Lethal X-linked microcephaly with dysmorphic features, bilateral optic pathway aplasia and normal eyes
V A Fabian1, J Nelson, N M Smith
1Department of Neuropathology, Royal Perth Hospital, Western Australia.
Abstract:
We describe a family, consisting of two brothers and a maternal uncle who died of an apparently identical condition, within a few days of birth, suggestive of an X-linked mode of inheritance. The propositus (the older sibling) was investigated in detail and showed the following clinical features: microcephaly, facial dysmorphism, malformations of hands and feet, and cryptorchidism. Examination of the brain revealed arhinencephaly, a primitive gyral pattern, arrested cortical maturation, absence of corticofugal tracts and corpus callosum, agenesis of the optic pathway with preserved eyes and oculomotor system, absent auditory pathway, agenesis of the pars compacta of the substantia nigra and severe hypoplasia of the cerebellum and its connections. This family belongs to the group of X-linked microcephalies and has some features in common with the Juberg-Marsidi syndrome. The fact that the CNS abnormalities were incompatible with life and the facial dysmorphic features were quite different makes it unlikely that the affected individuals in this family had Juberg-Marsidi syndrome. However, this does not exclude the possibility that more restricted anterior induction defects may occur in some X-linked microcephalies such as Juberg-Marsidi syndrome resulting in prolonged survival.
Insights
This study details a rare X-linked microcephaly syndrome in a family, characterized by severe brain malformations and distinct facial features, leading to early death. The condition differs from Juberg-Marsidi syndrome, highlighting genetic diversity in X-linked microcephalies.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- X-linked microcephaly represents a group of genetic disorders affecting brain development.
- Understanding these conditions is crucial for diagnosing and managing affected families.
Observation:
- A family presented with two brothers and a maternal uncle dying neonatally from an identical condition.
- The propositus exhibited microcephaly, facial dysmorphism, limb malformations, and cryptorchidism.
- Detailed examination revealed severe central nervous system (CNS) abnormalities including arhinencephaly, cortical dysplasia, and agenesis of major pathways.
Findings:
- The observed CNS malformations were incompatible with life.
- The distinct facial dysmorphism and severe brain abnormalities differentiate this condition from Juberg-Marsidi syndrome.
- The pattern suggests a novel X-linked microcephaly syndrome.
Implications:
- This case expands the spectrum of known X-linked microcephaly disorders.
- It underscores the genetic heterogeneity within this group of developmental brain defects.
- Further research may elucidate specific genes and pathways involved in these severe neurodevelopmental disorders.
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