Delayed speech and language development, and Hyperhidrosis

Medium match HYPOTRICHOSIS 12; HYPT12

• Autosomal dominant inheritance
• Intellectual disability
• Alopecia
• Hyperhidrosis
• Abnormality of the nervous system

SOURCES: MONDO DOID OMIM UMLS

Medium match EPISODIC ATAXIA TYPE 1

Episodic ataxia type 1 (EA1) is a frequent form of Hereditary episodic ataxia (EA; see this term) characterized by brief episodes of ataxia, neuromyotonia, and continuous interictal myokymia.

EPISODIC ATAXIA TYPE 1 Is also known as episodic ataxia with myokymia

• Scoliosis
• Motor delay
• Delayed speech and language development
• Dysarthria
• Cerebellar atrophy

SOURCES: ORPHANET

Medium match SEGAWA SYNDROME, AUTOSOMAL RECESSIVE

Segawa syndrome is an autosomal recessive neurologic disorder characterized by onset in infancy of dopa-responsive dystonia. There are 2 main phenotypes: one is a severe complex encephalopathy apparent in the perinatal period, with diurnal fluctuations and autonomic disturbances, and the other shows a less severe course with onset in the first year of life of a progressive hypokinetic-rigid syndrome and generalized dystonia. The less severe type shows a better response to levodopa compared to the more severe type (summary by Stamelou et al., 2012).See also infantile parkinsonism-dystonia syndrome (OMIM ), caused by mutation in the SLC6A3 gene (OMIM ).

SEGAWA SYNDROME, AUTOSOMAL RECESSIVE Is also known as parkinsonism, infantile, autosomal recessive, dystonia, dopa-responsive, autosomal recessive, dopa-responsive dystonia, autosomal recessive, tyrosine hydroxylase deficiency;autosomal recessive segawa syndrome; dyt5b; tyrosine hydroxylase deficiency; tyrosine hydroxylase-deficient dopa-responsive dystonia

• Autosomal recessive inheritance
• Generalized hypotonia
• Pica
• Ataxia
• Motor delay

SOURCES: OMIM ORPHANET

Medium match ALACRIMA, ACHALASIA, AND MENTAL RETARDATION SYNDROME; AAMR

Alacrima, achalasia, and mental retardation syndrome (AAMR) is an autosomal recessive disorder characterized by onset of these 3 main features at birth or in early infancy. More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome (OMIM ), but patients with AAMR do not have adrenal insufficiency (summary by Koehler et al., 2013).See also {300858} for a phenotypically similar disorder that shows X-linked inheritance.

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM UMLS GARD MONDO

Medium match DYSTONIA, DOPA-RESPONSIVE, DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY

SPR deficiency results in neurologic deterioration due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Clinically, affected individuals show an L-DOPA-responsive, diurnally fluctuating movement disorder usually associated with cognitive delay and severe neurologic dysfunction. BH4 is a required cofactor for the synthesis of the neurotransmitters dopamine and serotonin. BH4 is also a required cofactor for phenylalanine hydroxylase (PAH ), but patients with SPR deficiency do not exhibit overt hyperphenylalaninemia. The lack of hyperphenylalaninemia distinguishes SPR deficiency from other disorders of BH4 synthesis (see, e.g., HPABH4A, {261640}). However, the neurologic phenotype of SPR deficiency resembles the other BH4-deficient disorders (summary by Bonafe et al., 2001 and Friedman et al., 2012).Another form of dopa-responsive dystonia (DTY5 ) is caused by mutation in the gene encoding GTP cyclohydrolase I (GCH1 ), which is also a component of the biopterin synthetic pathway.

DYSTONIA, DOPA-RESPONSIVE, DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY Is also known as sepiapterin reductase deficiency;srd, spr deficiency;autosomal recessive sepiapterin reductase-deficient drd; drd due to srd; spr deficiency; sepiapterin reductase deficiency

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

SOURCES: UMLS DOID SCTID ORPHANET MONDO MESH OMIM GARD

Medium match TYROSINEMIA, TYPE II; TYRSN2

Tyrosinemia type II is an autosomal recessive disorder characterized by keratitis, painful palmoplantar hyperkeratosis, mental retardation, and elevated serum tyrosine levels. The disorder is caused by deficiency of hepatic tyrosine aminotransferase (Natt et al., 1992).

TYROSINEMIA, TYPE II; TYRSN2 Is also known as richner-hanhart syndrome, tyrosine aminotransferase deficiency, tat deficiency, tyrosine transaminase deficiency, keratosis palmoplantaris with corneal dystrophy, oregon type tyrosinemia, tyrosinosis, oculocutaneous type;keratosis palmoplantaris-corneal dystrophy syndrome; oculocutaneous tyrosinemia; richner-hanhart syndrome; tyrosinemia due to tat deficiency; tyrosinemia due to tyrosine aminotransferase deficiency; tyrosinemia type ii

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Pica
• Microcephaly

SOURCES: NCIT DOID MONDO OMIM GARD SCTID ORPHANET

Medium match NEURODEVELOPMENTAL DISORDER WITH PROGRESSIVE MICROCEPHALY, SPASTICITY, AND BRAIN ANOMALIES; NDMSBA

NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy. Some patients die in early childhood (summary by Falik Zaccai et al., 2017 and Hall et al., 2017).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM UMLS

Medium match SCHAAF-YANG SYNDROME; SHFYNG

SHFYNG syndrome is an autosomal dominant multisystem disorder characterized by delayed psychomotor development, intellectual disability (ID), hypotonia, and behavioral abnormalities. Additional features include contractures, feeding difficulties, and variable dysmorphic facial features. The severity of the disorder is highly variable: some patients may die in utero with fetal akinesia, whereas others can live with moderate disability. Individuals are affected only if the mutation occurs on the paternal allele, since MAGEL2 is a maternally imprinted gene (summary by Fountain et al., 2017)

SCHAAF-YANG SYNDROME; SHFYNG Is also known as prader-willi-like syndrome;pwls;pws due to a point mutation; schaaf-yang syndrome

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

SOURCES: OMIM ORPHANET UMLS MONDO GARD

Medium match CAREY-FINEMAN-ZITER SYNDROME; CFZS

Carey-Fineman-Ziter syndrome (CFZS) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. More variable features include dysmorphic facial features, brain abnormalities, and intellectual disability. It has been postulated that many clinical features in CFZS may be secondary effects of muscle weakness during development or brainstem anomalies (summary by Pasetti et al., 2016).Di Gioia et al. (2017) determined that CFZS represents a slowly progressive congenital myopathy resulting from a defect in myoblast fusion.

CAREY-FINEMAN-ZITER SYNDROME; CFZS Is also known as myopathy, congenital nonprogressive, with moebius sequence and robin sequence;myopathy-moebius-robin syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: UMLS ORPHANET SCTID DOID GARD MESH MONDO OMIM

Medium match GLASS SYNDROME; GLASS

Glass syndrome is characterized by intellectual disability of variable severity and dysmorphic facial features, including micrognathia, downslanting palpebral fissures, cleft palate, and crowded teeth. Additional features may include seizures, joint laxity, arachnodactyly, and happy demeanor (summary by Glass et al., 1989; Urquhart et al., 2009; Rainger et al., 2014).

GLASS SYNDROME; GLASS Is also known as chromosome 2q32-q33 deletion syndrome;2q32-q33 microdeletion syndrome; del(2)(q32); del(2)(q32q33); monosomy 2q32; monosomy 2q32-q33; monosomy 2q32q33

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

SOURCES: OMIM ORPHANET GARD DOID UMLS MONDO SCTID MESH