Global developmental delay, and Generalized muscle weakness

X-linked myopathy with excessive autophagy is a childhood-onset X-linked myopathy characterised by slow progression of muscle weakness and unique histopathological findings.

X-LINKED MYOPATHY WITH EXCESSIVE AUTOPHAGY Is also known as xmea|vacuolar myopathy

• Global developmental delay
• Generalized hypotonia
• Muscle weakness
• Cardiomyopathy
• Myopathy

SOURCES: OMIM ORPHANET MENDELIAN

The 2 dominantly inherited, clinically similar types of episodic flaccid generalized weakness, HOKPP and HYPP, are distinguished by the changes in serum potassium levels during paralytic attacks. An important clinical difference between the 2 entities is represented by the triggers of attacks of weakness, e.g., HYPP can be provoked by oral potassium administration, whereas this is a remedy for HOKPP. Concurrence of myotonia is found in HYPP but usually not in HOKPP patients (Jurkat-Rott et al., 2000).Jurkatt-Rott and Lehmann-Horn (2007) provided a review of the clinical features, pathogenesis, and therapeutic options for HYPP.

HYPERKALEMIC PERIODIC PARALYSIS; HYPP Is also known as adynamia episodica hereditaria with or without myotonia|gamstorp disease

• Global developmental delay
• Short stature
• Microcephaly
• Muscle weakness
• Abnormal facial shape

SOURCES: OMIM MENDELIAN

PARAMYOTONIA CONGENITA OF VON EULENBURG; PMC Is also known as paralysis periodica paramyotonica

• Global developmental delay
• Generalized hypotonia
• Muscle weakness
• Abnormal facial shape
• Pain

SOURCES: OMIM MENDELIAN

Familial primary hypomagnesemia with normocalciuria and normocalcemia (FPHNN) is a form of familial primary hypomagnesemia (FPH), characterized by low serum magnesium (Mg) values but inappropriate normal urinary Mg values (i.e. renal hypomagnesemia). The typical symptoms are weakness of the limbs, vertigo, headaches, seizures, brisk tendon reflexes and mild to moderate psychomotor delay.

• Seizures
• Microcephaly
• Ventriculomegaly
• Headache
• Obesity

SOURCES: ORPHANET MENDELIAN

Aminoacylase 1 deficiency (ACY1D) is an inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms.

NEUROLOGICAL CONDITIONS ASSOCIATED WITH AMINOACYLASE 1 DEFICIENCY Is also known as n-acyl-l-amino acid amidohydrolase deficiency|acy1d

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM ORPHANET MESH MENDELIAN

NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, NEUROPATHY, AND DEAFNESS; NEDHND Is also known as myopathy, congenital, with neuropathy and deafness|cmnd

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Scoliosis

SOURCES: OMIM MENDELIAN

Severe X-linked mitochondrial encephalomyopathy is an extremely rare mitochondrial respiratory chain disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting in the two patients reported to date.

SEVERE X-LINKED MITOCHONDRIAL ENCEPHALOMYOPATHY Is also known as mitochondrial encephalomyopathy due to coxpd6|mitochondrial encephalomyopathy due to combined oxidative phosphorylation defect 6|encephalomyopathy, mitochondrial, x-linked

• Seizures
• Global developmental delay
• Generalized hypotonia
• Muscle weakness
• Delayed speech and language development

SOURCES: ORPHANET OMIM MENDELIAN

X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive skeletal muscle disorder characterized by childhood onset of progressive muscle weakness and atrophy primarily affecting the proximal muscles. While onset is usually in childhood, it can range from infancy to adulthood. Many patients lose ambulation and become wheelchair-bound. Other organ systems, including the heart, are clinically unaffected. Muscle biopsy shows intracytoplasmic autophagic vacuoles with sarcolemmal features and a multilayered basal membrane (summary by Ramachandran et al., 2013; Kurashige et al., 2013, and Ruggieri et al., 2015).Danon disease (OMIM ), caused by mutation in the LAMP2 gene (OMIM ) on chromosome Xq24, is a distinct disorder with similar pathologic features.

MYOPATHY, X-LINKED, WITH EXCESSIVE AUTOPHAGY; MEAX Is also known as xmea

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

SOURCES: OMIM MENDELIAN

Congenital myasthenic syndrome-19 is an autosomal recessive disorder resulting from a defect in the neuromuscular junction, causing generalized muscle weakness, exercise intolerance, and respiratory insufficiency. Patients present with hypotonia, feeding difficulties, and respiratory problems soon after birth, but the severity of the weakness and disease course is variable (summary by Logan et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

• Global developmental delay
• Generalized hypotonia
• Micrognathia
• Muscle weakness
• Ptosis

SOURCES: OMIM MENDELIAN

Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003).For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (OMIM ).

MITOCHONDRIAL DNA DEPLETION SYNDROME 4B (MNGIE TYPE); MTDPS4B Is also known as mngie, polg-related|mitochondrial neurogastrointestinal encephalopathy syndrome, polg-related

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN