Ataxia, and Triangular face

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

X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.

X-LINKED INTELLECTUAL DISABILITY-CEREBELLAR HYPOPLASIA SYNDROME Is also known as oligophrenin-1 syndrome|ophn1 syndrome|mental retardation, x-linked 60, formerly|mrx60, formerly

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

SOURCES: OMIM ORPHANET MESH MENDELIAN

Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay. Affected individuals have characteristic dysmorphic facial features and persistently large head, but increased birth weight normalizes with age. Additional neurologic features, including seizures, hypotonia, and gait ataxia, may also occur. Patients show severe intellectual impairment (summary by Ortega-Recalde et al., 2015).

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

SOURCES: OMIM MENDELIAN

Phosphoribosylpyrophosphate synthetase I superactivity is an X-linked inborn error of metabolism in which increased enzyme activity is associated with hyperuricemia and gout. Some affected individuals have neurodevelopmental abnormalities, particularly sensorineural deafness (Becker et al., 1988; Roessler et al., 1993).Although different kinetic defects affecting the PRPS1 enzyme have been identified in this disorder, the common pathway involves increased synthesis of phosphoribosylpyrophosphate (PRPP), which leads to increased uric acid and purine production (Becker, 2001).

PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE SUPERACTIVITY Is also known as prps1 superactivity

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

SOURCES: OMIM ORPHANET MENDELIAN

Hypotonia, ataxia, and delayed development syndrome (HADDS) is a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia. Some patients may have urogenital abnormalities (summary by Sleven et al., 2017).

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

SOURCES: OMIM MENDELIAN

Mevalonic aciduria (MVA) is a rare, very severe form of mevalonate kinase deficiency (MKD; see this term) characterized by dysmorphic features, failure to thrive, psychomotor delay, ocular involvement, hypotonia, progressive ataxia, myopathy, and recurrent inflammatory episodes.

MEVALONIC ACIDURIA Is also known as mva|complete mevalonate kinase deficiency

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

SOURCES: OMIM ORPHANET MENDELIAN

Andersen-Tawil syndrome is an autosomal dominant multisystem channelopathy characterized by periodic paralysis, ventricular arrhythmias, and distinctive dysmorphic facial or skeletal features. Hypoplastic kidney and valvular heart disease have also been reported. The disorder shows marked intrafamilial variability and incomplete penetrance (summary by Davies et al., 2005).

ANDERSEN CARDIODYSRHYTHMIC PERIODIC PARALYSIS Is also known as ats|andersen syndrome|long qt syndrome 7|periodic paralysis, potassium-sensitive cardiodysrhythmic type|lqt7|andersen-tawil syndrome

• Seizures
• Short stature
• Microcephaly
• Scoliosis
• Ataxia

SOURCES: OMIM MENDELIAN

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).

• Global developmental delay
• Short stature
• Hearing impairment
• Microcephaly
• Ataxia

SOURCES: OMIM MENDELIAN

ALAGILLE SYNDROME DUE TO A NOTCH2 POINT MUTATION Is also known as syndromic bile duct paucity due to a notch2 point mutation|arteriohepatic dysplasia due to a notch2 point mutation|alagille-watson syndrome due to a notch2 point mutation

• Hypertelorism
• Failure to thrive
• Cognitive impairment
• Hypertension
• Hepatomegaly

SOURCES: ORPHANET OMIM MENDELIAN