Glossary in Congenital Malformations

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Syndromes and SequencesHead

#Jacobsen syndrome (deletion 11q syndrome):

·         Genetics: There is deletion of chromosome 11q23 to qter in most cases and the region related to the clinical phenotype appears to be located on 11q24.1. Three quarter of the patients are female. Deletion of 11q may arise de novo or from inheriting a derived chromosome from a parent carrying a balanced translocation.

·    Clinical features: Intrauterine growth retardtion and failure to thrive are the early symtoms. There is almost always moderate to severe mental retardation. Except those that die of their cardiac defect, they are compatible with long-term survival. Hypotonia in infancy frequently progress toward spasticity. There are also joint contractures and cardiac defects. Myelodysplastic changes have also been reported. The severity of clinical manifestation may be correlated with the amount of deleted chromosome [Ono J et al., Clin Genet 1996 Dec;50(6):474-8 ]

·         Characteristic cranial facial features: Trigonencephaly and microcephaly are frequently seen. Typical facial features include “carp mouth”, high arched palate, borad and/or flat nasal bridge, micrognathia, hypertelorism, and epicanthal folds.

·         CNS findings:

·    Malformations: There is no known asscoiated pattern of involvement. Abnormalities that have been described include holoprosencephaly, pachygyria [Lin JH et al., Am J Med Genet 1998 Feb 3;75(4):341-4 ]

·         White matter changes: Abnormality of supratentorial white matter and also been reported and include diffuse hyperintensity of cerebral white matter with multiple high internsity areas in deep-subcortical white matter on T2-weighted images. These findings sugges either delay of myelination, degeneration of myelin, or vasogenic infarctions. However, since the clinical conditions of these two patients do not decline, the abnormal imaging finding may represent delayed myelination rather than demyelination [Ono J et al., 1994].

·         Ocular features: Abnormal ophthalmic findings are an integral part of Jacobsen syndrome and feature include retinal dysplasia, optic atrophy, retinal reduplication and ocular coloboma.

#Joubert Syndrome: Pathologically show multiple malformations of the cerebellum and brain stem.

·         Genetics: Autosomal recessive. An X-linked variant may exist.

·         Clinical features include episodic hyperpnea, abnormal eye movements (nystagmus), ataxia, mental retardation, and polydyctyly. Respiratory abnormalities are prominent during neonatal period but may be absent in up to half of the cases. Antenatal diagnosis is impossible because the syndrome is defined clinically. Ataxia and mental retardation become manifest in late infancy and childhood, at a time when respiratory abnormalities decrease and become undetectable. Joubert syndrome is usually fatal.

·         Pathology: Usually associated with agenesis or hypoplasia of the cerebellar vermis with associated enlargement of the cisterna magna. The superior cerebellar peduncles are almost at right angles to the brain stem (horozontal superior peduncle). Typical umbrella shaped 4th ventricles may be seen on imaging. Additional neuropathologic lesions include dysplastic and segmented dentate nucleus, heterotopias of cortical cerebellar cells and nuclei, several anomnalies of brain stem nuclei such as C-shaped dysplasia of the inferior olivary nucleus, and absence of decussation of the pyramidal tracts. Ocular abnormalies include choroidoretinal coloboma and retinal abnormalies. Renal abnormalities may also be associated.

NeuroLearn NeuroHelp Malformations General Syndromes For Comment: KarMing-Fung@ouhsc.edu