Hypertelorism, and Arthrogryposis multiplex congenita

Intermediate nemaline myopathy is a type of nemaline myopathy (NM; see this term) that shows features of typical NM (see this term) in neonates with a more severe progression.

• Hypertelorism
• Low-set ears
• Flexion contracture
• Motor delay
• Skeletal muscle atrophy

SOURCES: ORPHANET MENDELIAN

Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with cholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

MYASTHENIC SYNDROME, CONGENITAL, 11, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS11 Is also known as cms1e, formerly|myasthenic syndrome, congenital, ie, formerly|cms ie, formerly

• Generalized hypotonia
• Hypertelorism
• Micrognathia
• Muscle weakness
• Ptosis

SOURCES: MESH OMIM MENDELIAN

Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.

LETHAL CONGENITAL CONTRACTURE SYNDROME TYPE 1 Is also known as herva disease|multiple contracture syndrome, finnish type|lccs|lccs1

• Short stature
• Hypertelorism
• Micrognathia
• Flexion contracture
• Skeletal muscle atrophy

SOURCES: MESH OMIM ORPHANET MENDELIAN

Autosomal recessive primary microcephaly-17 (MCPH17) is a severe neurologic disorder characterized by very small head circumference that is apparent at birth and worsens over time (up to -12 SD). Affected individuals have delayed psychomotor development, intellectual disability, spasticity, axial hypotonia, and dysmorphic features. Brain imaging shows a simplified gyral pattern; more severe cases have lissencephaly with hypoplasia of the brainstem and cerebellum (summary by Harding et al., 2016).For a phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (OMIM ).

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

• Scoliosis
• Growth delay
• Hypertelorism
• Micrognathia
• Abnormal facial shape

SOURCES: OMIM MENDELIAN

• Intellectual disability
• Seizures
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN

Pontocerebellar hypoplasia type 1D is a severe autosomal recessive neurologic disorder characterized by severe hypotonia and a motor neuronopathy apparent at birth or in infancy. Patients have respiratory insufficiency, feeding difficulties, and severely delayed or minimal gross motor development. Other features may include eye movement abnormalities, poor overall growth, contractures. Brain imaging shows progressive cerebellar atrophy with relative sparing of the brainstem (summary by Burns et al., 2018).For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (OMIM ).

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

SOURCES: OMIM MENDELIAN

EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY Is also known as myopathy, early-onset, with fatal cardiomyopathy|salih myopathy|eomfc

• Generalized hypotonia
• Scoliosis
• Hypertelorism
• Muscle weakness
• Ptosis

SOURCES: MESH ORPHANET OMIM MENDELIAN

Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first months or years of life (summary by Knierim et al., 2016). Genetic Heterogeneity of Spinal Muscular Atrophy With Congenital Bone FracturesSee also SMABF2 (OMIM ), caused by mutation in the ASCC1 gene (OMIM ) on chromosome 10q22.

• Global developmental delay
• Generalized hypotonia
• Hypertelorism
• Muscle weakness
• Flexion contracture

SOURCES: OMIM MENDELIAN

1q21.1 microduplication syndrome is a rare partial autosomal trisomy/tetrasomy with incomplete penetrance and variable expression characterized by macrocephaly, developmental delay, intellectual disability, psychiatric disturbances (autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, mood disorders) and mild facial dysmorphism (high forehead, hypertelorism). Other associated features include congenital heart defects, hypotonia, short stature, scoliosis.

1Q21.1 MICRODUPLICATION SYNDROME Is also known as trisomy 1q21.1|dup(1)(q21.1)

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MESH MENDELIAN