Cryptorchidism, and Hypoglycemia

Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by an inability of the adrenal cortex to produce cortisol in response to stimulation by adrenocorticotropic hormone (ACTH). Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, hypoglycemia, convulsions, and shock. The disease is life-threatening if untreated (summary by Meimaridou et al., 2012).For a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (OMIM ).

• Seizures
• Neoplasm
• Failure to thrive
• Cryptorchidism
• Cardiomyopathy

SOURCES: OMIM MENDELIAN

Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary that is responsible for pituitary deficiency and is usually characterized by the triad of a very thin or interrupted pituitary stalk, an ectopic (or absent) posterior pituitary (EPP) and hypoplasia or aplasia of the anterior pituitary visible on MRI. In some patients the abnormality may be limited to EPP (also called ectopic neurohypophysis) or to an interrupted pituitary stalk.

PITUITARY STALK INTERRUPTION SYNDROME Is also known as psis|ectopic neurohypophysis

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Failure to thrive

SOURCES: ORPHANET MENDELIAN

Dilated cardiomyopathy with ataxia (DCMA) is characterized by severe early onset (before the age of three years) dilated cardiomyopathy (DCM) with conduction defects (long QT syndrome), non-progressive cerebellar ataxia, testicular dysgenesis, and 3-methylglutaconic aciduria.

DILATED CARDIOMYOPATHY WITH ATAXIA Is also known as mga5|dcma|3-methylglutaconic aciduria type 5|cardiomyopathy, dilated, with ataxia|mga, type v|dcma syndrome

• Intellectual disability
• Global developmental delay
• Ataxia
• Growth delay
• Failure to thrive

SOURCES: ORPHANET MESH OMIM MENDELIAN

Congenital adrenal hypoplasia (AHC) is a rare disorder that can be inherited in an X-linked or autosomal recessive (see {240200}) pattern. In X-linked AHC, primary adrenocortical failure occurs because the adrenal glands lack the permanent adult cortical zone. The remaining cells are termed 'cytomegalic' because they are larger than typical fetal adrenal cells (Hay et al., 1981; Reutens et al., 1999).Patients with AHC usually present in early infancy with primary adrenal failure. Hypogonadotropic hypogonadism (HHG) is a hallmark of the disorder, and is recognized during adolescence because of the absence or interruption of normal pubertal development. Abnormal spermatogenesis has also been observed in these patients. Milder forms of the disease have been described, with adrenal insufficiency sometimes occurring in childhood or even early adulthood. A few cases of partial HHG have been reported (summary by Raffin-Sanson et al., 2013). Transient precocious sexual development in infancy or early childhood can be a prominent feature of AHC (Landau et al., 2010).A contiguous gene syndrome involving a combination of congenital adrenal hypoplasia, glycerol kinase deficiency (OMIM ), and Duchenne muscular dystrophy (DMD ) is caused by deletion of multiple genes on chromosome Xp21 (see {300679}).

CYTOMEGALIC CONGENITAL ADRENAL HYPOPLASIA Is also known as ahch|cytomegalic adrenocortical hypoplasia|x-linked congenital adrenal hypoplasia|adrenal hypoplasia, congenital, with hypogonadotropic hypogonadism|ahc with isolated gonadotropin deficiency|addison disease, x-linked|ahx|ahc with hhg

• Global developmental delay
• Hearing impairment
• Failure to thrive
• Cryptorchidism
• Vomiting

SOURCES: OMIM ORPHANET MENDELIAN

Francke et al. (1987) noted that there are 3 clinically distinct forms of glycerol kinase deficiency: infantile, juvenile, and adult. The infantile form is associated with severe developmental delay, and those with the adult form have no symptoms and are often detected fortuitously.The infantile form of GK deficiency, or the 'GK complex,' results from the Xp21 contiguous gene deletion syndrome (OMIM ) with congenital adrenal hypoplasia (OMIM ) and/or Duchenne muscular dystrophy (DMD ), whereas the juvenile and adult forms have isolated GK deficiency (Walker et al., 1996).

GLYCEROL KINASE DEFICIENCY; GKD Is also known as gk deficiency|hyperglycerolemia|gk1 deficiency

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

SOURCES: OMIM ORPHANET MENDELIAN

Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency is a very rare form of congenital adrenal hyperplasia (CAH; see this term) encompassing salt-wasting and non-salt wasting forms with a wide variety of symptoms, including glucocorticoid deficiency and male undervirilization manifesting as a micropenis to severe perineoscrotal hypospadias.

CONGENITAL ADRENAL HYPERPLASIA DUE TO 3-BETA-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY Is also known as cah due to 3-beta-hydroxysteroid dehydrogenase deficiency

• Cryptorchidism
• Feeding difficulties
• Vomiting
• Hypospadias
• Delayed skeletal maturation

SOURCES: ORPHANET MENDELIAN

Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency is a rare, genetic, chronic, primary adrenal insufficiency disorder, due to partial loss-of-function CYP11A1 mutations, characterized by early-onset adrenal insufficiency without associated abnormal external male genitalia. Patients present with signs of adrenal crisis, including electrolite abnormalities, severe weakness, recurrent vomiting and seizures. Ultrasound reveals absent (or very small) adrenal glands.

• Failure to thrive
• Cryptorchidism
• Feeding difficulties
• Vomiting
• Delayed skeletal maturation

SOURCES: ORPHANET MENDELIAN

• Seizures
• Neoplasm
• Muscle weakness
• Cleft palate
• Cryptorchidism

SOURCES: ORPHANET MENDELIAN

Webb-Dattani syndrome is an autosomal recessive disorder characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency due to hypoplastic development of these brain regions. Patients present soon after birth with multiple pituitary hormonal deficiencies and subsequently develop microcephaly, seizures, and spasticity. Other features include postretinal blindness and renal abnormalities (summary by Webb et al., 2013).

WEBB-DATTANI SYNDROME; WEDAS Is also known as hypothalamo-pituitary-frontotemporal hypoplasia with visual and renal anomalies

• Seizures
• Global developmental delay
• Microcephaly
• Growth delay
• Cryptorchidism

SOURCES: OMIM ORPHANET MENDELIAN

Bilateral renal agenesis is the most profound form of renal agenesis (see this term), characterized by complete absence of kidney development, absent ureters and subsequent absence of fetal renal function resulting in Potter sequence with pulmonary hypoplasia related to oligohydramnios, which is fatal shortly after birth.

RENAL AGENESIS, BILATERAL Is also known as renal aplasia|renal adysplasia|hereditary renal aplasia|renal agenesis|hra

• Hypertelorism
• Abnormal facial shape
• Cleft palate
• Cryptorchidism
• Low-set ears

SOURCES: OMIM ORPHANET MENDELIAN