Generalized hypotonia, and Hyporeflexia

MTDPS12A is characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies (summary by Thompson et al., 2016).For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (OMIM ).

• Seizures
• Generalized hypotonia
• Muscle weakness
• Respiratory insufficiency
• Cardiomyopathy

SOURCES: OMIM MENDELIAN

Spinocerebellar ataxia type 14 (SCA14) is a rare mild subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by slowly progressive ataxia, dysarthria and nystagmus.

SPINOCEREBELLAR ATAXIA TYPE 14 Is also known as sca14

• Generalized hypotonia
• Cognitive impairment
• Dysarthria
• Tremor
• Myoclonus

SOURCES: ORPHANET MENDELIAN

Autosomal recessive mental retardation-53 is a neurodevelopmental disorder characterized by severely delayed psychomotor development, hypotonia apparent since infancy, and early-onset seizures in most patients. Some patients may have additional features, such as cerebellar hypoplasia and ataxia. MRT53 is one of a group of similar neurologic disorders resulting from biochemical defects in the glycosylphosphatidylinositol (GPI) biosynthetic pathway (summary by Makrythanasis et al., 2016).For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (OMIM ).

MENTAL RETARDATION, AUTOSOMAL RECESSIVE 53; MRT53 Is also known as glycosylphosphatidylinositol biosynthesis defect 13|gpibd13

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

SOURCES: OMIM MENDELIAN

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is an inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome (GBS; see this term).

ACUTE INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY Is also known as guillain-barrÉ syndrome, acute inflammatory demyelinating polyradiculoneuropathic form|aidp|acute inflammatory polyneuropathy|acute idiopathic demyelinating polyneuropathy|gbs, acute inflammatory demyelinating polyradiculoneuropathic form

• Generalized hypotonia
• Hyporeflexia
• Gait ataxia
• Unsteady gait
• Drooling

SOURCES: ORPHANET MENDELIAN

Spinocerebellar ataxia type 31 (SCA31) is a very rare subtype of autosomal dominant cerebellar ataxia type III (ADCA type III; see this term) characterized by the late-onset of cerebral ataxia, dysarthria and horizontal gaze nystagmus, and that is occasionally accompanied by pyramidal signs, tremor, decreased vibration sense and hearing difficulties.

SPINOCEREBELLAR ATAXIA TYPE 31 Is also known as sca31|spinocerebellar ataxia, 16q22-linked

• Generalized hypotonia
• Hearing impairment
• Ataxia
• Nystagmus
• Sensorineural hearing impairment

SOURCES: MESH OMIM ORPHANET MENDELIAN

Combined oxidative phosphorylation defect type 13 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by normal early development followed by the sudden onset in infancy of poor feeding, dysphagia, truncal (followed by global) hypotonia, motor regression, abnormal movements (i.e. severe dystonia of limbs, choreoathetosis, facial dyskinesias) and reduced tendon reflexes. The disease course is severe but nonprogressive.

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 13 Is also known as coxpd13

• Generalized hypotonia
• Growth delay
• Muscle weakness
• Feeding difficulties
• Skeletal muscle atrophy

SOURCES: ORPHANET OMIM MENDELIAN

Reducing-body myopathy (RBM) is a rare myopathy characterized pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase (MAG) in the absence of substrate, alpha-glycerophosphate. The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium (NBT) in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. The clinical features of RBM are variable; a severe form has onset in infancy or early childhood and results in severe disability or early death, and a less severe form has onset in late childhood or adulthood (RBMX1B ) (summary by Liewluck et al., 2007 and Shalaby et al., 2009).

• Generalized hypotonia
• Scoliosis
• Muscle weakness
• Flexion contracture
• Motor delay

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

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare neurometabolic disorder of gamma-aminobutyric acid (GABA) metabolism with a nonspecific clinical presentation (ranging from mild to severe) with the most frequent symptoms being cognitive impairment with prominent deficit in expressive language, hypotonia, ataxia, epilepsy, and behavioral dysregulation.

SUCCINIC SEMIALDEHYDE DEHYDROGENASE DEFICIENCY Is also known as ssadh deficiency|4-hydroxybutyric aciduria|gaba metabolic defect|gamma-hydroxybutyric aciduria

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

SOURCES: OMIM MESH ORPHANET MENDELIAN

Scapulohumeroperoneal myopathy is an autosomal dominant muscle disorder characterized by slowly progressive muscle weakness and atrophy affecting both proximal and distal muscles of the upper and lower limbs. Onset is usually in the first decade and can be as early as infancy, although some patients do not notice symptoms until young adulthood. There is marked variability in severity (summary by Zukosky et al., 2015).

• Generalized hypotonia
• Scoliosis
• Muscle weakness
• Gait disturbance
• Myopathy

SOURCES: OMIM ORPHANET MENDELIAN