Delayed speech and language development, and Myeloid leukemia

Medium match NOONAN SYNDROME 6; NS6

• Intellectual disability
• Short stature
• Generalized hypotonia
• Pica
• Hearing impairment

SOURCES: MESH GARD MONDO DOID OMIM UMLS

Medium match MENTAL RETARDATION, X-LINKED, SYNDROMIC, NASCIMENTO TYPE; MRXSN

X-linked intellectual disability, Nascimento type is a rare X-linked intellectual disability syndrome characterized by intellectual disability (with severe speech impairment), a myxedematous appearance, dysmorphic facial features (including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth with everted lower lip and downturned lip corners), low posterior hairline, short, broad neck, marked general hirsutism and abnormal hair whorls, skin changes (e.g. dry skin or hypopigmented spots), widely spaced nipples, obesity, micropenis, onychodystrophy and seizures.

MENTAL RETARDATION, X-LINKED, SYNDROMIC, NASCIMENTO TYPE; MRXSN Is also known as mental retardation, x-linked, syndromic 30;mrxs30;x-linked intellectual disability-nail dystrophy-seizures syndrome

• Intellectual disability
• Seizures
• Depressed nasal bridge
• Macrocephaly
• Short neck

SOURCES: ORPHANET UMLS OMIM MONDO DOID

Medium match NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MYELOMONOCYTIC LEUKEMIA; NSLL

Noonan syndrome-like disorder is a developmental disorder resembling Noonan syndrome (NS1 ) and characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, and ectodermal and musculoskeletal anomalies. There is extensive phenotypic heterogeneity and variable expressivity (summary by Martinelli et al., 2010). Patients with heterozygous germline CBL mutations have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia (JMML ), as also seen in patients with Noonan syndrome (summary by Niemeyer et al., 2010).

NOONAN SYNDROME-LIKE DISORDER WITH OR WITHOUT JUVENILE MYELOMONOCYTIC LEUKEMIA; NSLL Is also known as cbl syndrome, cbl mutation-associated syndrome;cbl syndrome; noonan syndrome-like disorder with jmml

• Autosomal dominant inheritance
• Global developmental delay
• Short stature
• Generalized hypotonia
• Pica

SOURCES: MONDO OMIM ORPHANET UMLS

Medium match ACHONDROPLASIA; ACH

Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand (summary by Bellus et al., 1995).

• Autosomal dominant inheritance
• Short stature
• Generalized hypotonia
• Pica
• Hearing impairment

SOURCES: ICD10 NCIT DOID MESH GARD MONDO OMIM

Low match PRADER-WILLI SYNDROME; PWS

Prader-Willi syndrome is characterized by diminished fetal activity, obesity, muscular hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet. It can be considered to be an autosomal dominant disorder and is caused by deletion or disruption of a gene or several genes on the proximal long arm of the paternal chromosome 15 or maternal uniparental disomy 15, because the gene(s) on the maternal chromosome(s) 15 are virtually inactive through imprinting. Horsthemke and Wagstaff (2008) provided a detailed review of the mechanisms of imprinting of the Prader-Willi/Angelman syndrome (OMIM ) region.See also the chromosome 15q11-q13 duplication syndrome (OMIM ), which shows overlapping clinical features.

PRADER-WILLI SYNDROME; PWS Is also known as prader-labhart-willi syndrome

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

SOURCES: OMIM

Low match MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 3; MVA3

MVA3 is an autosomal recessive disorder resulting from errors in chromosome segregation. Most affected individuals develop early-onset Wilms tumor and show either aneuploidy or premature chromatid separation in cells. Some patients may have additional developmental features, such as microcephaly, growth retardation, or developmental delay (summary by Yost et al., 2017).For a discussion of genetic heterogeneity of MVA, see MVA1 (OMIM ).

