaly with spasticity and severe mental retardation mayaIso have autosomal recessive inheritance. Furthermore this severely affected group of patients forms a significant proportion of cases of genetic microcephaly. We looked for specific morphological features to identify these forms of genetic microcephaly for genetic counselling, but failed to find characteristic abnormalities among our group of patients.
Case reports
Case 1 These identical male twins (Fig. 1) were born at 37 weeks gestation to unrelated Indian parents. There was a normal 8-year-old daughter. The pregnancy was complicated by a moderate bleed at 2 months gestation. Twin 1 weighed 2.61 kg at birth with a head circumference of 33 cm, and twin 2 weighed 1.96 kg with a head circumference of 33.5 cm. There were no neonatal problems. Concern was raised when microcephaly was recognised at 6 months.
Keywords Autosomal recessive Psychomotor retardation, severe
microcephaly
Introduction Microcephaly is defined as a head circumference which is beyond 3 standard deviations below the mean for age and sex. Genetically determined autosomal recessive microcephaly is a diagnosis of exclusion after thorough investigation for an underlying cause such as prenatal exposure to an infectious or chemical agent, irradiation, chromosomal abnormalities, metabolic causes, structural malformations of the brain and birth trauma. The classical picture of "microcephalia vera" is associated with relatively normal early motor milestones and mild to severe mental retardation. The incidence of genetic microcephaly has been quoted as ranging from 1:25,000-1:50,000 (1) to 1:250,000 (12) live births. Recurrence risks have been considered small when microcephaly is associated with severe neurological problems and investigations
Received November 20, 1990; aeeepted January 8, 1991 Neuropediatries 23 (1992) 53-56 © Hippokrates Verlag Stuttgart
Fig. 1
Twins described in Case 1.
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Abstract
have not shown an aetiology. We report 3 sibling pairs with microcephaly and severe neurological problems to emphasize that genetic microcephaly may differ from the classical picture of microcephaly "vera", and we advocate caution in genetic counselling in the former group.
Neuropediatrics 23 (1992)
By 9 months, the development of the twins was obviously delayed. Neither child could roll over, sit up or reach for an object. They had cooed at 5 to 6 months and laughed, but were not babbling. They had impaired hearing on formal testing. Their head circumferences had fallen from the 10th centile at birth to 5 standard deviations below the mean (5 SD < M) by 9 months 39 cm. On examination at 9 months, each twin was ahle to follow a light through 180 degrees and had an alternating convergent squint. Both had generalised hypertonia and hyperreflexia with poor head contro!. They showed persistence of primitive reflexes with a partial M oro response and retained bilateral palmar grasp reflexes. There were no dysmorphic features. The twins were monozygous on blood zygosity testing. Skull x-rays and congenital infection screens were unremarkahle. CT head scans on both children showed an asymmetrie skull vault with generalised dilatation of the ventricular system and prominent cerebral and cerebellar sulci.
1. E. Scheffer et al
her parents were concerned as she was not socially responsive when called, followed only briefly, and was not grasping or sitting. On examination at 6 months her weight was 6 kg (3rd centile), length 71.5 cm (above 90th centile) and head circumference 39.5 cm (2.3 SD
