Cardiomyopathy, and Ptosis

Low match EMERY-DREIFUSS MUSCULAR DYSTROPHY 5, AUTOSOMAL DOMINANT; EDMD5

• Muscle weakness
• Ptosis
• Respiratory insufficiency
• Cardiomyopathy
• Congestive heart failure

SOURCES: OMIM MENDELIAN

Low match MYASTHENIC SYNDROME, CONGENITAL, 12; CMS12

Congenital myasthenic syndrome-12 is an autosomal recessive neuromuscular disorder characterized by onset of proximal muscle weakness in the first decade. EMG classically shows a decremental response to repeated nerve stimulation. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors (summary by Senderek et al., 2011).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

MYASTHENIC SYNDROME, CONGENITAL, 12; CMS12 Is also known as myasthenic syndrome, congenital, with tubular aggregates 1|cmsta1

• Muscle weakness
• Ptosis
• Motor delay
• Cardiomyopathy
• Myopathy

SOURCES: OMIM MENDELIAN

Low match MITOCHONDRIAL DNA DEPLETION SYNDROME 12B (CARDIOMYOPATHIC TYPE), AUTOSOMAL RECESSIVE; MTDPS12B

Mitochondrial DNA depletion syndrome-12B is an autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance, and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged-red fibers, mtDNA depletion, and accumulation of abnormal mitochondria (summary by Echaniz-Laguna et al., 2012).For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (OMIM ).

• Muscle weakness
• Cataract
• Ptosis
• Cognitive impairment
• Skeletal muscle atrophy

SOURCES: OMIM MENDELIAN

Low match NOONAN SYNDROME 5; NS5

• Intellectual disability
• Global developmental delay
• Short stature
• Hypertelorism
• Abnormal facial shape

SOURCES: MESH OMIM MENDELIAN

Low match AGEL AMYLOIDOSIS

AGel amyloidosis is a rare, systemic amyloidosis characterized by a triad of ophthalmologic, neurologic and dermatologic findings due to the deposition of gelsolin amyloid fibrils in these tissues. Clinical manifestations include corneal lattice dystrophy, cranial neuropathy, especially affecting the facial nerve, bulbar signs, cutis laxa, increased skin fragility, and less commonly peripheral neuropathy and renal failure.

AGEL AMYLOIDOSIS Is also known as amyloid cranial neuropathy with lattice corneal dystrophy|amyloidosis, meretoja type|amyloidosis due to mutant gelsolin|amyloidosis v|familial amyloidosis, finnish type|gelsolin amyloidosis|familial amyloid polyneuropathy type iv|hereditary amyloidosis, f

• Cataract
• Ptosis
• Peripheral neuropathy
• Cardiomyopathy
• Renal insufficiency

SOURCES: ORPHANET OMIM MESH MENDELIAN

Low match NEUROFIBROMATOSIS-NOONAN SYNDROME

Neurofibromatosis-Noonan syndrome (NFNS) is a RASopathy and a variant of neurofibromatosis type 1 (NF1) characterized by the combination of features of NF1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas, and Noonan syndrome (NS), such as short stature, typical facial features (hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly rotated ears with a thickened helix, and a broad forehead), congenital heart defects and unusual pectus deformity. As these three entities have significant phenotypic overlap, molecular genetic testing is often necessary for a correct diagnosis (such as when café-au-lait spots are present in patients diagnosed with NS).

NEUROFIBROMATOSIS-NOONAN SYNDROME Is also known as nfns|neurofibromatosis type 1-noonan syndrome

• Short stature
• Hypertelorism
• Cryptorchidism
• Ptosis
• Downslanted palpebral fissures

SOURCES: ORPHANET MENDELIAN

Low match PROXIMAL MYOPATHY WITH EXTRAPYRAMIDAL SIGNS

Proximal myopathy with extrapyramidal signs is a rare, hereditary non-dystrophic myopathy characterized by proximal muscle weakness, delayed motor development, learning difficulties, and progressive extrapyramidal motor signs including chorea, dystonia and tremor. Variable additional features have been reported - ataxia, microcephaly, ophthalmoplegia, ptosis, and optic atrophy.

• Global developmental delay
• Hearing impairment
• Microcephaly
• Ataxia
• Muscle weakness

SOURCES: ORPHANET OMIM MENDELIAN

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 33; COXPD33

COXPD33 is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. The phenotype is highly variable, ranging from death in infancy to adult-onset progressive external ophthalmoplegia (PEO) and myopathy. A common finding is cardiomyopathy and increased serum lactate (summary by Feichtinger et al., 2017).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

• Muscle weakness
• Ptosis
• Peripheral neuropathy
• Hepatomegaly
• Fatigue

SOURCES: OMIM MENDELIAN

Low match CARDIOFACIOCUTANEOUS SYNDROME 2; CFC2

Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects, and mental retardation (summary by Niihori et al., 2006). In a phenotypic comparison of BRAF (OMIM )-positive and KRAS-positive individuals with CFC, Niihori et al. (2006) observed that patients with KRAS mutations did not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma, that were present in patients with BRAF mutation.

• Intellectual disability
• Global developmental delay
• Short stature
• Hypertelorism
• Ptosis

SOURCES: OMIM MENDELIAN

Low match POLYGLUCOSAN BODY MYOPATHY 1 WITH OR WITHOUT IMMUNODEFICIENCY; PGBM1

Polyglucosan body myopathy-1 is an autosomal recessive disorder characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood (summary by Boisson et al., 2012 and Nilsson et al., 2013). Genetic Heterogeneity of Polyglucosan Body MyopathySee also PGBM2 (OMIM ), caused by mutation in the GYG1 gene (OMIM ) on chromosome 3q24.

POLYGLUCOSAN BODY MYOPATHY 1 WITH OR WITHOUT IMMUNODEFICIENCY; PGBM1 Is also known as polyglucosan body myopathy, early-onset, with or without immunodeficiency|pbmei

• Scoliosis
• Growth delay
• Failure to thrive
• Muscle weakness
• Ptosis

SOURCES: OMIM MENDELIAN