• Seizures
• Global developmental delay
• Short stature
• Microcephaly
• Growth delay

SOURCES: OMIM

Low match NOONAN SYNDROME 3; NS3

Noonan syndrome is an autosomal dominant dysmorphic syndrome characterized primarily by dysmorphic facial features, cardiac abnormalities, and short stature, among other features (summary by Shah et al., 1999).For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (OMIM ), which is caused by mutations in the PTPN11 gene (OMIM ). Approximately 50% of cases of Noonan syndrome are caused by mutations in PTPN11.

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

SOURCES: MESH GARD MONDO UMLS OMIM DOID

Low match 3-METHYLGLUTACONIC ACIDURIA WITH CATARACTS, NEUROLOGIC INVOLVEMENT, AND NEUTROPENIA; MEGCANN

3-Methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) is an autosomal recessive inborn error of metabolism characterized primarily by increased levels of 3-methylglutaconic acid (3-MGA) associated with neurologic deterioration and neutropenia. The phenotype is highly variable: most patients have infantile onset of a progressive encephalopathy with various movement abnormalities and delayed psychomotor development, although rare patients with normal neurologic development have been reported. Other common, but variable, features include cataracts, seizures, and recurrent infections (summary by Wortmann et al., 2015 and Saunders et al., 2015).For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (OMIM ).

3-METHYLGLUTACONIC ACIDURIA WITH CATARACTS, NEUROLOGIC INVOLVEMENT, AND NEUTROPENIA; MEGCANN Is also known as 3-methylglutaconic aciduria, type vii;mgca7;3-methylglutaconic aciduria-cataract-neurologic involvement-neutropenia syndrome; mga7

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

SOURCES: DOID EFO ORPHANET UMLS OMIM MONDO

Low match SHWACHMAN-DIAMOND SYNDROME; SDS

Shwachman-Diamond syndrome is a multisystem autosomal recessive disorder characterized by exocrine pancreatic dysfunction, bony metaphyseal dysostosis, and varying degrees of marrow dysfunction with cytopenias. Myelodysplastic syndrome and acute myeloid leukemia occur in up to one third of patients (summary by Dror and Freedman, 1999).For a review of Shwachman-Diamond syndrome, see Dror and Freedman (2002).

SHWACHMAN-DIAMOND SYNDROME; SDS Is also known as pancreatic insufficiency and bone marrow dysfunction, shwachman-bodian syndrome, lipomatosis of pancreas, congenital;pancreatic insufficiency and bone marrow dysfunction; sds; shwachman syndrome; shwachman-bodian-diamond syndrome

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

SOURCES: ORPHANET UMLS OMIM SCTID MONDO

Low match DYSKERATOSIS CONGENITA, X-LINKED; DKCX

Dyskeratosis congenita is classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa. It is characterized by short telomeres. Progressive bone marrow failure occurs in over 80% of cases and is the main cause of early mortality. The phenotype is highly variable, and affected individuals may have multiple additional features, including pulmonary fibrosis, liver cirrhosis, premature hair loss and/or graying, osteoporosis, atresia of the lacrimal ducts, and learning difficulties. Males may have testicular atrophy. Predisposition to malignancy is an important feature. The disorder is caused by defects in the maintenance of telomeres (summary by Kirwan and Dokal, 2008).Hoyeraal-Hreidarsson syndrome (HHS) refers to a clinically severe variant of DKC that is characterized by multisystem involvement and early onset in utero. Patients with HHS show intrauterine growth retardation, microcephaly, delayed development, and bone marrow failure resulting in immunodeficiency, cerebellar hypoplasia, and sometimes enteropathy. Death often occurs in childhood (summary by Walne et al., 2013).For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (OMIM ).

DYSKERATOSIS CONGENITA, X-LINKED; DKCX Is also known as zinsser-cole-engman syndrome;progressive pancytopenia-immunodeficiency-cerebellar hypoplasia syndrome

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

SOURCES: ORPHANET OMIM GARD SCTID MESH MONDO