Generalized hypotonia, and Agenesis of corpus callosum

Combined oxidative phosphorylation defect type 21 is a rare mitochondrial disease characterized by axial hypotonia with limb hypertonia, developmental delay, hyperlactatemia, central nervous system anomalies visible on magnetic resonance imaging (e.g. corpus callosum hypoplasia, lesions of the globus pallidus) and multiple deficiency of the mitochondrial respiratory chain complexes in muscle tissue, but not in fibroblasts or liver.

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 21 Is also known as coxpd21

• Global developmental delay
• Generalized hypotonia
• Hypoplasia of the corpus callosum
• Hypertonia
• Muscular hypotonia of the trunk

SOURCES: ORPHANET OMIM MENDELIAN

Pyruvate dehydrogenase E1-beta deficiency is an extremely rare form of pyruvate dehydrogenase deficiency (PDHD, see this term) characterized by severe lactic acidosis, developmental delay and hypotonia.

PYRUVATE DEHYDROGENASE E1-BETA DEFICIENCY Is also known as pdhbd|pyruvate dehydrogenase complex e1 component subunit beta deficiency

• Generalized hypotonia
• Agenesis of corpus callosum
• Acidosis
• Lactic acidosis
• Metabolic acidosis

SOURCES: OMIM ORPHANET MESH MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Spasticity

SOURCES: MESH OMIM MENDELIAN

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Scoliosis
• Hyperreflexia

SOURCES: OMIM MENDELIAN

Polymicrogyria with optic nerve hypoplasia is a rare genetic syndrome with central nervous system malformations characterized by severe developmental delay, neonatal hypotonia, seizures, optic nerve hypoplasia and distinct central nervous system malformations including extensive bilateral polymicrogyria, dysplastic or absent corpus callosum and malformed brainstem with loss of demarcation of the pontomedullary junction.

POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA Is also known as polymicrogyria with optic nerve hypoplasia

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Hyporeflexia

SOURCES: OMIM MESH ORPHANET MENDELIAN

Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness.Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see {236100}).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET OMIM MENDELIAN

Complex cortical dysplasia with other brain malformations-7 is an autosomal dominant, clinically heterogeneous disorder showing a wide spectrum of abnormalities of cortical brain development. The most severely affected patients are fetuses with microlissencephaly, absence of the cortical plate, agenesis of the corpus callosum, and severely hypoplastic brainstem and cerebellum. Other patients have lissencephaly, polymicrogyria, cortical dysplasia, or neuronal heterotopia. Those with less severe malformations can survive, but usually have some degree of neurologic impairment, such as mental retardation, seizures, and movement abnormalities (summary by Chang et al., 2006; Fallet-Bianco et al., 2014).For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (OMIM ).

POLYMICROGYRIA DUE TO TUBB2B MUTATION Is also known as polymicrogyria, symmetric or asymmetric|pmgysa

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM ORPHANET MENDELIAN

Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-6 is a bicoronal form associated with bony defects in the sagittal, metopic, or lambdoid sutures (Twigg et al., 2015).For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Scoliosis

SOURCES: OMIM MENDELIAN

Arnold-Chiari malformation type II is a rare, central nervous system malformation characterized by caudal displacement of the cerebellum, pons, medulla and fourth ventricle through the foramen magnum into the spinal canal, and is typically associated with myelomeningocele. Variable other central nervous system abnormalities might be present (partial or complete agenesis of the corpus callosum, a small fourth ventricle, obstructive hydrocephalus, falx and tentorium defects, and polygyria). Symptoms include hypotonia, apnea with cyanosis, dysphagia, opisthotonus, nystagmus, spasticity, ataxia, and occipital headache.

ARNOLD-CHIARI MALFORMATION TYPE II Is also known as cm2|arnold-chiari malformation|chiari malformation type ii|chiari malformation type 2|arnold-chiari malformation type 2

• Generalized hypotonia
• Ataxia
• Nystagmus
• Muscular hypotonia
• Spasticity

SOURCES: OMIM ORPHANET MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET MESH OMIM MENDELIAN