Delayed speech and language development, and Glioma

Low match NEUROFIBROMATOSIS-NOONAN SYNDROME; NFNS

NEUROFIBROMATOSIS-NOONAN SYNDROME; NFNS Is also known as noonan-neurofibromatosis syndrome, neurofibromatosis with noonan phenotype

• Autosomal dominant inheritance
• Global developmental delay
• Short stature
• Pica
• Scoliosis

SOURCES: OMIM ORPHANET

Low match CHROMOSOME 17q11.2 DELETION SYNDROME, 1.4-MB

Approximately 5 to 20% of all patients with neurofibromatosis type I (OMIM ) carry a heterozygous deletion of approximately 1.4 Mb involving the NF1 gene and contiguous genes lying in its flanking regions (Riva et al., 2000; Jenne et al., 2001), which is caused by nonallelic homologous recombination of NF1 repeats A and C (Dorschner et al., 2000). The 'NF1 microdeletion syndrome' is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, mental retardation, developmental delay, an excessive number of early-onset neurofibromas (Venturin et al., 2004), and an increased risk for malignant peripheral nerve sheath tumors (De Raedt et al., 2003).

CHROMOSOME 17q11.2 DELETION SYNDROME, 1.4-MB Is also known as neurofibromatosis 1 microdeletion syndrome, nf1 microdeletion syndrome, van asperen syndrome;dup(17)(q11.2); grisart-destrée syndrome; trisomy 17q11.2

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

SOURCES: GARD ORPHANET DOID OMIM MONDO

Low match ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL

Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007).The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, non-scarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).

ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL Is also known as ;haberland syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Pica
• Failure to thrive

SOURCES: ORPHANET SCTID MESH GARD OMIM UMLS MONDO NCIT

Low 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 KOOLEN-DE VRIES SYNDROME; KDVS

Koolen-De Vries syndrome is characterized by moderate to severe intellectual disability, hypotonia, friendly demeanor, and highly distinctive facial features, including tall, broad forehead, long face, upslanting palpebral fissures, epicanthal folds, tubular nose with bulbous nasal tip, and large ears. More variable features include cardiac or genitourinary anomalies and seizures (summary by Koolen et al., 2012).

KOOLEN-DE VRIES SYNDROME; KDVS Is also known as chromosome 17q21.31 deletion syndrome, microdeletion 17q21.31 syndrome;del(17)(q21.31); monosomy 17q21.31

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

SOURCES: ORPHANET OMIM

Low match FLOATING-HARBOR SYNDROME; FLHS

Floating-Harbor syndrome is a rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips (Lacombe et al., 1995).Rubinstein-Taybi syndrome (see {180849}), which shows phenotypic overlap with Floating-Harbor syndrome, is caused by mutation in the CREBBP gene (OMIM ), for which SRCAP is a coactivator.

FLOATING-HARBOR SYNDROME; FLHS Is also known as ;

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

SOURCES: MONDO SCTID MESH ORPHANET GARD UMLS OMIM

Low match PARKINSON DISEASE 8, AUTOSOMAL DOMINANT; PARK8

• Autosomal dominant inheritance
• Seizures
• Pica
• Cognitive impairment
• Delayed speech and language development

SOURCES: DOID MONDO UMLS OMIM

Low match MENTAL RETARDATION, X-LINKED 12; MRX12

X-linked intellectual disability-short stature-overweight syndrome is a multiple congenital anomalies syndrome characterized by borderline to severe intellectual disability, speech delay, short stature, elevated body mass index, a pattern of truncal obesity (reported in older males), and variable neurologic features (e.g. hypotonia, tremors, gait disturbances, behavioral problems, and seizure disorders). Less common manifestations include microcephaly, microorchidism and/or microphallus. Dysmorphic features have been reported in some patients but no consitent pattern has been noted.

MENTAL RETARDATION, X-LINKED 12; MRX12 Is also known as mental retardation, x-linked 35;mrx35;

• Intellectual disability
• Seizures
• Short stature
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET MONDO UMLS OMIM

Low match NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 5; NBIA5

NBIA5, sometimes referred to as 'static encephalopathy of childhood with neurodegeneration in adulthood (SENDA),' is an X-linked neurodegenerative disorder characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability. Brain MRI shows iron accumulation in the globus pallidus and substantia nigra. A characteristic finding is T1-weighted hyperintensity surrounding a central band of hypointensity in the substantia nigra. Cerebral and cerebellar atrophy are also observed (summary by Haack et al., 2012 and Saitsu et al., 2013).For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (OMIM ).

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 5; NBIA5 Is also known as beta-propeller protein-associated neurodegeneration;bpan, static encephalopathy of childhood with neurodegeneration in adulthood;senda;bpan; nbia5; neurodegeneration with brain iron accumulation type 5; senda; static encephalopathy of childhood with neurdegeneration in adulthood

• Intellectual disability
• Seizures
• Global developmental delay
• Motor delay
• Spasticity

SOURCES: SCTID DOID ORPHANET GARD OMIM MONDO UMLS

Low match STRIATONIGRAL DEGENERATION, INFANTILE; SNDI

Bilateral striatal necrosis (BSN) encompasses a heterogeneous group of neurologic disorders with different causation. Familial infantile striatal degeneration is rare and can be inherited as an autosomal recessive or mitochondrial (see {500003}) disorder. The familial form has an insidious onset and a slowly progressive course; the sporadic form is associated with acute systemic illness. Many features of BSN overlap with Leigh syndrome (OMIM ) and certain metabolic disorders, including glutaric acidemia I (OMIM ) and methylmalonic aciduria (OMIM ). See also Aicardi-Goutieres syndrome (OMIM ) (Mito et al., 1986; De Meirleir et al., 1995). Genetic Heterogeneity of Stiatonigral DegenerationChildhood-onset striatonigral degeneration (OMIM ) is caused by mutation in the VAC14 gene (OMIM ) on chromosome 16q22.See also adult-onset autosomal dominant striatal degeneration (ADSD ), caused by mutation in the PDE8B gene (OMIM ) on chromosome 5q13.

STRIATONIGRAL DEGENERATION, INFANTILE; SNDI Is also known as infantile bilateral striatal necrosis;ibsn, bilateral striatal necrosis, infantile, striatal degeneration, familial

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Ataxia
• Nystagmus

SOURCES: OMIM ORPHANET