Delayed speech and language development, and Scarring

Low match LIPOID PROTEINOSIS OF URBACH AND WIETHE

Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane (summary by Hamada et al., 2002 and Hamada et al., 2003).

LIPOID PROTEINOSIS OF URBACH AND WIETHE Is also known as lipoid proteinosis, urbach-wiethe disease, hyalinosis cutis et mucosae;hyalinosis cutis et mucosae; urbach-wiethe disease

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Pica
• High palate

SOURCES: SCTID MESH GARD DOID OMIM NCIT UMLS ORPHANET 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 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 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A

De Barsy syndrome, or autosomal recessive cutis laxa type III (ARCL3), is characterized by cutis laxa, a progeria-like appearance, and ophthalmologic abnormalities (summary by Kivuva et al., 2008).For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see {219100}. Genetic Heterogeneity of de Barsy SyndromeAlso see ARCL3B (OMIM ), caused by mutation in the PYCR1 gene (OMIM ) on chromosome 17q25.

CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A Is also known as de barsy syndrome a, cutis laxa, corneal clouding, and mental retardation, progeroid syndrome of de barsy

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

SOURCES: MONDO OMIM DOID ORPHANET

Low match VESICOURETERAL REFLUX 3; VUR3

• Autosomal dominant inheritance
• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hypoplasia of the corpus callosum

SOURCES: MONDO OMIM UMLS

Low match FOCAL FACIAL DERMAL DYSPLASIA 3, SETLEIS TYPE; FFDD3

The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFFD3 is an autosomal recessive disorder characterized by bitemporal skin lesions with variable facial findings, including thin and puckered periorbital skin, distichiasis and/or absent eyelashes, upslanting palpebral fissures, a flat nasal bridge with a broad nasal tip, large lips, and redundant facial skin (summary by Slavotinek et al., 2013).FFDD2 (OMIM ) is characterized by the same facial features as FFDD3, but the inheritance is autosomal dominant.For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (OMIM ).

FOCAL FACIAL DERMAL DYSPLASIA 3, SETLEIS TYPE; FFDD3 Is also known as setleis syndrome, bitemporal forceps marks syndrome, facial ectodermal dysplasia, focal facial dermal dysplasia, type ii, formerly

• Autosomal recessive inheritance
• Global developmental delay
• Depressed nasal bridge
• Tics
• Anal atresia

SOURCES: OMIM

Low match EHLERS-DANLOS SYNDROME, MUSCULOCONTRACTURAL TYPE, 2; EDSMC2

The musculocontractural type of Ehlers-Danlos syndrome is characterized by progressive multisystem fragility-related manifestations, including joint dislocations and deformities; skin hyperextensibility, bruisability, and fragility, with recurrent large subcutaneous hematomas; cardiac valvular, respiratory, gastrointestinal, and ophthalmologic complications; and myopathy, featuring muscle hypoplasia, muscle weakness, and an abnormal muscle fiber pattern in histology in adulthood, resulting in gross motor developmental delay (summary by Muller et al., 2013).For a discussion of genetic heterogeneity of the musculocontractural type of Ehlers-Danlos syndrome, see EDSMC1 (OMIM ).

• Autosomal recessive inheritance
• Abnormal facial shape
• Muscle weakness
• Myopathy
• High palate

SOURCES: MONDO UMLS OMIM

Low match BETHLEM MYOPATHY 1; BTHLM1

Bethlem myopathy is a benign autosomal dominant form of slowly progressive muscular dystrophy.

BETHLEM MYOPATHY 1; BTHLM1 Is also known as bethlem myopathy, myopathy, benign congenital, with contractures, muscular dystrophy, benign congenital;benign autosomal dominant myopathy

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Generalized hypotonia
• Motor delay
• Muscle weakness

SOURCES: UMLS SCTID OMIM ORPHANET MONDO

Low match FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, 3A, WITH OR WITHOUT EXTRAOCULAR INVOLVEMENT; CFEOM3A

Congenital fibrosis of the extraocular muscles (CFEOM) encompasses several different inherited strabismus syndromes characterized by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. If all affected members of a family have classic CFEOM with bilateral involvement and inability to raise the eyes above midline, the phenotype is classified as CFEOM1 (OMIM ). CFEOM2 (OMIM ) shows autosomal recessive inheritance. CFEOM3 is characterized by autosomal dominant inheritance of a more variable phenotype than classic CFEOM1. Individuals with CFEOM3 may not have bilateral involvement, may be able to raise the eyes above midline, or may not have blepharoptosis (reviews by Yamada et al., 2004 and Heidary et al., 2008).Yamada et al. (2003) concluded that CFEOM3 is a relatively rare form of CFEOM. Genetic Heterogeneity of CFEOM3The CFEOM3 phenotype is genetically heterogeneous; see also CFEOM3B (OMIM ), caused by mutation in the KIF21A gene on chromosome 12q12, and CFEOM3C (OMIM ), which maps to chromosome 13q.

FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, 3A, WITH OR WITHOUT EXTRAOCULAR INVOLVEMENT; CFEOM3A Is also known as feom3 locus

• Autosomal dominant inheritance
• Global developmental delay
• Ptosis
• Flexion contracture
• Peripheral neuropathy

SOURCES: MESH OMIM MONDO UMLS