Delayed speech and language development, and Peripheral axonal neuropathy

Medium match LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION; LBSL

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy (Scheper et al., 2007). Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.

LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION; LBSL Is also known as mitochondrial aspartyl-trna synthetase deficiency;lbsl; leukoencephalopathy with brain stem and spinal cord involvement-lactate elevation syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Generalized hypotonia
• Ataxia

SOURCES: MONDO UMLS MESH ORPHANET GARD SCTID OMIM

Medium match MENTAL RETARDATION, AUTOSOMAL DOMINANT 9; MRD9

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: MONDO UMLS OMIM NCIT DOID

Medium match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 6; COXPD6

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.

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 6; COXPD6 Is also known as encephalomyopathy, mitochondrial, x-linked;mitochondrial encephalomyopathy due to coxpd6; mitochondrial encephalomyopathy due to combined oxidative phosphorylation defect 6

• Seizures
• Global developmental delay
• Generalized hypotonia
• Motor delay
• Muscle weakness

SOURCES: MONDO OMIM SCTID UMLS ORPHANET

Medium match SEIZURES, SENSORINEURAL DEAFNESS, ATAXIA, MENTAL RETARDATION, AND ELECTROLYTE IMBALANCE; SESAMES

SeSAME syndrome is characterized by seizures, sensorineural deafness, ataxia, intellectual deficit, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia).

SEIZURES, SENSORINEURAL DEAFNESS, ATAXIA, MENTAL RETARDATION, AND ELECTROLYTE IMBALANCE; SESAMES Is also known as sesame syndrome, epilepsy, ataxia, sensorineural deafness, and tubulopathy, east syndrome;sesame syndrome; seizures-sensorineural deafness-ataxia-intellectual disability-electrolyte imbalance syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: MESH ORPHANET SCTID UMLS GARD OMIM MONDO DOID

Medium match HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES 3; IHPRF3

TBCK-related intellectual disability syndrome is a rare, genetic, syndromic intellectual disability characterized by usually profound intellectual disability with absent speech, severe infantile hypotonia with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset epilepsy, strabismus and post-natal onset of progressive brain atrophy (incl. loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (incl. plagio/brachicephaly, bitemporal narrowing, high-arched eyebrows, high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features.

HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES 3; IHPRF3 Is also known as ;

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Abnormal facial shape

SOURCES: ORPHANET MONDO OMIM UMLS

Medium match NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4; NBIA4

Neurodegeneration with brain iron accumulation-4 (NBIA4) is an autosomal recessive neurodegenerative disorder characterized by progressive spastic paraplegia, parkinsonism unresponsive to L-DOPA treatment, and psychiatric or behavioral symptoms. Other neurologic features, including optic atrophy, eye movement abnormalities, dystonia, dysphagia, dysarthria, and motor axonal neuropathy, may occur. Brain MRI shows T2-weighted hypointensities in the globus pallidus and substantia nigra. Onset is usually in the first 2 decades, but later onset has been reported (summary by Dogu et al., 2013). There is phenotypic variation: some patients may not have extrapyramidal signs and may have muscle weakness and atrophy as well as cognitive impairment or developmental delay (Deschauer et al., 2012)For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (OMIM ).

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4; NBIA4 Is also known as mitochondrial protein-associated neurodegeneration;mpan;mpan; nbia due to c19orf12 mutation; nbia4; neurodegeneration with brain iron accumulation due to c19orf12 mutation; neurodegeneration with brain iron accumulation type 4

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Pica
• Ataxia

SOURCES: OMIM DOID SCTID GARD UMLS ORPHANET MONDO

Medium match HAREL-YOON SYNDROME; HAYOS

Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. Other more variable features such as optic atrophy may also occur. Laboratory studies in some patients show evidence of mitochondrial dysfunction (summary by Harel et al., 2016).

HAREL-YOON SYNDROME; HAYOS Is also known as ;harel-yoon syndrome

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay

SOURCES: ORPHANET OMIM MONDO UMLS

Medium match WIEACKER-WOLFF SYNDROME; WRWF

Wieacker-Wolff syndrome is a severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder (summary by Hirata et al., 2013).

WIEACKER-WOLFF SYNDROME; WRWF Is also known as wieacker syndrome, contractures of feet, muscle atrophy, and oculomotor apraxia, apraxia, oculomotor, with congenital contractures and muscle atrophy, miles-carpenter x-linked mental retardation syndrome;mcs, mental retardation, x-linked, syndromic 4;mrxs4, mental retardation, x-linked, with congenital contractures and low fingertip arches;foot contractures-muscle atrophy-oculomotor apraxia syndrome; wieacker-wolff syndrome

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

SOURCES: ORPHANET OMIM GARD MESH MONDO

Medium match SHORT STATURE, MICROCEPHALY, AND ENDOCRINE DYSFUNCTION; SSMED

In patients with SSMED, short stature and microcephaly are apparent at birth, and there is progressive postnatal growth failure. Endocrine dysfunction, including hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus, is present in affected adults. Progressive ataxia has been reported in some patients, with onset ranging from the second to fifth decade of life. In addition, a few patients have developed tumors, suggesting that there may be a predisposition to tumorigenesis. In contrast to syndromes involving defects in other components of the nonhomologous end-joining (NHEJ) complex (see, e.g., {606593}), no clinically overt immunodeficiency has been observed in SSMED, although laboratory analysis has revealed lymphopenia or borderline leukopenia in some patients (Murray et al., 2015; Bee et al., 2015; de Bruin et al., 2015; Guo et al., 2015).

• Autosomal recessive inheritance
• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: UMLS MONDO OMIM

Low match CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2O; CMT2O

CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2O; CMT2O Is also known as charcot-marie-tooth neuropathy, axonal, type 2o, charcot-marie-tooth disease, axonal, autosomal dominant, type 2o;cmt2o

• Autosomal dominant inheritance
• Motor delay
• Peripheral neuropathy
• Pain
• Gait disturbance

SOURCES: MONDO GARD ORPHANET UMLS DOID OMIM