Delayed speech and language development, and Epidermal acanthosis

Medium match INSULIN-LIKE GROWTH FACTOR I, RESISTANCE TO; IGF1RES

Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).

INSULIN-LIKE GROWTH FACTOR I, RESISTANCE TO; IGF1RES Is also known as somatomedin, end-organ insensitivity to, somatomedin-c, resistance to, igf-i resistance;resistance to igf-1

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

SOURCES: ORPHANET OMIM MONDO UMLS GARD SCTID

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

Medium 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

Medium match COSTELLO SYNDROME; CSTLO

Costello syndrome is a rare multiple congenital anomaly syndrome associated in all cases with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. Facial warts, particularly nasolabial, are often present in childhood (Kerr et al., 2006).In patients with a clinical diagnosis of Costello syndrome, Zenker et al. (2007) identified mutations in the KRAS gene, but noted that these patients may later develop features of CFC syndrome. In either case, the findings underscore the central role of Ras in the pathogenesis of these phenotypically related disorders (Zenker et al., 2007). However, Kerr et al. (2008) commented that the diagnosis of Costello syndrome should only be used to refer to patients with mutations in the HRAS gene.

COSTELLO SYNDROME; CSTLO Is also known as faciocutaneoskeletal syndrome, fcs syndrome;fcs syndrome; faciocutaneoskeletal syndrome

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

SOURCES: DOID OMIM MONDO GARD SCTID ORPHANET MESH UMLS NCIT

Medium match NEVUS, EPIDERMAL

Epidermal nevi are congenital lesions that affect about 1 in 1,000 people. They appear at or shortly after birth as localized epidermal thickening with hyperpigmentation that frequently follow the lines of Blaschko, suggesting that they result from postzygotic somatic mutation in the skin (Paller et al., 1994).A rare subgroup of epidermal nevi is clinically indistinguishable from other epidermal nevi, but displays histopathologic features typical of epidermolytic hyperkeratosis (see EHK, {113800}), and patients with this type of epidermal nevi sometimes have offspring with generalized EHK (Paller et al., 1994).Woolly hair nevus is a rare condition characterized by the development of woolly hair in a restricted area on the scalp, either present at birth or becoming evident later in life when scalp hair begins to grow. Woolly hair nevus can be an isolated finding or can occur in association with additional ectodermal defects; epidermal nevi have been reported in association with woolly hair nevi (summary by Ramot and Zlotogorski, 2015).Nevus sebaceous, a benign congenital skin lesion that preferentially affects the scalp and face, is characterized by hairless, yellow-orange plaques of various size and shape. Histology shows that nevus sebaceous is a hamartoma consisting of epidermal, sebaceous, and apocrine elements. About 24% of nevi develop secondary tumors, some of which may be malignant (summary by Groesser et al., 2012).Also see giant pigmented hairy nevus (OMIM ) and malignant melanoma (OMIM ).

NEVUS, EPIDERMAL Is also known as nevus, keratinocytic, nonepidermolytic

• Autosomal dominant inheritance
• Global developmental delay
• Nevus
• Hyperkeratosis
• Palmoplantar keratoderma

SOURCES: OMIM NCIT MONDO

Medium match PINEAL HYPERPLASIA, INSULIN-RESISTANT DIABETES MELLITUS, AND SOMATIC ABNORMALITIES

Rabson-Mendenhall syndrome belongs to the group of extreme insulin-resistance syndromes (which also includes leprechaunism, the lipodystrophies, and the type A and B insulin resistance syndromes; see these terms).

PINEAL HYPERPLASIA, INSULIN-RESISTANT DIABETES MELLITUS, AND SOMATIC ABNORMALITIES Is also known as rabson-mendenhall syndrome, mendenhall syndrome;

• Autosomal recessive inheritance
• Global developmental delay
• Short stature
• Abnormal facial shape
• Neoplasm

SOURCES: NCIT UMLS OMIM MONDO SCTID ORPHANET GARD

Medium match PALMOPLANTAR KERATODERMA, MUTILATING, WITH PERIORIFICIAL KERATOTIC PLAQUES

Olmsted syndrome is a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques with severe pruritus of lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas (summary by Lin et al., 2012). The digital constriction ('pseudoainhum') may progress to autoamputation of fingers and toes (Olmsted, 1927).

PALMOPLANTAR KERATODERMA, MUTILATING, WITH PERIORIFICIAL KERATOTIC PLAQUES Is also known as olmsted syndrome;olms;mutilating palmoplantar hyperkeratosis with periorificial keratotic plaques; olmsted syndrome; palmoplantar and periorificial keratoderma

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment

SOURCES: OMIM UMLS ORPHANET MONDO

Medium match ACHONDROPLASIA, SEVERE, WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS; SADDAN

gene; 4p16.3).

ACHONDROPLASIA, SEVERE, WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS; SADDAN Is also known as saddan dysplasia;saddan

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

SOURCES: UMLS OMIM SCTID ORPHANET

Medium match LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 4; CGL4

Congenital generalized lipodystrophy type 4 combines the phenotype of classic Berardinelli-Seip lipodystrophy (OMIM ) with muscular dystrophy and cardiac conduction anomalies (Hayashi et al., 2009).For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (OMIM ).

LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 4; CGL4 Is also known as berardinelli-seip congenital lipodystrophy, type 4, with muscular dystrophy, lipodystrophy, berardinelli-seip congenital, type 4, with muscular dystrophy

• Autosomal recessive inheritance
• Global developmental delay
• Generalized hypotonia
• Scoliosis
• Failure to thrive

SOURCES: DOID ORPHANET OMIM GARD UMLS MESH MONDO

Medium match THANATOPHORIC DYSPLASIA, TYPE I; TD1

Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients with straight, relatively long femurs always had associated severe cloverleaf skull and were designated TD type II (TD2), while TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1) (Langer et al., 1987).

THANATOPHORIC DYSPLASIA, TYPE I; TD1 Is also known as thanatophoric dysplasia;td, thanatophoric dwarfism, platyspondylic lethal skeletal dysplasia, san diego type, lethal short-limbed platyspondylic dwarfism, san diego type;td1; thanatophoric dwarfism type 1

• Autosomal dominant inheritance
• Seizures
• Global developmental delay
• Hearing impairment
• Growth delay

SOURCES: MONDO OMIM NCIT UMLS ORPHANET GARD