Delayed speech and language development, and Telangiectasia

Low match PROLIDASE DEFICIENCY

Prolidase deficiency is a rare autosomal recessive multisystem disorder associated with massive imidodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. The disorder is clinically heterogeneous and severity varies widely. Features include chronic, slowly healing ulcerations, mainly on the legs and feet. The ulcers are often preceded by other dermatologic manifestations that may occur anywhere and include erythematous papular eruptions, telangiectasias with pruritus and photosensitivity, impetigo-like eruptions, pruritic eczematous lesions, and necrotic papules. Mild to severe mental retardation is often a feature, and recurrent respiratory tract infections, sometimes fatal, are common. Facial dysmorphism may include low hairline and hirsutism, saddle nose, ocular hypertelorism, micrognathia, a high-arched palate, mandibular protrusion, and exophthalmos. Clinical manifestations are usually detectable after birth or in early childhood, but late-onset cases have been reported (summary by Lupi et al., 2008).

PROLIDASE DEFICIENCY Is also known as ;hyperimidodipeptiduria

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Hearing impairment
• Hypertelorism

SOURCES: GARD MONDO ORPHANET MESH OMIM NCIT SCTID

Low match AGAMMAGLOBULINEMIA, X-LINKED; XLA

X-linked agammaglobulinemia is an immunodeficiency characterized by failure to produce mature B lymphocytes and associated with a failure of Ig heavy chain rearrangement. The defect in this disorder resides in BTK, also known as BPK or ATK, a key regulator in B-cell development (Rawlings and Witte, 1994). The X-linked form accounts for approximately 85 to 90% of cases of the disorder. Also see {300310}. The remaining 15% of cases constitute a heterogeneous group of autosomal disorders (Lopez Granados et al., 2002; Ferrari et al., 2007). See agammaglobulinemia-1 (AGM1 ) for a discussion of genetic heterogeneity of the autosomal forms of agammaglobulinemia.

AGAMMAGLOBULINEMIA, X-LINKED; XLA Is also known as bruton-type agammaglobulinemia, agammaglobulinemia, x-linked, type 1;agmx1, immunodeficiency 1;imd1;btk-deficiency; bruton type agammaglobulinemia

• Short stature
• Hearing impairment
• Ataxia
• Failure to thrive
• Sensorineural hearing impairment

SOURCES: SCTID OMIM ORPHANET

Low match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie; CDG1E

Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin.For a general discussion of CDGs, see CDG Ia (OMIM ) and CDG Ib (OMIM ).

CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ie; CDG1E Is also known as cdg ie;cdgie;cdg syndrome type ie; cdg-ie; cdg1e; carbohydrate deficient glycoprotein syndrome type ie; congenital disorder of glycosylation type 1e; congenital disorder of glycosylation type ie; dol-p-mannosyltransferase deficiency

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

SOURCES: NCIT SCTID ORPHANET MONDO GARD UMLS OMIM MESH

Low match BANNAYAN-RILEY-RUVALCABA SYNDROME; BRRS

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare congenital disorder characterized by hamartomatous intestinal polyposis, lipomas, macrocephaly and genital lentiginosis.

BANNAYAN-RILEY-RUVALCABA SYNDROME; BRRS Is also known as bannayan-zonana syndrome;bzs, riley-smith syndrome, ruvalcaba-myhre-smith syndrome;rmss, macrocephaly, pseudopapilledema, and multiple hemangiomata, macrocephaly, multiple lipomas, and hemangiomata;brrs; myhre-riley-smith syndrome

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

SOURCES: DOID GARD NCIT MONDO SCTID ORPHANET OMIM ICD10

Low match CRANIOSYNOSTOSIS 4; CRS4

Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-4 includes lambdoid, sagittal, metopic, coronal, and multisuture forms.For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (OMIM ).

• Autosomal dominant inheritance
• Hypertelorism
• Ptosis
• Depressed nasal bridge
• Delayed speech and language development

SOURCES: MONDO UMLS OMIM

Low match ATAXIA-TELANGIECTASIA-LIKE DISORDER 2; ATLD2

Ataxia-telangiectasia-like disorder-2 is an autosomal recessive syndrome resulting from defects in DNA excision repair. Affected individuals have a neurodegenerative phenotype characterized by developmental delay, ataxia, and sensorineural hearing loss. Other features include short stature, cutaneous and ocular telangiectasia, and photosensitivity (summary by Baple et al., 2014).For a discussion of genetic heterogeneity of ATLD, see ATLD1 (OMIM ).

ATAXIA-TELANGIECTASIA-LIKE DISORDER 2; ATLD2 Is also known as ;

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

SOURCES: UMLS MONDO ORPHANET OMIM

Low match ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY TYPE 1

Alpha-N-acetylgalactosaminidase (NAGA) deficiency type 1 is a very rare and severe type of NAGA deficiency (see this term) characterized by infantile neuroaxonal dystrophy.

ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY TYPE 1 Is also known as naga deficiency type 1; schindler disease type 1

• Seizures
• Global developmental delay
• Hearing impairment
• Nystagmus
• Strabismus

SOURCES: ORPHANET

Low match SOTOS SYNDROME 2; SOTOS2

Malan overgrowth syndrome is a multiple congenital anomalies syndrome characterized by moderate postnatal overgrowth, macrocephaly, craniofacial dysmorphism (including high forehead and anterior hairline, downslanting palpebral fissures, prominent chin), developmental delay, and intellectual disability. Additional variable manifestations include unusual behavior, with or without autistic traits, as well as ocular (e.g. strabismus, nystagmus, optic disc pallor/hypoplasia), gastrointestinal (e.g. vomiting, chronic diarrhea, constipation), musculoskeletal (e.g. scoliosis and pectus excavatum), hand/foot (e.g. long, tapered fingers) and central nervous system (e.g. slightly enlarged ventricles) anomalies.

SOTOS SYNDROME 2; SOTOS2 Is also known as malan syndrome;sotos syndrome 2

• Autosomal dominant inheritance
• Intellectual disability
• Generalized hypotonia
• Scoliosis
• Nystagmus

SOURCES: ORPHANET UMLS OMIM MONDO

Low match IMMUNODEFICIENCY 49; IMD49

IMMUNODEFICIENCY 49; IMD49 Is also known as severe combined immunodeficiency, t cell-negative, b cell-positive, nk cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities, scid, t cell-negative, b cell-positive, nk cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities

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

SOURCES: UMLS MONDO OMIM

Low match GM1-GANGLIOSIDOSIS, TYPE III

GM1-gangliosidosis type III is an autosomal recessive lysosomal storage disorder characterized by neurodegeneration and mild skeletal changes. Age at onset ranges from 3 to 30 years. The disorder is less severe than GM1-gangliosidosis types I and II (OMIM ). Type III shows extreme clinical variability, with some patients having only focal neurologic signs, such as dystonia, and others having more severe involvement with extrapyramidal signs and mental retardation. GLB1 enzymatic activity usually ranges from approximately 4 to 10% of control values (Suzuki et al., 2001).

GM1-GANGLIOSIDOSIS, TYPE III Is also known as gangliosidosis, generalized gm1, adult type, gangliosidosis, generalized gm1, chronic type, gangliosidosis, generalized gm1, type iii, gangliosidosis, generalized gm1, type 3;adult-onset gm1 gangliosidosis

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Short stature
• Scoliosis

SOURCES: OMIM GARD UMLS SCTID ORPHANET MONDO