Delayed speech and language development, and Hepatosplenomegaly

High match ECTODERMAL DYSPLASIA, ANHIDROTIC, WITH T-CELL IMMUNODEFICIENCY, AUTOSOMAL DOMINANT

Mutations in the NFKBIA gene result in functional impairment of NFKB1 (OMIM ), a master transcription factor required for normal activation of immune responses. Interruption of NFKB1 signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection (McDonald et al., 2007).

• Autosomal dominant inheritance
• Growth delay
• Failure to thrive
• Delayed speech and language development
• Tics

SOURCES: MESH MONDO OMIM UMLS

High match STOMATIN-DEFICIENT CRYOHYDROCYTOSIS WITH NEUROLOGIC DEFECTS; SDCHCN

Stomatin-deficient cryohydrocytosis with neurologic defects is an autosomal dominant disorder characterized by delayed psychomotor development, seizures, cataracts, and pseudohyperkalemia resulting from defects in the red blood cell membrane. The disorder combines the neurologic features of Glut1 deficiency syndrome-1 (GLUT1DS1 ), resulting from impaired glucose transport at the blood-brain barrier, and hemolytic anemia/pseudohyperkalemia with stomatocytosis, resulting from a cation leak in erythrocytes (summary by Bawazir et al., 2012).For a discussion of clinical and genetic heterogeneity of red cell stomatocyte disorders, see {194380}.

STOMATIN-DEFICIENT CRYOHYDROCYTOSIS WITH NEUROLOGIC DEFECTS; SDCHCN Is also known as glut1 deficiency syndrome with pseudohyperkalemia and hemolysis, cryohydrocytosis, stomatin-deficient, with mental retardation, seizures, cataracts, and massive hepatosplenomegaly;chc type 2; hereditary cryohydrocytosis type 2; stomatin-deficient cryohydrocytosis; sdchc

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

SOURCES: ORPHANET MONDO MESH OMIM UMLS

High match PHOSPHOGLYCERATE KINASE 1 DEFICIENCY

Phosphoglycerate kinase-1 deficiency is an X-linked recessive condition with a highly variable clinical phenotype that includes hemolytic anemia, myopathy, and neurologic involvement. Patients can express 1, 2, or all 3 of these manifestations (Shirakawa et al., 2006).

PHOSPHOGLYCERATE KINASE 1 DEFICIENCY Is also known as pgk1 deficiency;gsd due to phosphoglycerate kinase 1 deficiency; glycogenosis due to phosphoglycerate kinase 1 deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Ataxia

SOURCES: MESH GARD MONDO OMIM ORPHANET NCIT UMLS

High match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj; CDG2J

COG4-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case to date by seizures, some dysmorphic features, axial hyponia, slight peripheral hypertonia and hyperreflexia.

CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj; CDG2J Is also known as cdg iij;cdgiij;cdg syndrome type iij; cdg-iij; cdg2j; carbohydrate deficient glycoprotein syndrome type iij; congenital disorder of glycosylation type 2j; congenital disorder of glycosylation type iij

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: MONDO GARD SCTID ORPHANET UMLS OMIM

High match MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB

Beta-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal beta-mannosidase activity. The most severely affected patients show developmental delay and mental retardation, but there are differing levels of severity and some patients may have comparatively mild disease (Bedilu et al., 2002) The disorder was first described in goats (Jones and Dawson, 1981), who have a more severe neurodegenerative disorder than that seen in humans.

MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB Is also known as beta-mannosidosis, lysosomal beta-mannosidase deficiency, beta-mannosidase deficiency;beta-mannosidase deficiency

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

SOURCES: OMIM MONDO SCTID MESH DOID NCIT ORPHANET GARD UMLS

High match SIALURIA

Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.

SIALURIA Is also known as sialuria, french type;sialuria, french type

• Autosomal dominant inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Scoliosis

SOURCES: OMIM GARD MONDO ORPHANET DOID

Medium match SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 20; SCAR20

Autosomal recessive spinocerebellar ataxia-20 is a neurodevelopmental disorder characterized by severely delayed psychomotor development with poor or absent speech, wide-based or absent gait, coarse facies, and cerebellar atrophy (summary by Thomas et al., 2014).

SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 20; SCAR20 Is also known as ;autosomal recessive spinocerebellar ataxia type 20; intellectual disability-coarse face-macrocephaly-cerebellar hypoplasia syndrome; scar20

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

SOURCES: MONDO ORPHANET OMIM UMLS DOID

Medium match SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME; SPDRS

Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterized by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss (summary by Fragaki et al., 2013). Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood (summary by Boccuto et al., 2014). Not all patients have overt seizures (Lee et al., 2016).

SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME; SPDRS Is also known as amish infantile epilepsy syndrome, epilepsy syndrome, infantile-onset symptomatic, gm3 synthase deficiency, salt and pepper mental retardation syndrome;infantile-onset symptomatic epilepsy syndrome-developmental stagnation-blindness syndrome

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

SOURCES: OMIM MONDO UMLS ORPHANET SCTID GARD

Medium match MUCOLIPIDOSIS IV; ML4

Mucolipidosis IV is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmologic abnormalities. The lysosomal hydrolases in ML IV are normal, in contrast to most other storage diseases. The disorder results from a defect in transport along the lysosomal pathway, affecting membrane sorting and/or late steps of endocytosis, which causes intracellular accumulation of lysosomal substrates. Over 80% of the patients in whom the diagnosis of ML IV has been made are Ashkenazi Jews, including severely affected and mildly affected patients (Chen et al., 1998).

MUCOLIPIDOSIS IV; ML4 Is also known as ml iv, sialolipidosis;

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

SOURCES: OMIM ORPHANET NCIT SCTID GARD ICD10 MONDO

Medium 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