Cleft palate, and Distal sensory impairment

Hereditary neuropathy with or without age-related macular degeneration is a complex autosomal dominant syndrome characterized by a variable peripheral neuropathy resembling demyelinating Charcot-Marie-Tooth disease (see, e.g., CMT1A, {118220}) and/or axonal CMT (see, e.g., CMT2A1, {118210}) with sensorimotor impairment mainly of the distal lower extremities, or spinal CMT, also known as distal hereditary motor neuropathy (see, e.g., HMN1; {182960}) with intact sensation. Age-related macular degeneration, if present, shows very late onset in the seventies or eighties. In addition, some patients may show hyperelasticity of the skin or joints. The age at onset of neuropathy and severity of the disorder is highly variable, even within families (summary by Auer-Grumbach et al., 2011).For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see {603075}.

• Muscle weakness
• High palate
• Peripheral neuropathy
• Skeletal muscle atrophy
• Abnormality of the skeletal system

SOURCES: OMIM MESH MENDELIAN

• Seizures
• Hearing impairment
• Ataxia
• Nystagmus
• Sensorineural hearing impairment

SOURCES: OMIM MENDELIAN

Yuan-Harel-Lupski syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and early-onset peripheral neuropathy. The disorder comprises features of both demyelinating Charcot-Marie-Tooth disease type 1A (CMT1A ), which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome (PTLS ), which results from duplication of a slightly proximal region on 17p11.2 that includes the RAI1 gene. These 2 loci are about 2.5 Mb apart. The resultant YUHAL phenotype may be more severe in comparison to the individual contributions of each gene, with particularly early onset of peripheral neuropathy and features of both central and peripheral nervous system involvement (summary by Yuan et al., 2015).

PMP22-RAI1 CONTIGUOUS GENE DUPLICATION SYNDROME Is also known as trisomy 17p11.2-p12|dup(17)(p11.2p12)|trisomy 17p11.2p12|yuan-harel-lupski syndrome|17p11.2p12 microduplication syndrome

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Failure to thrive
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

Autosomal dominant Charcot-Marie-Tooth disease type 2E (CMT2E) is a form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. CMT2E onset is in the first to 6th decade with a gait anomaly and a leg weakness that reaches the arms secondarily. Tendon reflexes are reduced or absent and, after years, all patients have a pes cavus. Other signs may be present, including hearing loss and postural tremor.

AUTOSOMAL DOMINANT CHARCOT-MARIE-TOOTH DISEASE TYPE 2E Is also known as cmt2e|charcot-marie-tooth neuropathy, type 2e

• Generalized hypotonia
• Hearing impairment
• Scoliosis
• Muscle weakness
• Ptosis

SOURCES: MESH ORPHANET OMIM MENDELIAN

Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they may show abnormal movements, such as ataxia, dysmetria, and myoclonus. The most severely affected patients are hypotonic at birth and die in infancy (summary by Abrams et al., 2015 and Wan et al., 2016).For a general phenotypic description and a discussion of genetic heterogeneity of HMSN6, see HMSN6A (OMIM ).

NEUROPATHY, HEREDITARY MOTOR AND SENSORY, TYPE VIB; HMSN6B Is also known as hmsn vib|charcot-marie-tooth disease, type 6b|cmt6b

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

SOURCES: OMIM MENDELIAN

MITOCHONDRIAL MYOPATHY-CEREBELLAR ATAXIA-PIGMENTARY RETINOPATHY SYNDROME Is also known as mitochondrial myopathy-cerebellar atrophy-pigmentary retinopathy syndrome

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant form of recurrent focal neuropathy characterized clinically by acute, recurrent episodes of brachial plexus neuropathy with muscle weakness and atrophy preceded by severe pain in the affected arm.

AMYOTROPHY, HEREDITARY NEURALGIC; HNA Is also known as neuritis with brachial predilection|napb|amyotrophy, hereditary neuralgic, with predilection for brachial plexus|brachial plexus neuropathy, hereditary

• Short stature
• Muscle weakness
• Abnormal facial shape
• Cleft palate
• Pain

SOURCES: OMIM MENDELIAN

HSN2C is an autosomal recessive disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs (summary by Riviere et al., 2011).For a discussion of genetic heterogeneity of HSN, see HSAN1 (OMIM ).

• Global developmental delay
• Short stature
• Muscle weakness
• Peripheral neuropathy
• Areflexia

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal dominant Charcot-Marie-Tooth disease, type 2K (CMT2K) is an axonal CMT peripheral sensorimotor polyneuropathy.

AUTOSOMAL DOMINANT CHARCOT-MARIE-TOOTH DISEASE TYPE 2K Is also known as cmt2k

• Motor delay
• Skeletal muscle atrophy
• Gait disturbance
• Arrhythmia
• Proximal muscle weakness

SOURCES: ORPHANET MENDELIAN

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by variable intellectual deficit, sleep disturbance, craniofacial and skeletal anomalies, psychiatric disorders, and speech and motor delay.

SMITH-MAGENIS SYNDROME Is also known as 17p11.2 microdeletion syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Microcephaly

SOURCES: ORPHANET MENDELIAN